key: cord-015324-y44sfr0c
authors: nan
title: Scientific Programme
date: 2007-09-01
journal: Pediatr Nephrol
DOI: 10.1007/s00467-007-0558-3
sha: 
doc_id: 15324
cord_uid: y44sfr0c

nan

The kidney plays an important role in ion homeostasis in the human body. Several hereditary disorders characterized by perturbations of renal magnesium reabsorption leading to hypomagnesemia were described over the past 50 years. Only recently, mutations in renal ion channels and transporters have been identified in several of these diseases, following positional cloning strategies in families with these disorders. Muations in the SLC12A3 gene have been identified in patients with Gitelman syndrome, an autosomal recessive disorders characterized by hypokalemia, hypomagnesemia and hypocalciuria. SLC12A3 encodes the thiazide-sensitive Na + , Cl-cotransporter (NCC) in the distal convoluted tubule (DCT), the nephron site of active renal magnesium reabsorption. The hypomagnesemia in Gitelman syndrome has been shown to be secondary to the primary defect in NCC. Mutations in the FXYD2 gene have been found in patients with autosomal dominant renal hypomagnesemia associated with hypocalciuria (IDH). FXYD2 encodes the gamma-subunit of the Na + , K + -ATPase, which is expressed primarily in the kidney with the highest expression levels in DCT and TAL. Hypomagnesemia in patients with IDH can be severe (<0.40 mM) and cause generalized convulsions. The molecular mechanism for renal Mg 2+ loss in this autosomal dominant type of primary hypomagnesemia remains to be elucidated. In patients with autosomal recessive hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) mutations in the CLDN16 gene, and very recently also in the CLDN19 gene, have been identified. These genes encode CLaudin16 and Claudin19 respectively, which are essential components of the paracellular pathway for magnesium at the level of the thick ascending limb of Henle's loop. Mutations in TRPM6, encoding the epithelial Mg 2+ channel TRPM6 in the apical membrane of DCT cells, have been identified in patients with Mg 2+ wasting and secondary hypocalcemia (HSH). This autosomal recessive disease is due to defective intestinal and renal Mg 2+ (re)absorption, and affected individuals show neurologic symptoms of hypomagnesemic hypocalcemia, including seizures and muscle spasms during infancy.

In my lecture, I will give an update on the proteins involved in magnesium reabsorption and the emerging pathophysiological understanding of hereditary disorders in which renal handling of this divalent ion is disturbed.

Transcriptional control of genes that regulate tissue patterning and the cell cycle is fundamental to normal renal development. The mammalian kidney arises from reciprocal inductive tissue interactions between the ureteric bud and the metanephric mesenchyme. These interactions result in growth and branching of the ureteric bud and its daughter collecting ducts, a process termed, renal branching morphogenesis, and formation of nephrogenic progenitors and mature nephrons. Expression and activity of transcription factors in ureteric and metanephric mesenchyme cells determines the patterning of ureteric bud and metanephric mesenchyme derived tissue elements. This lecture will highlight transcription factors critical to renal branching morphogenesis and nephrogenesis, with particular emphasis on those factors that are mutated in humans with renal malformation. The regulation of transcription factor activity will be discussed in the context of growth factor signaling pathways downstream of WNTS, Bone Morphogenetic Proteins and Sonic Hedgehog and pathways such as NOTCH that control cell differentiation. The complexity of transcriptional signaling will be highlighted in the normal and malformed kidney at the level of transcriptional factor interactions and target gene promoters that can be targeted by mutiple signaling pathways.

T. Benzing

Diseases of the glomerular filter of the kidney are a leading cause of end-stage renal failure. Recent studies have emphasized the critical role of the slit diaphragm of podocytes for the size-selective filtration barrier of the kidney and revealed novel aspects of the mechanisms leading to proteinuria, both in inherited and acquired diseases. Several critical structural protein components of the slit diaphragm have been identified. Recently, it has been shown that slit diaphragm proteins, in addition to their structural functions, participate in common signaling pathways. This talk will focus on what is known about the importance of the podocyte for the function of the glomerular filter of the kidney. It will provide a snapshot of our current understanding of the signaling properties of slit diaphragm proteins and project a framework for further studies necessary to delineate the function and dynamics of the slit diaphragm protein complex and the pathogenesis of nephrotic syndrome.

Long-term survival of children with end-stage renal disease (ESRD) has increased in the last 20 years but the mortality rate remains high. Cardiovascular disease accounts for 40 to 50% of all deaths, infectious disease about 20%. A prolonged period of dialysis versus having a renal graft and persistent hypertension are mortality risk factors. The prevalence of all sorts of morbidities is high among those who have reached adulthood. Nearly 50% of all these patients suffer from left ventricular hypertrophy and life threatening vascular changes; nearly one third has clinical signs of metabolic bone disease. This accounts for both dialysis and transplanted patients. The chance of getting cancer is 10 times increased as compared to the general population; skin cancer and Non-Hodgkin lymphomas are most reported. A long period of dialysis at childhood is associated with impairment of both cognitive and educational attainment in adulthood. Yet, despite all these negative outcomes, the health perception of young adults with childhood onset ESRD is good. Unemployment under young adults on chronic dialysis with pediatric onset of disease is higher than among healthy age related peers, but much lower than among dialysis patients of the same age with adult onset of disease. An impaired social development in childhood is associated with an impaired mental health perception at adult age. Research and therapy in children with ESRD should focus not only on prevention of graft failure but also on prevention of co-morbidity, especially cardiovascular disease, life threatening infections and malignancies. Early transplantation, more extended forms of frequent hemodialysis in those who can not be transplanted, a more rigorous treatment of hypertension, avoidance of calcium-containing phosphate binders, reduction of the chronic inflammatory state, and tailor made anti-rejection therapy after transplantation may all be targets to improve outcome in future patients. Psychosocial care should be more focused on attainment of independency and preparation for adult life, i. e. schooling and job career.

Applying Regenerative Medicine to Combat Organ Shortage

Laboratory of Regenerative Nephrology, Edmond and Lili Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Organ transplantation has been one of the major medical advances of the past 30 years; however, it is becoming increasingly apparent that the supply of organs is limited and will not improve with current medical practice. Regenerative medicine is focused on the development of cells and tissues for the purpose of restoring function through transplantation. When facing late stages of ESRD, which necessitate whole kidney transplantation, organogenesis represents an alternative to combat organ shortage. Indeed, previous data pinpoints a window of time in human and pig kidney organogenesis that may be optimal for transplantation into mature recipients. "Window" transplants are defined by their remarkable ability to grow, differentiate and undergo vascularization, achieving successful organogenesis of urine-producing miniature kidneys with no evidence of trans-differentiation into non-renal cell types, lack of tumorigenicity and reduced immunogenicity compared to adult counterparts. In contrast, when dealing with earlier stages of ESRD or acute renal disease, which allow for individual cell replacement, both bonemarrow derived and kidney specific stem cells, might be applicable. Accordingly, we show in proof-of-principle experiments that a novel population of multi-potential stem cells derived from the adult murine kidney are capable of re-populating ischemically injured tubular cells, while hematopoietic stem cells (CD34+CD133+) or hemangioblastic progenitor cells can give rise to peritubular endothelial cells. Thus, different types of biological materials (embryonic kidney, adult kidney, adult bone marrow) offer new and powerful strategies for future tissue development and regeneration in renal medicine.

K. Tory, É. Kis, A. Szabó, G. Reusz 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary It is well known that chronic renal failure significantly increases the risk of cardiovascular mortality in adults. Transplantation decreases this risk; however, it still exceeds that of the normal population.

As the number of children on renal replacement therapy (including transplantation) has significantly increased in recent years, there has been a growing amount of evidence regarding the increased cardiovascular vulnerability of this specific patient group. One important factor of cardiovascular mortality in adults is the dysfunction of the autonomic nervous system, previously designated as autonomic neuropathy. In a series of studies using the conventional Ewing tests as well as heart rate variability (HRV) monitoring we were able to show altered sympathovagal balance in children on peritoneal-and hemodialysis, that was at least partly reversible following renal transplantation. According to our data sympathetic overactivity plays a major role in the sympathovagal disequilibrium observed. Correspondingly, beta-adrenergic blockade improves the decreased HRV in the young. Early, accelerated arteriosclerosis is another important, recently recognized consequence of CRF in children. Arterial calcification leads to increased arterial stiffness deteriorating the cushioning function of the aorta. Arterial stiffness can be assessed by the reproducible and non-invasive measurement of the pulse wave velocity (PWV). In adults, it was found to be a strong, independent predictor of cardiovascular mortality. Hypertension, hyperphosphatemia/elevated serum calciumphosphate product and vitamin D deficiency are the principal factors associated with PWV. Recently, PWV was also shown to be increased in children on dialysis. However, the difference to the normal population may only be apparent if a control group matched for body dimensions is used, because of the dependence of PWV on body dimensions and uremic children's significant growth deficit. Furthermore, increased PWV could also be shown in children following renal transplantation (TX) indicating the persistence of these lesions even following successful TX. The data on the autonomic nervous system and arterial dysfunction in young patients point to the necessity of early prevention in order to avoid the cardiovascular complications of CRF. This study was supported by grants OTKA-T046155-F048842-F042563 and ETT 435/2006.

Nitric oxide (NO) production is reduced in CKD due to decreased renal and widespread decreases in endothelial NO production. Possible causes of NO deficiency are: 1). substrate (L-arginine) limitation; 2). Increased levels of circulating endogenous inhibitors of nitric oxide synthase (particularly asymmetric dimethylarginine [ADMA]); 3). Decreased NOS protein abundance/activity. Decreased L-arginine availability in CKD is likely due to perturbed renal biosynthesis secondary to damage to the renal parenchyma. In addition, inhibition of transport of Larginine into endothelial cells and shunting of L-arginine into other metabolic pathways (e. g. arginase) will also decrease availability. Elevated plasma and tissue levels of ADMA in CKD are functions of reduced renal excretion (minor), reduced catabolism by dimethylarginine dimethylamino-hydrolase (DDAH) and possibly increased protein methylation. An increase in ADMA has emerged as a major independent risk factor in many forms of cardiovascular disease as well as end-stage renal disease (and probably CKD). Decreased renal NOS protein abundance and activity have been reported by us in multiple models of CKD in the rat. The neuronal (NOS 1) isoform is always reduced in the presence of injury, and is preserved in settings where there is protection from damage (female; Wistar Furth rat vs. Sprague Dawley). Generalized and nNOS specific inhibition accelerates underlying renal injury and in vulnerable animals will cause injury in the absence of underlying renal disease. We also find that relaxin (RLX) mediated prevention and repair of damaged kidneys requires an intact NO system in order to function. In summary, NO deficiency can cause cardiovascular and renal disease, and CKD results in NO deficiency, contributing to a vicious cycle that promotes progression. An intact NO system is required for RLXmediated repair of kidney damage. NO deficiency in CKD is likely due to many causes: Decreased arginine synthesis/availability and transport; increased endogenous ADMA functioning as competitive inhibitor; decreased enzyme abundance and activity will all lead to reduction in NO generation. In addition, the oxidative stress of CKD will further reduce NOS activity, switch the NOS to become oxidant generators and will scavenge NO to form the harmful peroxynitrite.

Selected glomerulopathies due to single gene defects such as Finnish type nephropathy, diffuse mesangial sclerosis Alport/thin membrane disease and inherited lipid disorders and will be discussed. Finnish nephropathy is due to mutations of Nephrin, a major structural component of the slit diaphragm. Over 50 Nephrin mutations are known associated with variably absent slit diaphragms, originally thought to be specific for constitutional Nephrin mutations. However, sporadic minimal change disease and membranous glomerulonephritis may have absent slit diaphragms suggesting that Nephrin may participate in the nephrotic syndrome in nonhereditary diseases. DMS is one cause of congenital nephrotic syndrome, characterized by podocyte proliferationis shared by WT1 (Denys-Drash syndrome), Laminin α2 (Pierson syndrome) and Galloway-Mowat syndrome mutations. Alport nephritis is a paradigm in which only a subset of mutations may predict disease severity (COL IVα5)). Heterozygous Alport is similar to thin membrane disease (TMD), but 25% of TMD harbor COL (IV) α3 mutations and a subset has COL IVα2. Nail Patella syndrome due to heterozygous loss of LMX1B gene which regulates COL IVα3-5 expression during kidney development. In classic Nail-Patella pathology fibrillar collagen bundles within the GBM are identical in severe and mild disease. Thus the mutation does not correlate with prognosis. A mutation overlap in Factor H gene in lipid disorders such as dense deposit disease (DDD) and LCAT underscores glomerular pathologies that ranges from classic ribbon-like deposits in DDD, to lucent GBM deposits characteristic of LCAT, or subendothelial lipid pools in lipoprotein glomerulopathy. The importance of genetics underscoring the pathology is amply demonstrated but mutations may not determine prognosis. Background genes, post-translational modification and or protein/protein interactions in podocytes or the GBM may act as phenotypic modifiers.

Acute renal failure (ARF) has many different definitions. RIFLE criteria distinguish "risk, injury, failure, loss and end-stage renal disease" features of this event. Classic forms include pathophysiological cases of renal hypoperfusion and direct parenchymal injury, as well as postrenal anatomical obstruction. Microvascular mechanism is in general the effect of disturbed balance between vasoconstriction (in response to endothelin, angiotensin II, thromboxane A2, leukotrienes and increased sympathetic nerve activity) and vasodilatation (in response to nitric oxide, PGE2 and bradykinin). Endothelial and vascular smooth muscles cells may undergo structural damage and increased leukocytes-endothelial adhesion is a cause of inflammation. Cytoskeletal breakdown, loss of polarity, apoptosis, necrosis, desquamation of viable and necrotic cells with tubular obstruction are underlying mechanisms of acute tubular necrosis. Ischemic and direct tubular injury dominate as causes of ARF, however specific epidemiology is strictly age-related. Sepsis and major surgeryrelated events are the most common causes of ARF in hospitalized patients. Data on genetic background of certain genes polymorphisms and susceptibility to specific risk factors in newborns and infants are conflicting. Several prophylactic and therapeutic techniques are available, however not of universal value. Appropriate fluid management is crucial in ischemic ARF, classic hemolyticuremic syndrome and rhabdomyolysis, however fluid overload is the one of major predictors of poor outcome in children admitted to ICU. Neither "renal dose" of dopamine, nor loop diuretics change the outcome. Involvement of extrarenal organs worsens the overall outcome, which is the poorest in patients with multi-organ failure. Early introduced renal replacement therapy is one of the key modalities in ICU-treated patients. Continuous techniques are of major value. In specific cases, such as hepato-renal syndrome, albumin ("liver") dialysis serves as an effective bridge to liver transplantation.

Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare recessively inherited disease, manifested by persistent severe hyperphosphatemia and self-remitting episodic bone pain with radiologic findings of periosteal reaction and cortical hyperostosis. Hyperphosphatemia in this patient population is not counter-balanced by PTH or vitamin D, posing a mirror image of two hypophosphatemic states which result from increased activity of fibroblast growth factor 23 (FGF23). The two hypophosphatemic disorders which result from enhanced urinary phosphate leak are: dominantly inherited hypophosphatemic rickets and tumor induced osteomalacia. This observation was the impetus to study the role of FGF23 in HHS. Affected individuals were found to have low levels of the full length, biologically active FGF23, but markedly augmented amounts of the cleaved inactive fragments. Patients were found to be homozygous for a mutation in the GALNT3 gene encoding a peptide involved in mucin-type O-glycosylation. Decreasing the expression of the GALNT3 gene by RNA interference resulted in augmenting processing of the intact FGF23. Our research indicates that the primary defect in HHS is a state of underglycosylation of FGF-23 resulting from reduced expression of ppGaNTase-T3, due to mutations in GALNT3, and leading to augmented processing at the cleavage site. These changes in FGF-23 would abolish its phosphaturic effect and lead to severe persistent hyperphosphatemia. This study provides the pathogenetic mechanism of the first mucin-type O-glycosylation defect identified. Our observation lends further credence to the primary and essential role of FGF23 in phosphate homeostasis through a PTH-independent pathway. This was substantiated most recently by several reports which showed that mutations in the FGF23 gene are responsible for familial hyperphosphatemic tumoral calcinosis (FHTC) . A further study showed that HHS and familial hyperphosphatemic tumoral calcinosis are allelic disorders with a founder mutation in our region.

Immune responses govern the outcome of many forms of chronic kidney disease. Gene therapy offers the potential to modify immune genes to improve outcome. We will discuss the potential use of gene transduction as a therapy for chronic kidney disease. Background: Chronic proteinuric renal disease is a major cause of end stage renal disease in man. Adriamycin nephropathy is a murine model of chronic proteinuric renal disease where initial chemical injury is followed by immune and structural changes that mimic human disease. Foxp3 is a gene specifically expressed by regulatory T (Treg) cells. Forced expression of the gene Foxp3 causes transduced T cells to develop a regulatory phenotype. We hypothesised that FoxP3 transduced regulatory T cells could protect against renal injury in Adriamycin nephropathy. Methods: The retroviral vectors expressing Foxp3 and green fluorescent protein (GFP) (Foxp3/MIGR) and GFP alone (MIGR) were transfected into package cell lines EcoPack2-293, which produced the two retroviruses. CD4+ T cells were isolated from spleen of Balb/c mice and stimulated by anti-CD3 mAb and IL-2 for 24 hours and then were infected with either retrovirus. Expression was confirmed and phenotypic and in vitro functional assays demonstrated a regulatory phenotype. One week after infection, the GFP+ positive cells were sorted. Foxp3 and control vector (MIGR) transduced T cells were administered to Adriamycin (ADR)-induced progressive renal nephropathy in mice. Results: Adoptive transfer of the Foxp3 transduced T cells protected against renal injury. Urinary protein excretion was reduced; there was less renal injury as measured by glomerulosclerosis, and interstitial infiltrates. Serum creatinine, glomerular sclerosis and tubulointerstitial alterations were significantly lower in ADR-Foxp3 group, compared to those without treatment (ADR) and treated with control vector (MIGR) transduced group (ADR+MIGR). The Foxp3 transduced CD4 T cells also showed suppressive activity in vitro. We conclude that Foxp3 induced T reg cells may have a therapeutic role in protecting against immune injury and disease progression in chronic proteinuric renal disease.

The ItalKid Project is a prospective, population-based registry that was started in 1990. Prevalent and incident cases of chronic renal insufficiency (CRI) in children and adolescents were identified throughout Italy (total population base: 16.8 million children). The inclusion criteria were: i) creatinine clearance (Ccr): <90ml/min/1.73m 2 bsa; and ii) an age of <20 years at the time of registration. As to December 31st, 2006 a total of 2026 patients had been registered. The incidence of CRI was estimated 12.1 cases per million and the (point) prevalence 74.7 per million of the age-related population (marp). The probability of kidney survival at 20 years of age was significantly different depending on the Ccr at study entry, being 63% in patients with mild renal insufficiency (Ccr 51-75 ml/min), 30% in those with moderate renal insufficiency (Ccr 25-50 ml/min) and 3% in those with severe renal insufficiency (Ccr <25 ml/min). The patients with normal (<0.2) and low (0.2-1.0) uPr/uCr compared to those with mild (>1.0), showed a significantly slower decline in Ccr (DeltaCcr +0.2±3.62 and -0.6±3.67 vs -3.76±5.64 ml/min/yr) and a higher kidney survival (96.7 and 94.1 vs 44.9%). The incidence of renal replacement therapy (RRT) was 7.3/year/100 patients and the casefatality rate on conservative treatment 1.41%. Patients showed a significantly different slope of Ccr before pubertal growth spurt as compared to after: -0.31±4.02 mL/min/1.73mq/yrs and -3.1±5.04. A non-linear pattern of decline in the probability of kidney survival, with a steep decrease during pubertal and early post-pubertal age was observed: the overall probability of RRT at age 10 was estimated 9.4%, while 51.8% of the patients will eventually required RRT before the 2nd decade of life was over. suggesting that pubertal development triggers the progression of CRI in children. Treatment with angiotensin converting enzyme inhibitors did not significantly modify the naturally progressive course of hypodysplastic nephropathy.

Ambulatory blood pressure monitoring (ABPM) is a relatively new technique of blood pressure assessment in children and adolescents that offers several distinct advantages over traditional methods of blood pressure measurement, including the ability to detect white coat and masked hypertension, as well as the ability to assess nocturnal blood pressure. The role of ABPM in the diagnostic evaluation of pediatric patients with elevated blood pressure is well-established, and recent surveys have demonstrated that it is used quite often by pediatric nephrologists and other practitioners during the initial evaluation of elevated blood pressure. It is less well-established, however, what role ABPM might play in hypertensive children and adolescents once hypertension has been diagnosed and treatment initiated. Studies in adults have demonstrated that ABPM can assess whether patients on antihypertensive medications have achieved goal blood pressure, or whether their hypertension has progressed in severity. ABPM can be used to follow nocturnal blood pressure in patients with chronic kidney disease (CKD) and diabetes, facilitating early identification of non-dipping, which is a known risk factor for progression of CKD or development of diabetic nephropathy, respectively. ABPM can also be incorporated into clinical trials of antihypertensive medications to help assess their efficacy and safety. While additional data supporting these applications of ABPM to pediatric hypertension clearly need to be generated from well-designed clinical trials, we propose that there is ample justification to utilize ABPM just as frequently after the diagnosis of hypertension as before.

Childhood obesity is increasing globally in epidemic proportions and affects children in both industrialized and non-industrialized nations. In the last 30 years the percentage of overweight or obese children has increased from 5% to almost 30%. If current trends continue, as many as 50% of children may be overweight or obese by the year 2010. Obesity predisposes to development of the metabolic syndrome, which is defined in children as the presence of three or more of the following features: abdominal adiposity (BMI >95%ile), serum triglycerides >95%ile, serum HDL cholesterol <5% ile, fasting blood glucose >110 mg/dL, and/or hypertension (systolic or diastolic blood pressure >95%ile adjusted for age, gender and height). The metabolic syndrome occurs in about 5% of children, but in 30-50% of overweight children. The presence of the metabolic syndrome increases the risk for cardiovascular disease and chronic kidney disease almost ten-fold in adults. Adipose tissue does not just store fat, but also has important endocrine and immune functions mediated through adipocytokines, including leptin, adiponectin, resistin, apelin and visfatin, and classical cytokines such as TNF-a and IL-6. Increased leptin, decreased adiponectin and increased inflammatory cytokines, which occur in obesity, are known to induce vascular endothelial dysfunction and increase blood pressure. Increase in adipose tissue also leads to infiltration by monocytes, macrophages and lymphocytes, which are stimulated to produce additional cytokines that may contribute to the systemic inflammation associated with obesity and vascular inflammation associated with hypertension. Screening for hypertension and metabolic syndrome in obese children is critical to allow early identification of the metabolic syndrome and aggressive early intervention to reduce the risks for progression to cardiovascular disease and chronic kidney disease in later life. Therapeutic strategies must include lifestyle changes of weight loss, healthier diet and regular physical exercise as well as treatment of hypertension, hyperlipidemia or hyperglycemia. Blood pressure (BP) regulation is affected by numerous physiologic, biochemical, genetic and environmental factors. It has been suggested that exogenous conditions affecting intra-uterine growth and development may pre-program individuals for hypertension, metabolic abnormalities and cardiovascular morbidity in later life. Animal data and human autopsy findings support a link between intrauterine growth, nephron endowment and postnatal hypertension. Conceptually, it appears increasingly unclear whether the association of birth weight and BP in later life is mediated by intrauterine growth retardation as suggested by various animal models, whether prematurity per se affects BP programming independent of the fetus, nutritional status, or whether postnatal circumstances statistically linked to low birth weight affect this relationship. We have designed a study to evaluate the relationship between gestational age, birth weight and BP abnormalities by applying ABPM in a group of children born preterm with and without intrauterine growth retardation and a local control group of children born at term with appropriate weight. This study represents the first systematic assessment of 24-hour cardiovascular regulation in children and adolescents born preterm. Our findings indicate that a fraction of these preterm born subjects has a selective nocturnal increase in systolic BP, resulting in an elevated prevalence of non-dipping. Our analysis suggests that intrauterine growth retardation, rather than prematurity per se, is the major effector of the early cardiovascular abnormalities observed in preterm children. Moreover, we have found that nocturnal systolic BP was closely linked to heart rate, pointing to a possible role of sympathetic hyperactivation. While little data is available regarding a link between low birth weight and/or prematurity and sympathoadrenal function in adult humans, a role of the sympathetic nervous system in the programming of adult hypertension has been consistently demonstrated in various animal models of fetal growth retardation.

In conclusion, we detected subtle abnormalities of circadian BP regulation in those preterm born children who suffered from intrauterine growth retardation and this may reflect sympathetic hyperactivation.

The intrinsic tendency of kidney disorders with reduced nephron mass to progress and the quest for renoprotective strategies are an ongoing focus of renal research. In adults, hypertension is not only a marker but also a major driving force of renal failure progression. Renin-angiotensin system blockers (ACE inhibitors and AT1 receptor blockers) are preferred antihypertensive drugs in CKD due to their specific renoprotective effects beyond blood pressure (BP) control, mediated by their antiproteinuric, antiinflammatory and antifibrotic properties. It is less clear whether BP reduction to low-normal values has an additional salutory effect on GFR preservation. Children suffer from a markedly different spectrum of renal diseases than adults, with a preponderance of hypo/dysplastic kidney malformations. Hypertension and proteinuria are common but usually moderate.

To elucidate the renoprotective efficacy of ACE inhibition and strict BP control in children, the ESCAPE trial was launched by a consortium of 33 European pediatric nephrologists. A total of 400 children and adolescents with stage II-IV CKD received a fixed dose of ramipril and were randomized to intensified (<50th percentile) or conventional BP control (50th-95th pct). 24 h-BP, proteinuria and GFR were monitored over a 5-year period. 24 h mean arterial pressure (MAP) was reduced by ramipril from 89 to 83 mm Hg (i. e. from 1.5 to 0 SDS) on average. Subsequently, mean MAP was lowered further to 79 mm Hg at 24 months in the intensified arm, and maintained around 83 mm Hg (0.2 SDS) in the conventional control arm (p<0.0001). On average 1.1 antihypertensive drugs were added to ramipril in the intensified and 0.4 in the conventional treatment arm (p=0.0001). Treatment tolerability was excellent in both arms, with less than 3% dropouts due to side effects. In summary, ramipril was effective and well tolerated in children with CKD. It is possible and safe to target low-normal BP in children. Final results regarding renal survival will be available in summer 2007 and presented at the IPNA meeting.

Nephronophthisis and Joubert Syndrome: Converging on Convergent Extension?

Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to terminal kidney failure in adolescence. NPHP may be associated with retinitis pigmentosa (RP) in Senior-Loken syndrome (SLSN) or with cerebellar vermis aplasia in Joubert syndrome (JBTS). We have identified by positional cloning 7 genes as mutated in NPHP. The gene product of NPHP1, nephrocystin-1, acts in focal adhesion signaling. By positional cloning we detected mutations in the NPHP2/inversin gene as causing infantile NPHP (type 2) with association of situs inversus or RP. We demonstrated expression of NPHP1, 2 in primary cilia of renal epithelial cells, supporting a new unifying theory for the pathogenesis of cystic kidney diseases (Watnick et al. Nature Genet 34: 355, 2003) , stating that the products of all genes mutated in cystic kidney disease in humans, mice, or zebrafish are expressed in primary cilia, basal bodies, or centrosomes of renal epithelial cells (Hildebrandt et al. Nature Rev Genet 6: 928, 2005) . Identification of NPHP3 mutations in NPHP type 3 also revealed the cause of the renal cystic disease mouse model "pcy", for which treatment has been demonstrated. Positional cloning of NPHP4 led to the demonstration that its gene product, nephrocystin-4, is conserved in C. elegans and expressed together with nephrocystin-1 in ciliated head and tail neurons of the nematode. The role of primary cilia function for retinal-renal syndromes was confirmed by identification of the novel NPHP5 gene. Recently, several signaling pathways have been implicated in the downstream signaling pathways that connect ciliary/basal body function to the renal cystic phenotype. These include the Wnt signaling/planar cell polarity pathways, and the hedgehog signaling pathway. We implicated the planar cell polarity signaling pathway in NPHP by positional cloning of mutations in the gene NPHP6/CEP290 as causing Joubert syndrome. Abrogation of nphp6 function in zebrafish caused planar cell polarity (convergent extension) defects and recapitulated the human phenotype of Joubert syndrome. Further gene identification in NPHP will result in the definition of functional networks of primary cilia, centrosomes, and planar cell polarity as they pertain to the pathogenic mechanisms of NPHPassociated syndromes and other cystic kidney diseases. HNF1b is a transcription factor that is expressed in bile ducts, intestine, pancreas and renal epithelia. Germ-line inactivation of the mouse HNF1β/Tcf2 gene is embryonic lethal (E7.5) due to defective differentiation of the extra-embryonic visceral endoderm. HNF1β is later expressed in endoderm derivatives and in the mesonephros. To understand the function of HNF1b at later stages of development and during organogenesis, we applied a conditional inactivation based on a (Cre-LoxP) strategy. With the use of a CRE recombinase that is expressed in renal collecting ducts and Henle loops (KSP-CRE) we found that HNF1b inactivation leads to Polycystic Kidney Disease (PKD). This is reminiscent of the renal phenotype of patients carrying heterozygous mutations in TCF2/HNF1β. These patients suffer from Maturity Onset Diabetes of the Young type 5 (MODY5) and at the same time from Renal Cysts (Renal Cysts and Diabetes or RCAD). This cystic phenotype is linked to the defective expression of PKHD1 and PKD2, two genes mutated in PKD patients. The cellular and molecular mechanisms underlying PKD are still poorly understood. It was recently speculated that planar-cell-polarity signalling (wnt) could be at the basis of cyst formation. Maturation of nephrons during development is accompanied by a considerable lengthening of tubules. This process involves an intense proliferative phase without any increase in tubule diameter. Interestingly, we discovered that the progeny of consecutive cell divisions are adjacent one another and oriented in parallel to the axis of tubules. This suggested that upon lengthening, cells divide according the tubule axis. In addition, 3D image reconstructions revealed that oriented cell division is due to the alignment of the mitotic spindle with the axis of the tubule. We hypothesized that oriented cell division could play an essential role in preventing tubular dilation during the massive proliferative phase that accompanies tubular elongation. Indeed, our results indicated that both in KSP-CRE-kidney-specific-HNF1β-deficient pups and in the PCK rats, lacking the expression of PKHD1, the mitotic alignments were highly distorted. Our results indicate that HNF1β plays a crucial role in activating the expression of genes involved in the control of tubular size maintenance during tubular elongation.

Emerging evidence suggests that the intravenous injection of bone marrow-derived cells improves renal function after acute tubular injury. Examination of human transplant biopsies of female kidneys that had been transplanted into male recipients have shown the presence of tubular cells that co-express the Y chromosome and epithelial markers. However, controversy exists as to whether the protective effect is due to engraftment of the cells in the injured tubule or an endocrine/paracrine effect of the injected cells. Our studies demonstrate that intravenous infusion of whole bone marrow from male mice into female recipients results in the appearance of significant numbers of Y chromosome + cells in the kidney interstitium, and rare Y chromosome + cells in the tubules. The majority of the interstitial cells express leukocyte markers such as CD45. In addition, we have found that i. v. or i. p. injection of bone marrow stromal cells (MSC, adherent non-hematopoietic marrow cells) into mice reduced the severity of cisplatin-or ischemia-induced AKI. Examination of these kidneys demonstrates that MSCs enhance tubular cell proliferation and decrease tubular apoptosis after injury. Examination of multiple tissue sections at 1 or 7 days after injury failed to reveal any examples of Y chromosome cells within the tubules, and only rare examples of Y chromosome cells within the renal interstitium. Furthermore, exposure to conditioned medium from cultured MSCs (MSC-CM) significantly diminished cisplatin-induced death of cultured proximal tubule cells in vitro, while i. p. administration of MSC-CM in the mouse markedly diminished the rise in BUN associated with cisplatin injection. Thus our data suggests that hematopoietic cells and their derivatives from adult bone marrow enter the kidney in response to injury where they are primarily localized to the interstitial space as inflammatory cells. In rare instances, these cells may differentiate into, or fuse with, tubular epithelial cells. In contrast, bone marrow MSCs fail to enter the kidney in significant numbers, but can protect the endogenous tubular cells from toxic injury by secreting a factor or factors that limit apoptosis and enhance proliferation. Renal hypodysplasia (RHD) is characterized by a reduced nephron number, small kidney size and disorganized renal tissue. A hereditary basis has been established for a subset of affected patients, suggesting a major role of developmental genes involved in early kidney organogenesis. Gene mutations with dominant inheritance causing RHD, urinary tract anomalies and defined extrarenal symptoms have been identified in TCF2 (Renal Cysts And Diabetes syndrome (RCAD)), PAX2 (Renal-Coloboma syndrome (RCS)), EYA1 and SIX1 (Branchio-Oto-Renal syndrome (BOR)) for the most frequent of these syndromes. A recent study on a cohort of 100 patients with RHD and consecutive renal insufficiency demonstrated that 16% of them had mutations in one gene encoding for a transcription factor. The majority of mutations were identified in TCF2 (HNF1β) (especially in the subset with kidney cysts) and PAX2. This study demonstrates that subtle extrarenal symptoms in syndromal RHD easily can be missed. Genetic testing in children with RHD should be preceded by a thorough clinical evaluation for extrarenal symptoms, including eye, ear, and metabolic anomalies. The presence of these anomalies increases the likelihood of detecting a specific genetic abnormality. In addition, mutations in genes that are usually associated with syndromes can occur in patients with isolated RHD. The RET receptor, its ligand GDNF and the co-receptor GFRa1 play a pivotal role during early nephrogenesis and enteric nervous development. In humans, activating RET mutations cause multiple endocrine neoplasia, whereas inactivating mutations lead to Hirschsprung disease. While RET deficiency also causes renal hypodysplasia (RHD) in the mouse model, genetic abnormalities in RET have not been characterized in human isolated renal malformations to date. The RET mutations, Y971F and S649L, reportedly predisposing to medullary thyroid carcinoma (MTC) were found in one and six patients respectively in the same RHD cohort. None of the patients or their carrier relatives had clinical evidence of MTC at the time of the study. Our findings suggest that RET mutations predispose to both MTC and RHD, with a low penetrance for either disorder. Interestingly, a GDNF mutation was found in addition to a RET mutation and to an EYA1 mutation in a patient with the branchio-oto-renal syndrome suggesting an oligogenic inheritance.

Mutations in CLCN5, the gene encoding the chloride/proton exchanger ClC-5, underlie most forms of Dent's disease, an X-linked nephrolithiasis syndrome that is always associated with low molecular weight proteinuria. ClC-5 belongs to the CLC gene family of chloride channels and transporters and, in addition to other sites, is expressed in apical endosomes of the proximal tubule. In these vesicles, it co-localizes with the proton pump and with endocytosed proteins. Previously thought to be a Clchannel, it is now known to mediate electrogenic Cl -/H + -exchange. This notion remains compatible with a role in supporting the acidification of endosomes by providing an electrical shunt for the H + -ATPase. To clarify the pathogenesis of Dent's disease, we created a knock-out mouse model. It displayed low molecular weight proteinuria due to a largely reduced endocytosis by proximal tubular cells (fluid-phase and receptor-mediated). The acidification of renal cortical endosomes was reduced in the KO. The failure of the PT to endocytose PTH led to an increased luminal, but not systemic concentration of this hormone. This, in turn, resulted in hyperphosphaturia due to a retrieval of the phosphate transporter NaPi-2a from the PT plasma membrane. Nephrolithiasis can be explained by altered renal handling of PTH and vitaminD, all of which are secondary to the impaired endocytosis.

There is an increased prevalence of nephrolithiasis in individuals with obesity, type II diabetes, and the metabolic syndrome. In particular, uric acid constitutes a much higher percentage of stones in these patients compared to the general stone-forming population. We strived to examine the pathophysiologic connection between the metabolic syndrome and uric acid stones.

In the vast majority of cases, the principal abnormality in uric acid stones is not hyperuricosuria but an excessively low urinary pH. Uric acid nephrolithiasis is in fact a disease of 'urinary acidification' although there is no systemic metabolic acidosis in the classical sense because acid-base balance is achieved and no excessive acid is accumulated. However, the excretion of protons using low pK closed buffers rather than the high pK open buffer ammonia dictates a low urinary pH. Since protonated uric acid has a sparingly low solubility compared to ionized urate, low urine pH promotes uric acid precipitation. Thus uric acid nephrolithiasis is an innocent bystander of low urinary pH. The link between the metabolic syndrome and urinary pH as a continuous variable is explored by epidemiologic, human metabolic, and laboratory studies. In population-based studies in stoneformers, low urinary pH is associated with higher body weight. Urinary pH is also lower with increasing number of features of the metabolic syndrome (waist circumference, high triglycerides, low high density lipoproteins, hypetension, hyperglycemia) and within each of the features, the severity of each parameter is inversely proportional to urinary pH. In metabolic studies in humans, low urinary pH is associated with low peripheral insulin sensitivity. When studied as in-patients on identical metabolic diets, patients with type II diabetes and uric acid stone-formers have high net acid generation than normal volunteers. This alone lowers urinary pH although the reason for the elevated acid load is not clear at present. In addition to high acid generation, uric acid stone formers tend to use buffers other than ammonia to buffer protons in the urinary resulting in unduly acidic urine pH. When challenged with an acute acid load, the ammonium excretion response is markedly blunted in uric acid stone-formers. A similar urinary abnormally of acidic urine pH and underutilization of ammonia is seen in the Zucker Diabetic Fatty (ZDF) rat compared to their lean counterpart. These animals have peripheral insulin resistance, elevated serum free fatty acid and have significant steatosis in their kidneys. One abnormality in the kidney is reduced expression and activity of the Na + /H + exchanger NHE3 which is the major transporter that excretes ammonium into the urine and its activity is stimulated by insulin. Causality is supported by the fact that treatment of the animals with a thiazolidinedione partially reversed the fat infiltration, urinary acidification abnormality and reduced expressed of NHE3. The direct effect of fat on the renal proximal tubule was tested in cultured cells. Provision of fatty acids beyond the oxidation capacity of the tubule leads to dose-dependent impairment of NHE3, generalized dysfunction and eventually cell death. A sub-cytotoxic dose of free fatty acid did not affect baseline NHE3 activity and expression but reduced the ability of insulin to activate NHE3. In summary, the metabolic syndrome is associated with increase acid generation that is independent of diet. This increased acid load is effectively excreted by the kidney. Failure to maximally utilize the ammonium buffer system results in lower urinary pH and titration of urate to its insoluble form as uric acid and results in uric acid nephrolithiasis. Part of the pathogenic mechanism maybe lipotoxicity from fat infiltration of organs. Uric acid nephrolithiasis is an "innocent bystander" which is a sentinel of a more generalized alteration in acid generation and excretion.

Genetic Hypercalciuria

Recurrent kidney stone production is one of the most common diseases of the bipedal human condition, occurring in up to 10% of the population in Western societies. Unlike four-footed animals who likely perish in the wild from a selection disadvantage from a painful calculus, human beings continue to function, and have the ability to express the biologic defects repetitively that result in a stone. Idiopathic hypercalciuria, where a specific gene defect has not yet been established, is a shrinking subpopulation of recurrent calcium stone formers, as specific mutations and functional polymorphisms of genes intimately or distantly related to calcium homeostasis arise from the sequencing of the human genome applied to clinical stone disease. Other postulated mechanisms can be sought for in this manner as well, and may await larger population-based studies. The familial nature of nephrolithiasis is clear and robust for most calcium-based stone formers, and may have a gender-specificity for that inheritance. The role of environment in its expression remains controversial. The systemic nature of genetic hypercalciuria may be seen through its associated effects on skeletal health and biology. Between 25-33% of children with genetic hypercalciuria have abnormally low bone density measured by dual-energy absorptiometry that cannot be explained by correction for height or body mass. Further, normalization of urinary calcium excretion with a variety of therapies is associated with improvements in bone density values over time.

A proposal for re-classifying hypercalciuria pathogenetically will be presented, and linked to observational data across the world for successful therapeutic approaches. A call for a stone registry and more careful determination of etiology will be sought through the IPNA Congress.

The systems that regulate blood pressure are plastic during development and can be permanently reset. Experiments in animals show that it is surprisingly easy to produce lifelong changes in blood pressure by minor manipulations of the mother's diet before and during pregnancy. This phenomenon has been referred to as "programming". Epidemiological and animal studies show that programmed effects operate within the normal range of growth and development, and influence the risk of hypertension, coronary heart disease and stroke in later life. A clinical study of 2003 people aged 62 years from the Helsinki birth cohort showed that two different paths of growth preceded the development of hypertension. People already diagnosed as having hypertension had small body size a birth and low weight gain from birth to two years but grew rapidly after two. At age eleven years their body size was around the average. As adults they tended to be obese and insulin resistant. A second group of people had not been diagnosed but their blood pressures were classified as hypertensive under current definitions. They were short at birth, had low weight gain from birth to two years and remained small after two. At age eleven years they were short and thin. As adults they tended to be overweight and have atherogenic lipid profiles. The first path of growth is similar to that which leads to coronary heart disease in this cohort. The second path is that which leads to stroke. This paper will present data on the maternal and placental influences through which these paths originate.

Nephron number is a key feature of the conceptual paradigm positing that cardiovascular and metabolic diseases that arise during childhood and adulthood have their origin in events that occur during fetal life. In mammals, nephrons are derived from a subset of cells resident within the metanephric blastema. Blastemal cells participate in reciprocal inductive tissue interactions with the ureteric bud. These interactions induce the ureteric bud to grow and branch. In turn, ureteric bud branches induce discrete populations of the metanephric blastema to undergo successive transitions resulting in the formation of mature nephrons. A distinct population of metanephric blastema cells in the stroma modulates branching morphogenesis and nephrogenesis. Identification of genes that control both branching morphogenesis and nephrogenesis is providing insight into the molecular pathways that could be targeted by environmental, nutritional and hormonal factors that control fetal programming. This lecture will highlight the morphologic and cellular events critical to renal branching morphogenesis and nephrogenesis, and the gene networks that regulate or counter-regulate these events. These gene networks will then be considered in the light of non-genetic factors that modulate their activities.

It is now accepted that early life environment can modulate adult phenotype, including the blood pressure. The likely primary mechanism is epigenetic modulation of gene expression during a sensitive period of fetal maturation, but the pathogenesis of the later development of hypertension is unclear. Participation by extrarenal factors such as central regulation and peripheral vascular function has been evoked; however, a strong body of experimental evidence suggests that the "setpoint" for renal regulation of Na balance and extracellular volume is altered. Because both humans and many experimental models with prenatally programmed hypertension appear to have a decrease in the total number of nephrons, impaired filtration of Na has been hypothesized to be an important pathogenetic factor. More recent evidence has suggested that postnatal inflammation and accumulation of reactive oxygen species in the renal interstitium may contribute to the genesis of hypertension by upregulating distal nephron Na transport. Furthermore, the role of renal vascular function remains to be determined. The different mechanisms are not mutually exclusive; it is conceivable that both a prenatal "priming" and a postnatal "second hit" are required for hypertension to become manifest.

J. Ingelfinger

Epidemiological studies published in the late 1980s by Barker and his group -and since replicated in many populations -provide evidence of an inverse relationship between birthweight and risk of cardiovascular disease, hypertension, and renal dysfunction in adult life. Both clinical studies and animal models have been used to investigate mechanisms underlying these observations [as cited in recent reviews. The concept that changes in the intrauterine milieu affect the growing fetus resulting in alterations in physiology and general health in later life has been termed perinatal programming or developmental origins of health and disease [DOHaD] . Yet, despite a large and burgeoning literature about this phenomenon and its relationship to cardiovascular and renal disease, involved mechanisms remain elusive. Maternal malnutrition or exposure to various medications or substances leads to an adverse in utero environment that may impair nephrogenesis, evident in experimental animal studies as well as in clinical reports in humans. Nephron deficit at birth persists throughout life, creating "low glomerular endowment, " an important risk factor for hypertension and ESRD in adulthood. For a number of years it has been hypothesized that nephron number may strongly influence blood pressure as well as susceptibility to renal disease in later life. Recently clinicopathologic observations suggest that a relationship more directly. Renal morphogenesis involves complex events in which many genes interact in the formation of the final kidney. When the normal pattern of nephrogenesis is interrupted, renal abnormalities may ensue. During renal development, two major events -ureteric bud (UB) branching and mesenchymal-to-epithelial transformation -greatly impact the outcome of renal morphogenesis. Renal malformation accounts for approximately 40 percent of childhood renal failure and represents the end result of failure of fundamental embryonic processes in UB and metanephric mesenchyme (MM) lineages. This presentation will review the data concerning renal responses to perinatal challenges as these occur and later evolve during childhood. We will consider the implications and the data available concerning screening, follow-up and management of at-risk persons.

Generation of Oxidized Lipoproteins in Obstructive Nephropathy -Atherogenic or Fibrogenic?

Children's Hospital and Regional Medical Center, Division of Pediatric Nephrology, Seattle, United States

Chronic kidney disease, regardless of etiology, is characterized by a relentless progression of fibrosis that gradually destroys the normal renal architecture, particularly in the tubulointerstitium. Obstructive uropathy accounts for approximately 35 percent of pediatric patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). After post-natal relief of obstruction, the optimal treatment of children with obstructive uropathies remains unknown and for many the progression of CKD to ESRD is inevitable. Therapeutic options are limited by an incomplete understanding of fibrogenic pathways in the kidney. The major renal fibrotic pathways identified thus far can be broadly classified into those involved in transforming growth factor beta (TGF-b) activation, macrophage-mediated inflammation, angiogenesis, and extracellular matrix production/degradation. It is becoming increasing clear that key molecules have multiple roles in several of these pathways triggering fibroinflammatory events targeting specific cell types. Oxidative stress represents an intersection of many of these fibroinflammatory pathways leading to cellular activation and tissue injury. Oxidized lipoproteins accumulate in the circulation and renal interstitium in both experimental models and patients with CKD and ESRD. Many parallels have been drawn between atherogenesis and the pathogenetic mechanisms of progressive kidney destruction by fibrosis. Although CKD is clearly associated with an increased cardiovascular risk, it is not clear whether oxidized lipoproteins amplify fibrogenic pathways in the kidney. Research in our laboratory suggests that hypercholesterolemia increases injury severity in obstructed kidneys. Scavenger receptors mediate the cellular effects of oxidized lipoproteins during atherosclerosis and activate both inflammatory and oxidative pathways. Dietary and antioxidant therapies have clear benefits in animal models but limited efficacy in patients. Our studies suggest that blocking key scavenger receptors leads to a significant attenuation of both oxidative and pro-inflammatory pathways during chronic injury by obstruction in hypercholesterolemic mice. Interventions targeting scavenger receptor signaling may represent an alternative strategy to attenuate both the progression of CKD and cardiovascular disease.

The resolution of injury and promotion of renal repair comprises a delicate balance between cell death and destruction of tissue architecture in relation to cell differentiation, maturation and extracellular matrix (ECM) remodeling. Although many studies have focused on the cellular and molecular events leading to the development of renal fibrosis, less is understood about the process of renal repair and regeneration. This is despite the fact that the kidney has a significant capacity for regeneration and cellular replacement following acute damage. The present study describes the structural, functional, and expression profile analysis of endogenous renal repair and the regenerative potential of the kidney following reversal of ureteral obstruction (R-UUO) in the mouse.10 days after unilateral ureteral obstruction there is renal tubular cell loss, activation of an inflammatory cascade leading to widespread cortical interstitial fibrosis and the loss of normal medullary architecture. Following 2 to 6 weeks after R-UUO there was marked tubular repair and regeneration of medullary components, ECM remodeling and decreased inflammatory cell infiltration. The structural repair observed at 6 weeks post-release of ureteral obstruction was associated with a 50-86% recovery of the glomerular filtration rate (GFR). Expression profile analysis was performed to visualize patterns of gene expression that were differentially expressed in the repaired and remodeling areas following R-UUO. We are also interested in the regulation of cellular recovery and the processes involved in epithelial cell re-differentiation in regenerating tubules following injury. Tubular epithelial cell cilia may play potential roles in directing the orientation of cell division and epithelial differentiation during the endogenous remodeling process. Our results suggest that renal cilium lengthening may be an important factor in the response to injury and subsequent recovery of renal function. These studies propose that a lengthening of renal epithelial cilia increases their sensitivity to flow and reduces damaging epithelial dedifferentiation in the injured renal tubules. A better understanding of the key events involved in endogenous renal repair and remodeling may open the way to new interventions based on their manipulations aimed at acceleration of renal regeneration and prevention of scarring.

Soren Nielsen has kindly agreed to present this topic, however was not able to submit an abstract.

The final regulation of urinary K excretion in the fully differentiated kidney is accomplished in the distal nephron, including the cortical collecting duct (CCD), where cell K passively diffuses into the urine through apical K selective channels. The prevalence of the SK/ROMK channel and its high P o at the resting membrane potential has led to the belief that this channel mediates baseline K secretion. Less easily detected is the BK channel which is characterized by a low P o at the physiologic resting membrane potential and [Ca 2+ ] i . BK channels are activated by membrane depolarization, elevation of [Ca 2+ ] i , and/or membrane stretch, and can be selectively blocked by iberiotoxin (IBX). We have reported that flow-stimulated net K secretion (JK) in the adult rabbit CCD is (i) blocked by IBX and (ii) associated with increases in net Na absorption (JNa) and [Ca 2+ ] i , leading us to conclude that BK channels mediate this process. Recent studies have examined the acute and chronic regulation of BK channel-mediated flow-stimulated JK. We reported that flowstimulated JK requires an increase in [Ca 2+ ] i due to luminal Ca 2+ entry and ER Ca 2+ release, microtubule integrity, and exocytic insertion of preformed channels into the apical membrane. Channel expression is regulated long term during postnatal development and by dietary K intake. Specifically, an increase in tubular fluid flow rate fails to elicit an increase in JK in the rabbit CCD until the 5 th wk of postnatal life, coincident with appearance of immunodetectable BK channels, whereas flow-induced increases in JNa and [Ca 2+ ] i in 2-wk-old CCDs are "mature". A role for the BK channel in renal K adaptation has been suggested by the observation that dietary K loading leads to an increase in abundance of BK message in microdissected CCDs with redistribution of immunodetectable channel proteins from an intracellular pool to the apical membrane. Additionally, CCDs isolated from K loaded animals demonstrate enhanced flow-stimulated JK compared to tubules from control fed animals. In sum, emerging evidence suggests that the BK channel plays a prominent role in distal K secretion in response to increases in urinary flow rate and dietary K intake. The late developmental appearance of this channel is compatible with the need of the growing animal to retain K early in postnatal life.

Recent advances in molecular genetics of hereditary hypomagnesemia substantiated the role of a variety of genes in human magnesium transport. This knowledge on underlying genetic defects helps to distinguish different clinical subtypes and gives insight into molecular components involved in magnesium transport. During the last four decades, numerous reports concerning inherited magnesium losing disorders have been published and their distinctive phenotypic features have been discussed. Phenotypic characterization of affected individuals and experimental studies of appropriate animal models have contributed to a growing knowledge of renal magnesium transport mechanisms. The identification of the affected nephron segments, the different modes of inheritance and the observation of additional characteristic symptoms promoted a classification into different subtypes of inherited magnesium losing disorders. In general, primary magnesium wasting disorders are relatively rare. The prevalence of the more frequent entities, for example Gitelman syndrome, has been estimated to be approximately 1: 50.000. For most of the other disease entities, relatively few cases have been reported in the literature. Depending on the genotype, the clinical course is sometimes mild or even asymtomatic. Therefore, the disease prevalence might be underestimated for some of these syndromes. Magnesium transport has been intensively studied in humans and various animal models leading to accepted concepts underlying the pathophysiology of the different forms of hypomagnesemia. However, the electrophysiological characterization of magnesium pathways has been complicated by unintentional simultaneous measurement of other cations so that the molecular correlates mediating mammalian magnesium transport components remained undefined. A different approach to study components of magnesium transport arises from genetic analysis of families affected with magnesium wasting diseases. Linkage studies enabled the localization of several genes involved in hereditary hypomagnesemia and in the last decade, a number of genes have been identified by positional cloning. These genes have provided first insight into mammalian magnesium transport molecules.

Distal renal tubular acidosis may be inherited as an autosomal dominant or recessive trait. Mutations in three genes -SLC4A1, ATP6V1B1 and ATP6V0A4 -are associated with the various forms of disease, and give rise to a wide spectrum of clinical severity. In general, dominant mutations do not affect ion transport function per se and do not affect hearing, whereas recessive disease is characterized by loss of function and deafness. Some unusual functional consequences of mutations in AE1 and a4 proteins are mistargeting and loss of protein-protein interaction respectively, and these will be discussed.

The Heart in Pediatric Nephrotic Syndrome Y. Frishberg Shaare Zedek Medical Center, Pediatric Nephrology, Jerusalem, Israel In recent years, the molecular bases of several conditions which lead to steroid-resistant nephrotic syndrome (SRNS) have been identified. The common denominator shared by these clinical entities is that they all result from structural defects in the glomerular barrier, thus explaining their unresponsiveness to immunosuppressants. For instance, the congenital NS of the Finnish type is caused by mutations in the NPHS1 gene encoding nephrin. A recessive form of SRNS was found to result from mutations in NPHS2 encoding podocin which is specifically expressed in podocytes. We have previously shown that a founder mutation in NPHS2 (R138X) is the prevalent cause of hereditary SRNS (55% of tested are homozygotes) among Arab children in Israel. Interestingly, we noted that a number of patients who are homozygous for the R138X mutation in podocin have a co-existing cardiac disorder. Only a few case reports described an association between SRNS and cardiac defects. We questioned whether the glomerular-barrier disorders, which have been considered to be kidney-specific, have implications on other organ-systems. Thus, we systematically reviewed the cardiac status of these SRNS patients at the time of diagnosis while they had normal blood pressure and preserved renal function (31). Cardiac anomalies were detected in 89% of children, the most common of which were cardiac hypertrophy and pulmonary stenosis. Analyzing two control groups enabled us to conclude that cardiac disorders in homozygotes for mutations in NPHS2 cannot be attributed to an association by chance or to a state of persistent NS. Because human podocin mRNA is expressed in fetal heart, we hypothesize that it may have a role in normal cardiac development and this will be an issue of further investigation. This is the first study showing a role for podocin in extra-renal tissues and therefore recommends early cardiac evaluation for timely medical management.

CVD is the world-wide biggest obstacle to long-term survival of children and adolescents with CKD. Mortality from CVD is excessively high on dialysis and continues to be a threat after renal transplantation. Early diagnosis of the individual risk for CVD would enable preventive measures on an individual basis. However, prospective studies with hard end points -cardiac events -are difficult if not impossible to conduct in children and adolescents. On the other hand, the known high morbidity and mortality in elderly dialysis patients may largely result from pre-existing comorbidity (advanced atherosclerosis has been demonstrated in this age group at initiation of dialysis). For this reason, investigations in patients with childhood onset CKD may provide a diagnostic window to study the pathogenesis of cardiac and vascular changes in subjects without comorbidities. Several studies using non-invasive measurements of surrogate markers for CVD have demonstrated a pattern of early systemic CVD, including changes in intima-media thickness (IMT) of conduit arteries (aorta, a. carotis) and muscular arteries (a. femoralis), altered function of peripheral resistance arteries (venous occlusion plethysmography) and abnormalities in the heart (echocardiography). Patients show a significant decrease in post-ischemic vascular reactivity with evidence of vascular stiffness and frequently have extraosseous calcifications often involving coronary arteries and heart valves. Importantly, these studies have found little evidence for correlations with classical risk factors (except hypertension), but with abnormalities of calcium and phosphorus metabolism and their therapy, including the intake of active vitamin D preparations and calcium-containing phosphate binders. Thus, patients with childhood-onset CKD are at high risk to develop systemic cardiovascular changes, which may represent a new disease originating from the survival of CKD, a previously deadly disease, and interventions for the prevention of renal osteodystrophy. This therapeutic challenge needs to be addressed with high priority to enable long-term survival of children with CKD.

While their mere existence is still questioned by some investigators, lipid rafts have recently gained a large amount of attention because of their apparent involvement in various cellular processes, including signaling, membrane trafficking, polarization, and endo-as well as exocytosis of proteins as well as pathogens. Membrane rafts have been defined as small (10-200 nm) heterogeneous, highly dynamic, sterol-and sphingolipid-enriched domains that compartmentalize cellular processes and that can sometimes be stabilized into larger platforms by protein-protein or proteinlipid interactions. Rafts are of special interest for pediatric nephrologists for two reasons: 1. They play a critical role in immune cell activation, especially in the formation of the immunological synapse (IS), and thus in many important disease processes affecting our patients, including -but not limited to -transplant rejection. Beyond their participation in IS formation, rafts also facilitate signaling through other immune cell receptors, such as the interleukin-2 receptors, where they may ascertain cytokine selectivity and specificity. 2. Equally important, rafts serve as essential site for proper interactions between nephrin and podocin, thus establishing the integrity of the glomerular filter. General aspects of raft biology as well as their role in immune cell signaling will be reviewed in more depth in this presentation. Raft involvement in glomerular filter formation and especially genetic aspects relevant to disturbances of this involvement and of the associated integrity of the filter, as seen in hereditary nephrotic syndromes, are discussed in subsequent presentations in this symposium.

Reports of familial forms of FSGS date back to 1956, with the observation of an autosomal recessive disease primarily within the Finnish population. It is characterized by massive proteinuria in utero, with up to 20 to 30 grams of protein loss per day. NPHS1 encodes a gene product termed nephrin that localizes to lipid rafts within the slit diaphragm of the podocyte. Steroid-resistant nephrotic syndrome (SRNS) is an autosomal recessive nephrotic syndrome and manifests between 3 months and 5 years of age, rapid progression to ESRD, and with few cases of recurrence after renal transplantation. The gene product is podocin (NPHS2), located on 1q25-31. Podocin most likely functions in the structural organization of the slit diaphragm and regulation of its filtration function. It has been shown to interact in vivo with both nephrin and CD2-associated protein (CD2AP), a cytoplasmic binding partner of nephrin. Mutations in the alpha-actinin 4 gene (ACTN4), localized to chromosome 19q13 have been associated with autosomal dominant FSGS, characterized by adult onset disease of variable severity and rate of progression to ESRD. Fractions of the mutant protein have been shown to form large aggregates within podocytes ultimately compromising the function of the normal actin cytoskeleton, both through its abnormal function and toxic accumulation. Recently, a disease-causing mutation for hereditary FSGS has been localized to chromosome 11q 21-22, and identified as the transient receptor potential cation channel, subfamily C, member 6 (TRPC6). The missense mutation causes a highly conserved proline in the first ankyrin repeat of TRPC6 to become a glutamine at position 112 (P112Q). The TRPC6 P112Q mutation causes increased and prolonged calcium transients in transfected cells. The mutant channel also significantly enhances cation signals triggered by AT1 receptor activation. Biotinylation and immunostaining studies reveal that the mutation also appears to cause mislocalization of the ion channel to the cell surface. Whereas previously reported mutations such as NPHS1, NPHS2 and ACTN4 have emphasized the importance of cytoskeletal and structural proteins in glomerular diseases, TRPC6 related FSGS suggests an additional mechanism for renal disease pathogenesis. Knowledge of TRPC6 mediated calcium entry into cells may offer unique insights into therapeutic options for glomerular diseases.

T. Huber University Hospital, Department of Nephrology, Freiburg, Germany

The sense of touch relies on the ability of specialized sensory cells to convert mechanical stimulation into ionic currents. Mechanoreceptor cells respond to external force by opening ion channels. Recent findings highlight now a potential role for the mechanosensitive ion channel TRPC6 at the glomerular filtration barrier. TRPC6 localizes to the slit diaphragm and mutations of TRPC6 cause familial glomerular disease. Mutations of the PHB-domain protein Podocin are the most common cause of hereditary nephrotic syndrome and we demonstrate that Podocin and MEC-2, the closest homologue of Podocin in Caenorhabditis elegans, bind cholesterol to regulate the activity of associated ion channel complexes: DEG/ENaC channels for MEC-2 and TRPC channels for Podocin. Both the MEC-2-dependent activation of mechanosensation in C. elegans and the Podocin-mediated activation of TRPC6 channels requires cholesterol. Our data suggest that the recruitment of cholesterol by Podocin and MEC-2 to ion channels plays an important role in regulating their activity. These findings promote the concept that Podocin, similar to the function of MEC-2, may be part of a mechanosensitive protein complex at the slit diaphragm of podocytes.

Isidro Salusky has kindly agreed to present this topic, however was not able to submit an abstract

Is there a Role for Bisphosphonates in Pediatric Bone Disease? F. Santos Hospital Universitario Central de Asturias, Universidad de Oviedo, Pediatria, Oviedo, Spain Bisphosphonates are being increasingly and successfully utilized to prevent bone fractures and treat bone pain in children with severe osteoporosis from different origins. A largest experience has been accumulated with the administration of cycles of intravenous pamidronate in children with osteogenesis imperfecta. In addition, to the bone resorption inhibition mediated by their effects on osteoclasts, bisphosphonates given in large doses inhibit normal and ectopic mineralization. Thus, bisphosphonates have also been used in children with hypercalcemia and in the treatment of calcinosis and heterotopic ossification, Bisphosphonates have been administered to renal transplanted adults to prevent or treat bone loss induced by chronic administration of glucocorticoids and might also be useful in the management of urolithiasis in selected hypercalciuric patients. The potential clinical utilization of bisphosphonates in the prevention and treatment of vascular calcification in patients with chronic renal failure is now being explored, although no data on children in this clinical setting are available. A number of questions as to the precise clinical indications to start bisphosphonates' administration, the type of bisphosphonate to be used, the duration of the treatment, the best way to monitor its effectiveness and the risk of longterm toxic effects remain to be answered.

Water is the solvent in which all metabolic reactions occur. Body water moves between compartments with diverse compositions that are separated by semi-permeable lipid membranes. Water exchanges also occur between maternal and fetal blood separated by several layers of tissue, the so-called placental membranes. The fetus appears to be dependent on placental flow and perfusion pressure for the bulk of his water requirements, and the prostanoids play a significant role in the control of ureteroplacental and umbilicoplacental blood flows. Osmotic and hydrostatic forces control placental water flux. The amniotic fluid (AF) appears early during gestation and its volume increases rapidly. The net AF volume turnover approximates 95% per day. Major sources of AF production are represented by fetal lungs secretions, and by fetal urine. The AF is initially isotonic, and becomes hypotonic when significant amounts of dilute urine are produced by the fetus. Disposal of water is effected by fetal swallowing of AF and by the intramembranous (IM) pathway, that is the route of absorption between the fetal circulation and the amniotic cavity. This route appears to play an important role in the overall regulation of AF volume and composition. The fact that water crosses the IM pathway in excess of solutes suggests a role for aquaporin water channels in allowing this transport. Circumstantial evidence indicates that the IM water flow is regulated by aquaporin 1. Homeostatic changes in placental permeability could thus be up or down-regulated by the number of aquaporin water channels in the membrane.

Systemic lupus (SLE) is a multigenic and multifactorial disease, characterized by B lymphocytes polyclonal activation with decreased tolerance, autoantibodies production and immune complexes formation. DNA was initially thought to be the mayor auto-antigen, however, it is not immunogen and injection of DNA-anti DNA does not induce lupus nephritis. The complex of DNA and histones (nulceosome) is provided with a positive electrical charge which favours the binding to heparansulphates in the GBM. In SLE high levels of nucleosomes are present in circulation due to accelerated lymphocytes apoptosis or defective removal of apoptotic cells. Lupus nephritis (LN) is consequent to deposition of immune complexes, activation of lymphomononuclear cells and reactivity of renal cells. The WHO classification of lupus nephritis has been recently reviewed by the ISN/RPS. The new classification takes into account a distinction between forms without endocapillary hypercellularity (mesangial or subepithelial deposits) and others with endocapillary hypercellularity (involving less or more than 50% with segmental or global distribution). Prognosis and treatment of LN need a flexible therapy, tailored on histological picture and clinical data. Steroids must be given at high doses for induction therapy but have drawbacks of heavy morbidity and mortality. The addition of immunosuppressive drugs improves the therapeutic index. The NIH protocol used Cyclophosphamide (CYC) pulses in severe LN (monthly pulse for 6 months followed by quarterly pulses for 1 year). More recent studies, comparing low with high doses CYC pulses, failed to prove a significantly different effect. For maintenance therapy of LN, mycofenolate mofetil may be a good alternative to CYA or AZA. Rituximab, a chymeric monoclonal antibody anti CD20, which selectively and profoundly depletes B lymphocytes, has provided very interesting results in SLE with poor response to classical therapy or in relapse. The possibility of rotating agents with different side effects may allow to lower the doses of steroids, to reduce drug-specific morbidity, and to improve the compliance of patients. Efforts should be done to minimize steroids and CYC which are very effective but are the main responsible of invalidating and even lifethreatening complications.

For half a century now, physicians have tried to classify vasculitic syndromes. Classification of vasculitides is required to put in perspective the pathogenesis and therapeutic advances and to provide a uniform language, given the variation in the epidemiology of these diseases. The "American College of Rheumatology" criteria have been used for classification and the Chapel Hill Consensus criteria for definition purposes in children as well however they are based totally on adult criteria. Taking into account the differences in children and the new developments in medicine a group of pediatricians have aimed to revise the classification of vasculitic syndromes encountered in children. The consensus group consisted of a multinational panel of experts who were pediatricians, pediatric rheumatologists and pediatric nephrologists. The Delphi and nominal group techniques were used. This project has provided classification criteria for Henoch-Schönlein Purpura, childhood polyarteritis nodosa, Wegener Granulomatosis and Takayasu Arteritis. This was an important task since appropriate classification criteria for vasculitis in children has been missing for far too long. We hope that the international and multispecialist composition of the expert group involved will facilitate the applicability of this classification for most vasculitic diseases in children seen around the world and will meet the needs of pediatricians. These criteria are now to be validated using a large registry for childhood vasculitides.

Anti-neutrophil cytoplasm antibodies (ANCA) are well established as a diagnostic marker for small vessel vasculitis, including Wegener's granulomatosis and microscopic polyangiitis. There is increasing evidence that ANCA are directly involved in the pathogenesis of vascular inflammation in these disorders. In clinical studies, there is a clear relationship between levels of ANCA and the activity and extent of disease, and ANCA positivity confers an increased risk of relapse. Rising titres of ANCA predict relapse, and two studies have shown that pre-emptive treatment of those with rising titres can prevent relapse. Of great interest is the recent report of a newborn child who developed glomerulonephritis and lung haemorrhage after transplacental transfer of ANCA. In vitro experiments have shown that ANCA can activate cytokine primed neutrophils to release oxygen radicals, enzymes and inflammatory cytokines. This is achieved through both direct F(ab) 2 binding and Fc receptor engagement. In co-culture, ANCA can induce neutrophil mediated killing of endothelial cells. In flow chamber studies, ANCA can induce neutrophil adhesion and transmigration across endothelial cell monolayers. More recently, ANCA have been shown to be pathogenic in experimental models of disease. High titre anti-MPO antibodies induced by immunisation of MPO deficient mice can transfer glomerulonephritis and vasculitis to naive recipients. Immunisation of rats with MPO induces anti-MPO autoantibodies which lead to crescentic glomerulonephritis. Intravital microscopy in this model confirms that ANCA can induce leukocyte transmigration and microvascular haemorrhage in vivo. However, many questions remain unanswered. Some patients may have high levels of ANCA without disease activity, and others may have typical disease without detectable ANCA. It seems likely that T cells may be involved, not only in providing help for ANCA synthesis, but also in mediating tissue damage. It is also possible that an additional inflammatory stimulus, for example an infection is required, to enhance the inflammatory effects of ANCA. Greater understanding of the role of ANCA in vascular inflammation will hopefully lead to safer and more effective approaches to treatment.

Hacettepe University, Faculty of Medicine, Department of Pediatric Nephrology, Ankara, Turkey

The therapy of vasculitic syndromes poses a problem for the caring pediatrician. The treatment of ANCA associated vasculitides will be presented to cover Microscopic Polyangiitis, Wegener granulomatosis and Churg Strauss syndrome. Treatment of all ANCA-associated diseases are similar. Steroids and cyclophosphamide are the mainstay of induction treatment. In severe patients with kidney involvement steroids can be given in the form of intravenous methylprednisolone for 1-3 days (15-30 mg/kg/d, max.1 gr), followed by daily oral corticosteroids (1.5 mg/kg/d, max.60 mg/d). Cyclophosphamide may be given at 2mg/kg/d p. o. or monthly IV pulses 0.75gr/sqm for at least 6 months. For maintenance treatment there are again many different regimens for oral corticosteroids. Along with corticosteroids for maintenance regimen there are a number of protocols suggesting the continuation of cyclophosphamide. The CYCAZAREM study has shown that the replacement of cyclophosphamide with azathioprine at 3 months was also as effective for disease control. Methotrexate has also been shown to be an alternative for maintenance treatment. Treatment of the childhood polyarteritis nodosa (PAN) with systemic disease is similar to that of ANCA-related vasculitides. There are a number of non-ANCA associated vasculitides in childhood. The most frequent in childhood are Henoch-Schönlein purpura (HSP), Kawasaki disease (KD) and Takayasu Arteritis (TA). The treatment of HSP is usually symptomatic. However, for severe kidney involvement with extracapillary proliferation and rapidly progressive disease severe immunosuppressive treatment is indicated. Triple treatment with steroids, cyclophoshamide and dipyridamole have been given in various series. For KD intravenous immunoglobulin at a dose of 2g/kg still remains the first choice of treatment along with salicylates. For TA therapy depends on the extent of vessel invovlement: severe disease necessitates steroids and cyclophosphamide whereas for less intensive vessel involvement methotrexate and steroids may suffice. Treatment period depends on the actiivty of the disease.

LB. Zimmerhackl

Haemolytic uraemic syndrome (HUS) is the most common cause of acute renal failure in children. The syndrome is defined by the triad of microangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure (creatinine over the 97 th percentile). World wide HUS is increasing. In a German/Austrian multicenter study we follow 628 children with HUS occurring in the years 1997 to 2002.5 year follow-up data are now available www. hus-online. at. From this study the following results are obvious. HUS affects predominantly children of kindergarten age. The median age at onset is 2,9 years. The majority of HUS is of infectious origin. Shigatoxin (Stx) producing Escherichia coli (STEC, EHEC) are present in over 80% of patients. The predominant shigatoxin type is type II. HUS is classified into two clinical subgroups. "Typical" HUS usually occurs after a prodrome of diarrhoea (D+HUS), and "atypical" HUS (aHUS), which is not associated with diarrhoea (D-HUS). The majority of D+HUS worldwide is caused by EHEC type O157: H7, which is transmitted to humans via different routes. However non-O157 groups are emerging and are predominant in Europe. Transmission of disease in elder patients is predominantly through food poisoning and direct contact to farm animals. In infants and small children direct transmission from human to human seems to be more likely. Currently there are no specific therapies preventing the disease course. Anti-shigatoxin antibodies are being tested by several companies. If this may prevent HUS is open to study. Otherwise the therapy at present is symptomatic. Parenteral volume expansion before HUS in patients with positive Stx or EHEC stool culture may counteract the effect of thrombotic process before development of HUS and attenuate renal injury. Use of antibiotics, antimotility agents, narcotics and non-steroidal anti-inflammatory drugs should be avoided during the acute phase in particular during the prodromal phase. From our own study the prevention is best done by preventing primary EHEC infection. However, patients with severe course and long term sequelae should be screened for genetic abnormalities in the complement system. If auto antibodies against complement proteins or the vWF play an relevant role is under discussion. Patients under one year of age at onset have a significant worse outcome and should be kept under surveillance. Patients below 3 month of age are very likely to have an inborn error of complement or vWF and should be tested specifically. The European registry on HUS and related disorders may help to determine these abnormalities: www. haemolytic-uraemic-syndrome. org. In order to improve long term outcome of these patients, increased awareness and an European (International?) task force is mandatory.

In adults with chronic kidney disease, protein-energy malnutrition and inflammation are risk factors for death and accelerated cardiovascular disease. The "Malnutrition-Inflammation-Cachexia Syndrome" (MICS); anorexia, increased basal metabolic rate, and loss of lean body mass is associated with low serum albumin, decreased protein intake, elevated C-Reactive Protein, and low serum cholesterol levels in adults. In children, MICS manifests as growth retardation. Clinical research focusing on the evolution of MICS in pediatric CKD to understand its causes and consequences and how nutritional interventions alter its course may be the key to improving survival in CKD. Baseline cross sectional data from the ongoing Chronic Kidney Disease in Children study, of children (n=335) aged 1-16yrs (mean=11.1yrs) with estimated GFR 30±90 ml/min/1.73 m 2 (mean iohexol GFR 38 ml/min/1.73 m 2 ) shows substantial growth retardation in CKD with median height percentile=23. Greater height deficits are seen at lower GFR's. Symptoms of decreased appetite and nausea are reported by 35% and 47% of those with GFR <30 respectively. Mean LDL cholesterol is lowest in those with GFR <30 (97 vs 123mg/dl in GFR 30±40 ml/min/1.73 m 2 group). Serum albumin declines as serum creatinine increases (r=-0.22). Unlike previous reports in adult CKD, increases in CRP were not associated with lower GFR at baseline. Further exploration of the MICS in pediatric CKD will be presented.

The causes of growth failure in pediatric patients with chronic kidney disease (CKD) are multifactorial.

It is an open question as to which factors play a key role in diminishing physical growth. It is also unclear which mechanisms may become pace makers for the therapeutic improvement of growth. Furthermore, growth failure in children with CKD affects total body height, body proportions and composition as well as organ development. Growth failure may also lead to disproportion which can only be identified by detailed anthropometric measurements. We were able to demonstrate that CKD patients have a specific age-dependent pattern of growth and distinct changes in segmental growth (trunk, arm and leg length) from birth to adolescence. Leg growth in relation to other parameters of linear growth showed the most dynamic growth changes and emerged as the best indicator of growth in children with CKD. Trunk growth had little synchronicity with leg growth. Furthermore, we found that anthropometric measurements can be used as a diagnostic tool in distinguishing different sub-groups of CKD patients, for instance, children with syndromic CKD. In the heterogeneous group of patients with focal and segmental glomerulosclerosis, patients with Schimke's disease were found to have a dramatically decreased sitting height/leg length ratio. As the disturbance in growth of CKD patients is a marker of the severity of the disease and of the quality of renal care, the annual analysis of growth failure from early childhood to adolescence should be used as a landmark information of the quality of medical care and as a helpful tool in differential diagnosis and of specific courses of CKD in sub-groups of patients. For example, patients with congenital or acquired renal diseases, dialyzed or transplanted patients and in gender differences. In addition, anthropometric measurements are able to identify specific growth patterns in children with CKD, which should be considered in the assessment of treatment efficacy such as in rhGH therapy.

B. Tönshoff, L. Weber, B. Höcker University Children's Hospital, 1st Department of Pediatrics, Heidelberg, Germany

It is currently under debate whether steroid avoidance or late steroid withdrawal provides the best overall risk-to-benefit ratio in pediatric renal transplantation. Late steroid withdrawal has the advantage over steroid avoidance that immunological high-risk patients and those with unstable graft function can easily be identified beforehand and be excluded from steroid-free immunosuppression. In order to further validate this approach, we performed a prospective randomized open-label multicenter trial in 41 low-risk pediatric renal transplant recipients (12 f, 29 m; mean age 10.1 yrs; range, 3.4 to 17.8) on CsA (target trough level 100-200 ng/ml), MMF (1200 mg/m 2 per day) and methylprednisolone (3) (4) mg/m 2 per day), who were randomly assigned >1 year posttransplant to continue steroids or to withdraw over a period of 3 months. An interim analysis was performed at a mean observation period of 29 mo after study entry; 31 patients had been followed for at least 15 mo. There were 3 drop-outs (1 reversible acute rejection episode, 1 switch to sirolimus and 1 to tacrolimus). Transplant function as assessed by calculated CCR remained stable in both groups, no graft was lost. Prepubertal children off steroids gained relative height from baseline -1.5±0.5 SDS to -0.9±0.6 SDS after 2 yrs, while patients on steroids lost relative height (-1.1±0 .6 SDS at baseline, -1.6±0.7 SDS after 2 yrs); a comparable pattern was observed in pubertal patients. The standardized body mass in patients off steroids declined from 0.75±1.01 SDS at baseline to 0.31±1.17 after 2 yrs (P<0.05), while it tended to increase in patients on steroids (baseline, 0.40±1.35 SDS; after 2 yrs, 0.56±1.39). The rate of adverse events, mainly infections, was comparable in both groups. Patients off steroids required less frequently antihypertensive medication (62%) than patients on steroids (93%). A significant reduction of serum cholesterol (by 20%) and triglycerides (by 13%) in response to steroid withdrawal was observed. Conclusions: This interim analysis indicates that late steroid withdrawal in selected pediatric renal transplant recipients on CsA and MMF is safe, allows catch-up growth and ameliorates cardiovascular risk factors. At the IPNA meeting, full 12 month outcome data of all patients will be available.

U. Frei, J. Noeldeke

Renal transplantation faces two major challenges: the organ shortage resulting in extended waiting times and an aging population resulting in increased death with a functioning graft. The Eurotransplant Senior Program (ESP) allocates kidneys within a narrow geographic area from donors aged >65 years to recipients >65 years regardless of HLA. This analysis investigates the impact of the ESP on waiting time, graft and patient survival. The ESP group (n=1406, old to old) was compared to two groups allocated via the Eurotransplant Kidney Allocation System (ETKAS) with either similar donor age [old to any (O/A), donor age >65, n=446] or recipient age [any to old, (A/O), recipient age 60-64, n=1687]. All patients were transplanted between 1999 and 2004. Since initiation of the ESP (1999), availability of elderly donors doubled and waiting time for ESP patients decreased. Local allocation led to shorter cold ischemia time (11.9 vs. >17.0 hours, p<0.001) and less delayed graft function (DGF, ESP 29.7% vs O/A 36.2%, p=0.047) but 5-10% higher acute rejection rates. Importantly, graft and patient survival were not negatively affected by the ESP allocation scheme. The ESP age matching of elderly donors and recipients is an effective allocation system for organs from elderly donors.

The Effect of Age Matching on the Duration of the Waiting Time A. Rahmel, M. Slot, J. Smits Eurotransplant International, Leiden, the Netherlands In Eurotransplant the proportion of children, i. e. patients aged under the age of 16 at time of registration, with end-stage renal disease (ESRD) on the renal waiting list amounts to only 1.2%. Despite this small proportion the Eurotransplant Kidney Allocation System (ETKAS) specially addresses pediatric transplant candidates. In order to increase their chances of receiving a transplant in time children are assigned via ETKAS extra points for HLA matching and receive an age bonus. In order to evaluate this allocation policy, the chances for receiving a kidney for patients in different age groups were evaluated. For the cohort of patients registered in the year 1999, a 5 year followup was obtained. For patients aged under 6 at time of registration [N=134] 47% and 81% received a kidney from a post-mortem donor, within 1 year and 5 years after listing. For children aged 6 to 10 [N=108] these rates were at 1 and 5 years after listing 31% and 67%, and for children between age 11 and 16 [N=192] 33% and 72% respectively. Adult patients were less likely to receive an organ: 11% and 42% of patients aged between 16 and 64 were transplanted within 1 and 5 years after listing. Senior ESRD patients can benefit from the Eurotransplant Senior Program (ESP), their chances for a transplant were 28% and 61% within 1 and 5 years, respectively. The life span of a renal allograft is limited in time. In the Eurotransplant experience 80% of the post-mortem kidneys used for transplantation in children failed within 20 years, compared to 70% for the living donor renal transplants (RTX). Donor age is an important factor associated with long term renal allograft function. Age matching between donor and recipient is hampered by the low number of pediatric donors. In the period 2000-2005, 78 heart beating kidney donors aged under 1 were reported and used for RTX, 69 donors were between 2 and 5 years of age, and 319 donors were between 6 and 16 years old. In the same period 9981 adult donors were reported and used for transplantation. In the period 2000-2005, 18% of the pediatric donor kidneys ultimately served a pediatric recipient.

To improve the allocation of pediatric donors to pediatric recipients, ET is in the process of implementing a rule giving pediatric recipients priority in case of pediatric donors.

Gender and sex hormones are playing a central role in the incidence and progression of different renal diseases. Vascular tone, endothelial function and immune response are influenced by gender.

In renal transplantation ischemic injury is always present. Females are more resistant to postischemic renal failure than males. Following ischemia/reperfusion injury renal vascular resistance decreases, allowing fast restitution of blood flow and oxygen supply in females. Additionally, stabilization and preservation of tubular function following ischemia is achieved by the protection of Na+/K+ ATP-ase and heat shock protein activity contributing to the observed gender differences. Posttransplant immune reactions also differ between genders. Female gender predisposes to more severe acute rejection following kidney transplantation, partly due to differences in the effectivity of immunosuppressants used. Ineffective immunosuppression in females, as well as different cytotoxicity profile of the drugs is contributing to more prone immune reactions shortly after transplantation resulting in more severe acute rejection. In contrast, similar to the slower deterioration of other renal diseases, progression of chronic graft failure is less pronounced in females in experimental and clinical settings. Estradiol decreases profibrotic processes, preserves endothelial function and modifies influx of immune cells into the graft. The fine balance between alloantigen dependent immune reactions and alloantigen independent factors and its impact on longterm graft function is modified by gender. New evidences supporting the significance of sexual dimorphism following kidney transplantation may present the base of gender modified therapeutic approaches in the future.

IgA Nephropathy: Aetiology, Incidence, and Geographic Distribution

IgA nephropathy (IgAN) is characterized by mesangial deposits of IgA, proliferation of mesangial cells and expansion of matrix. The accumulation of IgA and complement fractions within glomeruli was initially ascribed to deposition of IgA immune complexes (IgAIC) due to mucosal immune response with predominant IgA synthesis. This hypothesis has offered an explanation of the relationship between infections of the upper airways and gross hematuria. High levels of IgAIC have been detected in 30-70% of patients, mostly of polymeric IgA1, and polymeric IgA1 are detectable in renal deposits. This observation is consistent with hypothesis of either bone marrow or mucosal origin. However, no specific viral or alimentary antigens have been found in mesangial deposits, and the qualitative properties of polymeric IgA1 have rather become of interest, particularly the glycosylation pattern of IgA1. Human IgA1 is O-glycosylated with carbohydrate chains of N-acetyl galactosamine (GalNAc) and galactose (Gal) which may be covered with sialic acid (Neu5Ac). Patients with IgAN exhibit circulating IgA1 with reduced Gal and/or Neu5Ac and increased exposure of N-GalNAc. Such aberrantly glycosylated IgA can circulate in monomeric form or participate in the formation of autoaggregates/true immune complexes. It likely escapes clearance by hepatic receptors and has a preferential renal deposition by virtue of enhanced reactivity with the mesangial matrix components. The role of a triggering event has not ruled out. In recent reports, antigens of bacterial origin and the secretory tract component have been found in renal deposits, making scientists reconsidering again the role of bacterial infections. Tonsils recurrent infections may provide a suitable aetiology for IgAN, and the effect of tonsillectomy on the long term outcome of IgAN is under evaluation. The prevalence of IgAN varies in different areas, due to ethnic and environmental factors, being particularly frequent in Mediterranean Europe, Northern Europe, Asia and Australia. It is still debated whether differencies in frequency, clinical features and disease progression among patients with IgAN from different Countries are actually due to uneven distribution of this diseases or these discrepancies are due to the different criteria for performing renal biopsy.

Definition. IgAN is characterized by the presence of dominant (or codominant) mesangial deposits of IgA on immunofluorescence microscopy, frequently with C3 and sometimes with IgG or IgM. Classification. The glomeruli display a broad spectrum of histologic changes, related in part to the differences in the indication for the biopsy of the referring nephrologist. A number of classification systems have been used to describe the histologic manifestations of IgAN. Two will be referred to here:

The system of M. Haas (AJKD 29:829-842, 1997 ): 1) Minimal histologic lesion -The glomeruli exhibit no more than a minimal increase in mesangial cellularity, without segmental sclerosis or crescents.

2) FSGS-like -The glomeruli display focal segmental sclerosis in a pattern resembling primary focal segmental glomerulosclerosis, with at most a minimal increase in mesangial cellularity and no crescents.

3) Focal proliferative glomerulonephritis (GN) -50% or fewer of the glomeruli are hypercellular. The increase in cellularity may be limited to mesangial areas, or there may be obstruction of glomerular capillaries by proliferated endocapillary cells. Crescents may be present. 4) Diffuse proliferative GN -More than 50% of glomeruli are hypercellular. The hypercellularity may be segmental or global, and crescents may be present. 5) Advanced chronic GN -40% or more of the glomeruli are globally sclerotic, and/or there is 40% or more tubular atrophy or loss in the cortex.

The system of S. Emancipator (Heptinstall's Pathology of the Kidney, Lippincott-Raven, Philadelphia, 1998, pp 479-512) :

A -Normal/minimal glomerular lesions B -Focal mesangial proliferation C -Diffuse mesangial proliferation D1 -Focal segmental endocapillary proliferation superimposed on mesangial proliferation D2 -Focal segmental endocapillary proliferation alone E -Diffuse endocapillary proliferation F -Diffuse extracapillary proliferation (crescents in >70%), with or without endocapillary proliferation G -Glomerulosclerosis (>70% of the glomeruli are sclerotic) H -Unclassifiable or combined lesions Diffuse proliferative GN (C) and focal proliferative GN (D1) are the major patterns of expression of glomerular injury. Indicators of a poor outcome. These include a high proportion of glomeruli with crescents, numerous sclerotic glomeruli, interstitial fibrosis and tubular atrophy, extension of the IgA deposits into the peripheral glomerular capillary walls, and hyaline arteriolosclerosis. Differential diagnosis. Mesangial IgA deposits are present in Henoch-Schönlein nephropathy, and may be present in lupus nephritis, chronic liver disease, coeliac sprue, certain dermatologic diseases, and some rheumatologic diseases.

IgA nephropathy [IgAN] is defined by the presence of mesangial IgA, but otherwise the histopathological and clinical features are very variable. We do not yet know sufficient about pathogenic mechanisms to understand whether IgAN is a single disease. Although traditionally called an 'immune complex' disease there is no direct evidence that mesangial IgA deposition in IgAN occurs through classical antigen-antibody interactions. Mesangial cells do carry receptors for IgA, which may play a key role in IgA deposition and subsequent injury, but these are not yet fully characterised. Mesangial IgA in IgAN is polymeric IgA1. There is no evidence of mucosal immune system overactivity, indeed there seems to be underproduction and abnormal T cell control of mucosal IgA production, along with overproduction by the marrow of IgA1 IgA1 has a hinge region peptide structure which is a site for O-glycosylation. In IgAN circulating and mesangial IgA1 both have abnormal O-glycosylation at the hinge region. The same defect is seen in Henoch-Schönlein purpura only when there is renal involvement. The glycosylation defect is not due to abnormal peptide structure of the hinge; the possibility that there is reduced activity of the key enzyme b1, 3 galactosyltransferase in B cells or plasma cells has not yet been confirmed. Alternatively the glycosylation changes may reflect a shift in the production of mucosal type of IgA1 to the marrow. While IgA1 deposition is caused by disease mechanisms specific to IgAN, subsequent inflammatory and fibrotic events are probably driven by mechanisms common to other chronic glomerular disease. In some patients IgA1 deposition is not followed by inflammation, in others inflammation resolves without fibrosis. Cytokine and growth factor production by mesangial cells is a sufficient explanation for glomerular inflammation and fibrosis. However little is yet understood of any genetic or environmental influences which protect some patients from progressive renal injury.

Our recent controlled trials by The Japanese Pediatric IgA Nephropathy Treatment Study Group demonstrated that treatment of children with severe IgA nephropathy with prednisolone, azathioprine, heparin/warfarin, and dipyridamole for 2 years early in the course of the diseaseprevents immunological renal injury and progression of the disease. The majority of patients with IgA nephropathy in our series are diagnosed early in the course of the disease, and the asymptomatic period before the discovery of urinary abnormalities is short. Early diagnosis and early treatment is very important in IgA nephropathy. 1. Combined therapy for severe childhood IgA nephropathy (J Am Soc Nephrol 10: [101] [102] [103] [104] [105] [106] [107] [108] [109] 1999) . Seventy-eight children with newly diagnosed IgA nephropathy showing diffuse mesangial proliferation were randomly assigned to receive either the combined therapy of prednisolone, azathioprine, heparin-warfarin, and dipyridamole for two years (group 1) or the combination of heparin-warfarin and dipyridamole for two years (group 2). Urinary protein excretion was significantly reduced in group 1 patients, but remained unchanged in group 2 patients. The percentage of glomeruli showing sclerosis was unchanged in group 1 patients, but significantly increased in group 2 patients. 2. Steroid treatment for severe childhood IgA nephropathy (Clin J Am Soc Nephrol, 1:511-517, 2006) . In this study we have compared the effects of prednisolone, azathioprine, warfarin, and dipyridamole (combination) with those of prednisolone alone in 80 children with newly diagnosed IgA nephropathy showing diffuse mesangial proliferation. Patients were randomly assigned to receive either the combination or prednisolone alone for two years. The primary endpoint was the disappearance of proteinuria, defined as urinary protein excretion <0.1 g/m 2 /day. Thirty-nine of the 40 patients receiving the combination and 39 of the 40 receiving prednisolone completed the trial. Thirty-six of the 39 patients (92.3%) receiving the combination and 29 of the 39 (74.4%) receiving prednisolone reached the primary endpoint by the two-year follow-up point (p=0.007 log-rank). The percentage of sclerosed glomeruli was unchanged in the patients receiving the combination, but increased in the prednisolone group (p=0.0003). The frequency of side-effects was similar in the two groups.

Long-term administration of recombinant human erythropoietin (EPO) has become the most common way of treating anemia in chronic renal disease. Standard amounts per unit body weight have been recommended for the initial dose. However, several authors have noted that the dose per unit body weight needed for a given response is higher in younger children than in older children or adolescents and that it is increasing with decreasing body weight. Furthermore, for a given absolute dose of EPO the outcome was investigated in adult hemodialysis patients, but no dependence was found in 54 patients weighing 45-86 kg. A similar model to the hemoglobin-time data of 8 children aged 8-15 years treated with EPO for renal anemia did not find an impact of body weight on response when it was modelled in terms of absolute dose. In a similar analysis to the hemoglobin-time data 52 children and adolescents aged 5-20 years were analyzed, in order to more definitively answer the question if, for given absolute doses the hematopoetic response to EPO in children depends on body weight. Neither the dose response parameter E max and ED 50 showed dependence on body weight. The median hemoglobin response to a standard dose was similar to that reported for adults. It can be concluded that younger and smaller children need relatively more EPO than older children. Doses for children should be specified as absolute amounts rather than amounts per unit body weight. References: Scigalla P. Effect of recombinant human erythropoietin treatment on renal anemia and body growth of children with end-stage renal disease. In: Baldamus CA, Scigalla P, Wieczorek L, et al, editors Erythropoetic agents are the mainstay of treatment for renal anemia. Although there are several different marketed forms of erythropoetin, they are not substantially different in their ability to stimulate erythropoesis. However, Darbepoetin, which differs in one amino acid, and has additional glycosylation sites, has a longer half-life and therefore a presumed longer duration of action. This provides a theoretical advantage, suggesting that less frequent injections will be required. Clinical experience and studies have confirmed that both erythropoetin (EPO) and Darbepoetin (DAR) are effective to maintain Hb values within the recommended range. Also, though there is some experience with EPO injected every couple of weeks, the overall evidence suggests that DAR has a longer duration of action, and injections are required less frequently. For many children, particularly the pre-dialysis population, anemia is successfully controlled with DAR injected every 3-4 weeks. However, this apparent advantage of DAR is somewhat reduced because of the increased pain reported with DAR injections compared to EPO. Both EPO and DAR have been used successfully in children of all ages. With EPO, the doses required to maintain Hb values appear to be increased in infants compared to older children; this may not be the case with DAR, but there is much less experience with use of DAR in infants. Also, the administration of DAR in infants is hindered by the need to inject portion of a unidose pre-filled syringe, which may introduce inaccuracies in dosing, is wasteful, and is not user-friendly. The side effect profile for each product is similar, and specifically each has been associated with development of hypertension, which is most likely with higher Hb values. Pure red cell aplasia has also been reported with each product. Thrombocytosis has been reported with DAR use.

Overall, there is little to recommend one product over the other. The need for less frequent injections may favor DAR for use in most children beyond infancy, whereas it is easier to administer EPO accurately in infants.

How much Iron is Needed and how much is Toxic?

Iron deficiency is the primary reason for ineffective erythropoiesis in patients with chronic kidney disease (CKD) who receive an erythropoiesis stimulating agent (ESA). Reasons for iron deficiency include inadequate dietary intake, blood loss from the gastrointestinal tract, frequent blood tests, loss of blood in the extracorporeal circuit of hemodialysis (HD), as well as the hepcidin related impairment of the intestinal absorption of iron and its release from the reticuloendothelial system. Supplementation of iron can be by either the oral or intravenous (IV) routes, although the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (K/DOQI) strongly recommends the preferential use of IV iron in children and adult patients receiving HD. The K/DOQI recommended target iron indices for all children on dialysis are a serum ferritin >100ng/ml and a transferrin saturation (TSAT) >20%. While the serum ferritin should not regularly be >500 ng/ml, some such patients will achieve a higher hemoglobin value following an IV course of iron therapy. Of the IV iron agents, the non-dextran products appear to be safest, and pediatric dosing recommendations exist for ferric gluconate and are currently being studied for iron sucrose. Differences do exist for the clinical (e. g. proteinuria) and subclinical (e. g. oxidative injury) toxicities associated with the currently available IV iron products and should be taken into consideration when prescribed.

Until recently the major physiological function of erythropoietin (EPO) was thought to be the induction of erythropoiesis. However, a growing body of evidence indicates that EPO has tissueprotective properties and prevents ischemia induced tissue damage in several organs including the kidney. A main target of EPO´s action is the endothelium, and one of the pivotal intracellular pathways mediating the beneficial effects of EPO is the activation of Akt, i. e. serine/threonine protein kinase B. As a result, Akt phosphorylates the proapoptotic factor Bad, which in turn causes inhibition of programmed cell death (apoptosis). Moreover, experimental studies revelead that EPO is a potent regulator of endotheial progenitor cell (EPC) proliferation and differentiation. Collectively, these data support the hypothesis that EPO is a key molecule in the process of endothelial (vascular) repair and neoangiogenesis. Treatment with rHuEPO or analogues could therefore open new therapeutic strategies in regenerative cardiovascular medicine.

Introduction: Africa as a continent is besieged by many health challenges including Malaria, HIV (upwards of 60% of paediatric admissions), Tuberculosis and Malnutrition with an Infant Mortality Rate (IMR) ranging from 62(Southern Africa) to 132(Mozambique). Good health facilities are on the whole not available except in the extreme north and south of the continent with Doctors/100 000 population in South Africa 69 but in Kenya only 13 and even lower in other parts of Africa. Renal Disease: Renal disease in adults is an unknown quantity with no information being available regarding children's renal disease, where many babies do not even have access to antenatal ultrasounds. Situation in South Africa: In reality, there are only 2 centres (Cape Town and Johannesburg/ Pretoria) doing paediatric dialysis and transplantation in significant numbers with small numbers interspersed in the rest of the country. This raises numerous issues: -Accessibility for children to renal care -Retaining minimum standards of care for children -both dialysis and transplantation -combined with adult units -Central Government funding in form of tertiary services grant for paediatric renal care -Children not first priority on any transplant program in terms of organ allocation -Private facilities vs State facilities -Ethical decisions Dialysis facilities: Peritoneal dialysis (PD) first line therapy for acute renal failure, as can be performed in any setting with minimal equipment and expertise. In the setting at RXH, we have a greater than 60% survival in infants and children dialysed using PD even in a sophisticated intensive care setting. Haemodialysis and Chronic Dialysis may not be easily available in most settings and realistically need transfer to one of the major centres. Transplantation: Again limited to only few centres, with at least 30% living related donations from family members. Initial good 1 year (90%) and 5 year (80%) graft survival but results then deteriorating as patients enter their adolescent years often with little support and transfer to adult units in their early teens. Controversial issues here include access to one kidney transplant only, no chronic dialysis if not suitable for transplant and transplantation in HIV positive recipients. Conclusions: Adequate resource allocation is required for paediatric renal care especially where resources are limited.

Immunosuppression remains the cornerstone of successful transplantation. In developing countries transplantation is mostly from living donors and transplant is thus a once in a lifetime chance. In this backdrop immunosuppression is a challenge as several issues have to be overcome. Namely, non-availability of newer drugs, high costs and paucity of drug monitoring facilities. In most countries immunosuppression is based on a triple drug regimen of Cyclosporin (CyA), Prednisolone (Pred) and Azathioprine (Aza). In the last few years MMF and Tacrolimus (Tac) has been initiated in a few centres. Several tailoring strategies have been employed taking into consideration costs, drug availability, tissue typing facilities and drug monitoring. Firstly in HLA identical transplants which constitute 15-20% of the total, CyA based regimen are used. Marked reduction to 1-2 mg/kg at 6 months and complete withdrawal at one year in rejection free transplants is safe with continuing of Aza and Pred. Secondly several centres selectively use Tac and MMF in cases with early rejection or transplants with >3 mismatches. It is possible to switch to CyA or Aza after 6 months on individual basis. Thirdly induction protocol with ATG for 3 days in transplants with >4 mismatches and in retransplants is cost effective. Cost considerations have increased the use of generic calcinurin inhibitors with market share of 20-100% in different countries. Co administration of P450 competitors has reduced doses of CyA by 50-60% with considerable cost reductions. SIUT has been running a living related transplant program for more than 20 years with dialysis and follow-up of recipients and donors. Keeping in mind economic constraints a model of government public partnership was developed which provides all facilities including drugs free of cost. We adopted a number of tailoring strategies e. g. strict monitoring, tailoring by HLA match and donor age and use of biological agents in risk groups. In first 10 years we used parent drugs, however increasing costs necessitated use of generics after establishing bioequivalence in controlled trials. Graft survival rates were maintained at 92% and 85% at 1 and 5 years.

In conclusion, immunosuppression in developing countries require besides newer drugs, monitoring facilities, affordable costs and regular follow-up as transplantation for majority is once in a lifetime chance and failure equates with death.

Occurrence of infections following kidney transplantation is a major reason for hospitalization, and an important cause for renal dysfunction & mortality in developing countries. More than 50% renal transplant recipients get serious infections, with a 20-40% risk of mortality. Infections in the first month after transplantation are similar to those in surgical patients; opportunistic pathogens and CMV predominate between 1-6 months; and tuberculosis (TB) after 6 months. The risk of TB in patients on maintenance dialysis & following transplantation is between 10-20%. The onset of TB is usually within 12 months of transplantation. Clinical syndromes include pleuropulmonary TB, followed by disseminated TB, pyrexia of unknown origin and lymph node disease. Demonstration of M. tuberculosis, on microscopy or culture might not be possible. Nonrifampicin based treatment regimens (INH, pyrazinamide, ethambutol, fluoroquinolone for 3 months, followed by HEF for 9 months) are used. INH prophylaxis (6-9 months) is advised in patients with tuberculin positivity or contact with active tuberculosis. CMV disease results in considerable morbidity & mortality; its timing is influenced by donor/recipient serological combination, state prior to transplantation, use of antilymphocyte induction therapy or preventive strategies. CMV disease is characterized by a non-specific febrile illness; features of enterocolitis, pneumonia, hepatitis, myocarditis, esophagitis, chorioretinitis & bone marrow involvement are variable; disseminated disease is rare. CMV disease exacerbates the net immunosuppression, increasing the risk for opportunistic infections. Patients with CMV disease are also at risk for acute rejection and chronic allograft injury, atherosclerosis & vascular injury. Diagnosis of CMV disease is based on a combination of viral serology, shell vial cultures, pp65 antigen assay and PCR. The cost of prophylaxis and treatment is a major limitation to the use of ganciclovir or valganciclovir. Other infections in transplant recipients include malaria, P. carinii and fungi (cryptococcosis, candidiasis, mucormycosis, aspergillosis). Infections are an important cause of morbidity & mortality in renal transplant recipients. Their management continues to be challenging due to difficulties in diagnosis, unsatisfactory follow-up and cost of medications.

Ethical Issues of Renal Replacement Therapies N. Orta, P. Zibaoui, E. Lara University of Carabobo/Insalud, Pediatric Nephrology, Valencia, Venezuela Important ethical issues in pediatric nephrology (PN): genetic and molecular techniques, prenatal therapies for urinary anomalies, treatment of children with chronic renal disease (ESRD). Ecosonography can detect nephrourological anomalies and studies of amniotic fluid give information on chromosome alterations and renal function. Particular situations, can lead to dilemmas related to pregnancy interruption and neonatal dialysis and transplantation (DT) possibilities. Renal insufficiency (RI) presents at any age, and peritoneal, hemodialysis or hemofiltration could be applied. Patients without structural abnormalities, RI secondary to toxics or isquemic nephropathies have better prognosis. These procedures are complicated and costly and increases, and may have secondary effects with ethical implications. Treatment by dialysis developed in the 60's and inclusion of children was not considered. This has changed with advances in DT. Since 1970's DT programs were setup for children, but received criticisms and considered unethical, but were continued because of familiar and humanitarian demands and today it is clear that children benefit with that. Scientific societies recommend: 1. Children who receive dialysis must meet the following criteria: -Diagnosis of ESRD, legal authorization, possibility of transplantation, acceptable quality of life; may not be rejected for economic, social or psychological reasons, nor gender, age, race or mental conditions. Biopsies are the current 'gold standard' for monitoring transplant patients, but it has been shown that even mild rejection episodes, based on pathology grading, can have poor outcomes and even biopsies with normal early pathology can progress rapidly with chronic allograft injury. There is considerable inter-observer variability of biopsy pathology readings that adds an additional confounder to this method of analysis. Identification of non-invasive biomarkers in blood or other fluids would allow for the possible elimination of frequent biopsies. Hence, the identification of diagnostic and predictive non-invasive genomic markers will be a worthy tool to aid in the clinical monitoring of transplant patients. The use of DNA microarrays as a hypothesis generation tool for determining gene expression differences across thousands of genes in a data set is increasing. Recently, the use of microarrays has been applied to the transplant field and holds great promise for unraveling the mechanisms at play in various transplant processes and for identifying new tissue specific and non-invasive biomarkers predictive of clinical outcomes. As microarrays produce large amounts of data, bioinformatics tools are being developed to determine gene expression patterns. Gene clustering and class prediction tools aid in the discovery of molecular signatures in different disease processes while literature mining, gene family analysis and pathway analysis help in understanding the biological relevance of these signatures. Initial studies in acute rejection and graft dysfunction have produced possible markers for risk stratification of the rejection event and have suggested underlying mechanisms at play, that may now allow us to test novel drugs for treating specific acute rejection episodes. The most exciting application of microarrays lies in our ability to predict clinical outcomes by non-invasive serial monitoring, eliminate the requirement of transplant biopsies and individualize patient management by accurately predicting the patient's sensitivity to immunosuppression-sufficient to suppress the allo-response, yet insufficient to abrogate the innate response. Responsible array data handling and accessible reporting will open new doors for transplant researchers through increased use of computers and collaborations towards these kinds of novel insights and treatment options for transplant patients in the future. This talk focuses on DNA microarrays, their application to transplantation, and discusses some of their limitations and recent applications, as well as some key research studies where DNA microarrays are applied to understanding the molecular differences in acute transplant rejection that segregate and likely control the differences in rejection treatment responsiveness as well as decline in graft function, as well as gaining insights into the different biological processes that govern these differences.

The molecular pathogenesis of VUR is not well understood. Uroplakins (UPs) are expressed in the urothelium and are developmentally regulated by Rab27b and TBX genes. UP II and IIIa-null mice exhibit a primary (1 o ) VUR phenotype. Using microarrays and RT-PCR, we analyzed gene expression in surgically-discarded ureteric tissue from children undergoing reimplantation for 1 o reflux, compared with adult living-related transplant donors as normal controls, as well as children with 2 o reflux (megaureter, duplicated ureters, and posterior urethral valves) as age-matched disease controls. We also studied urine protein profiles using 2-dimensional electrophoresis (2D-PAGE) followed by time-of-flight mass spectroscopy (Q-TOF-MS). RT-PCR showed partial expression of ureteric UPIa, UPIb, UPII and UPIIIa genes in patients with 1 o reflux. Protein screening using western immunobloting confirmed that some uroplakins were undetectable. Real-time RT-PCR revealed that ureteric UP Ia, UP Ib, UPII, and UP IIIa gene expression decreased significantly, whereas UPIIIb gene expression increased at least 2-fold compared to controls. Compared with patients with 2 o VUR, the decrease of UPIIIa expression in those with 1 o reflux was highly statistically significant (P<0.00001). The expression of Rab27b and TBX genes also decreased significantly in patients with 1 o and 2 o reflux as well. Total urinary protein concentration increased by 6-fold in the 1 o VUR patients without detectable renal scarring on DMSA scans; and increased further in patients with renal scarring, 13-fold for 1 o VUR and 11-fold for 2 o VUR patients. Proteomic analyses of proteinuria revealed an overall increase of protein with MW>60.4 kDa in the PI range 4.0 to 7.0 in patients. Q-TOF MS identified one predominant urinary protein of ~ 105 kDa as sera-transferrin, which was confirmed by ELISA quantitation. We hypothesize that the abnormal developmental expression pattern of the UP, Rab27b and TBX genes in VUR patients results in abnormal urothelial functions, which lead to leakage and/or secretion of proteins into the urine, and that this occurs in the absence of scarring from urinary infections. Further identification of these protein biomarkers may lead to non-invasive diagnostic tests for VUR.

Biomarker Discovery in Acute Kidney Injury P. Devarajan Cincinnati Children's Hospital Medical Center, Department of Pediatric Nephrology and Hypertension, Cincinnati, United States Acute kidney injury (AKI), previously referred to as acute renal failure (ARF), represents a common and persistent problem in clinical medicine. Despite significant improvements in therapeutics, the mortality and morbidity associated with AKI remain high. A major reason for this is the lack of early markers for AKI, akin to troponins in acute myocardial disease, and hence an unacceptable delay in initiating therapy. Fortunately, the application of innovative technologies such as functional genomics and proteomics to human and animal models of AKI has recently uncovered several novel genes and gene products that are emerging as biomarkers. The most promising of these are chronicled in this symposium. These include a plasma panel (NGAL and cystatin C) and a urine panel (NGAL, . Since they represent sequentially expressed biomarkers, it is likely that the AKI panels will be useful for timing the initial insult and assessing the duration of AKI. Based on the differential expression of the biomarkers, it is also likely that the AKI panels will distinguish between the various types and etiologies of AKI. However, they have hitherto been tested only in small studies and in a limited number of clinical situations. It will be important in future studies to validate the sensitivity and specificity of these biomarker panels in clinical samples from large cohorts and from multiple clinical situations. Such studies will be markedly facilitated by the availability of commercial tools for the reliable and reproducible measurement of biomarkers across different laboratories. A. Watson Children and Young People's Kidney Unit, Notthingham University Hospitals, Nottingham, United Kingdom The achievement of adequate chronic peritoneal dialysis in children requires close attention to clinical, dietetic and psychosocial aspects of care. Successful dialysis is dependent upon excellent peritoneal access and swan neck coil catheters with downward facing exit sites are increasingly favoured with many placed laparoscopically. Automated peritoneal dialysis is employed in most developed countries but adolescents may be given the choice of CAPD which may be the only modality available in developing countries. Training and support by committed nursing staff are of paramount importance as is regular review by a paediatric renal dietitian. Growth parameters should be regularly monitored and supplemental enteral feeding introduced early. Many infants are nasogastrically fed, but the preferred route for supplemental enteral feeding is via a gastrostomy which can be placed at the same time as the PD catheter. Dialysis fill volumes should be assessed in terms of body surface area and intra-abdominal pressure measurements. There can be discrepancies between urea and creatinine clearances and adequate dialysis includes combining clinical parameters with regular growth measurements as well as biochemical data including phosphate, calcium and parathyroid levels. Peritoneal function tests are useful in monitoring progress but the greatest challenges are in sustaining long-term dialysis, particularly in infants where transplantation is likely to be delayed. Support for the families with a respite care 'package' may delay or prevent burnout and possibly reduce peritonitis rates.

Conventonal PD solutions are acidic, contain unphysiological concentrations of lactate and glucose and highly toxic glucose degradation products (GDP), which are substrates for advanced glycation end product (AGE) formation. Repeated administration induces epithelial to mesenchymal cell transition, loss of the mesothel cell layer, progressive submesothelial fibrosis and angiogenesis, ultimately leading to ultrafiltration failure. Meanwhile PD solutions with an improved toxicity profile are available. Multi chamber PD solutions separate glucose from the buffer at a very low pH, which largely prevents GDP formation. After mixture pH is close to normal. They are equally effective with regard to solute-and water transport, reduce inflow pain and systemic AGE load. Dialysate effluent markers indicate increased mesothelial cell mass, reduced peritoneal inflammation and reduced angiogenesis. Animal studies demonstrate preservation of PD membrane morphology and function, respective human biopsy data however are pending. A European paediatric multi centre trial accomplished recently elucidates the impact of the lactate and bicarbonate buffer. A randomized cross over trial in adult patients points to an improved preservation of residual renal function; a Korean registry suggests improved technique and patient survival. Icodextrin solutions reduce glucose and GDP exposure, improve extracellular fluid status, left ventricular mass and stabilize membrane function in anuric adult CAPD patients and should be beneficial in children, too. Amino acid based solutions achieve similar clearance and ultrafiltration rates, reduce glucose and GDP load and allow for a phosphate free amino acid supply. The nutritional benefit however is questionable. Other, thus far experimental strategies include addition of locally active compounds to PD fluids such as GDP scavengers, inhibitors of AGE formation and antifibrotic agents. Surface active phospholipids may increase peritoneal contact area and ultrafiltration. Gene therapy appears highly promising but is still far from being clinically applied. In summary, there is substantial evidence for increased biocompatibility of the recently introduced multi chamber and icodextrin based PD solutions. They should improved long term morbidity and mortality of PD patients; this however still needs to be proven.

The Impact of the IPPR on the Treatment of Peritonitis B. A. Warady Children's Mercy Hospital and Clinics, Pediatrics Nephrology, Kansas City, United States The International Pediatric Peritonitis Registry (IPPR) is an initiative that was established to evaluate the safety and efficacy of largely opinion based peritonitis treatment guidelines in which empiric antibiotic therapy (1 st generation cephalosporin and ceftazidime or a glycopeptide and ceftazidime) was stratified by disease severity. Forty-seven centers from 14 countries contributed data on 392 children and 501 peritonitis episodes treated in accordance with the guidelines. Culturenegative peritonitis accounted for 31% of all episodes, with a marked regional variability in the incidence of this disorder, as well as in the peritonitis causative organisms. Overall, 89% of cases achieved full functional recovery, a portion following relapsing peritonitis (9%). In-vitro evaluation revealed only 69% sensitivity of gram-positive organisms to a 1 st generation cephalosporin (Eastern Europe > North America) and 80% sensitivity of gram-negative organisms to ceftazidime. In contrast, 94% of gram-positive organisms and 93% of gram-negative organisms were sensitive to the combination of either a 1 st generation cephalosporin or an aminoglycoside. Whereas the risk of empiric treatment failure was associated with the presence of a gram-negative infection (p=0.0004), neither the risk factors assumed by the guidelines nor the choice of empiric therapy were predictive of the final functional outcome of the peritonitis episodes. The data collected by the IPPR will serve as an important source of evidence to be incorporated into revised pediatric peritonitis treatment guidelines.

Ch. Aufricht Medical University, Pediatrics, Vienna, Austria Peritoneal dialysis (PD) is a safe, cost effective and widely used form of renal replacement therapy in patients with end stage renal failure. However, up to a third of patients on PD will suffer from technical failure during their course. Identification of the patients at highest risk would be of high clinical relevance. Cytotoxicity of PD fluids due to low pH, hyperosmolarity, and/or high concentrations of lactate, glucose and its degradation products causes mesothelial cell injury that ranges from minor cellular dysfunction to overt (apo)necrosis. The same physicochemical properties of PDF that cause such cellular injury also induce pathways leading to repair and recovery. This so-called cellular stress response results in a switch of the cellular machinery from routine procedures towards reaction against stressors. The complex machinery of the cellular stress responses not only counteract direct toxic injury caused by PDF but also attenuate inflammation or other potentially deleterious cellular processes. Infectious, uremic and toxic injuries might converge in cellular inflammation. Whereas inflammatory processes triggered by infection protect the peritoneal cavity against invading microorganism, chronic sterile smoldering 'cytotoxic' inflammation may result in aberrant healing processes and peritoneal fibrosis. Recently, polymorphisms of many proteins involved in relevant cellular responses have been described and related to altered resistance and/or susceptibility to pathogenetic processes with potential influence in PD. In this review, we will focus on key effectors of stress responses, of cellular inflammation and of fibrogenesis such as heat shock proteins (HSP), cytokines (Il-6), chemokines (Il-8) toll-like receptors (TLR) and growth factors. Given the recently shown role of these 'players' for the interplay between mesothelial injury, inflammation and cytoprotection, these polymorphisms will likely be relevant for mesothelial cell damage during PD. Taken together, the ability to understand -and ultimately modify -the risk profile of a given patient will be essential for tailoring individual PD therapies.

The pathologic diagnosis of chronic allograft nephropathy (CAN) was introduced in 1993 by the Banff classification system for renal allograft injury. It originally included at least four entities that it was acknowledged could not always be distinguished by biopsy: 1) chronic rejection; 2) chronic calcineurin inhibitor (CNI) toxicity; 3) hypertensive vascular disease; 4) chronic infection and/or reflux (Solez, KI 1993 44: 411) . Over the ensuing decade, the definition of CAN has expanded and fluctuated such that some pathologists have come to use the term to mean a specific pathologic entity comprising "…progressive graft dysfunction accompanied by chronic interstitial fibrosis, tubular atrophy, vascular occlusive changes and glomerulosclerosis. " (Nankivell, NEJM 2003 349: 2326 , while others have suggested CAN should be used to describe all causes of renal allograft dysfunction involving fibrosis. The resulting confusion over terminology has in some ways hindered the growing awareness of the multiple discrete, diagnosable and often treatable diseases capable of causing chronic graft injury. These diseases include: 1) chronic (primarily antibody-mediated) rejection; 2) de novo and recurrent glomerular disease; 3) calcineurin inhibitor toxicity; 4) interstitial fibrosis and tubular atrophy without evidence of any specific etiology. To this list should be added other recognizable causes of late graft dysfunction such as polyoma virus infection and hypertension. In the new Banff 2005 classification CAN will no longer be a diagnostic category (Colvin, World Transplant Congress, 2006) . Instead, the term sclerosis will be used to describe: "interstitial fibrosis/tubular atrophy, not otherwise specified, " or "IF/TA NOS. " The increasing use of protocol biopsies in clinically stable patients has dramatically increased awareness of the ongoing pathological changes almost every renal allograft appears to be undergoing almost from the first moments of engraftment. Techniques are now available in most centers to reliably recognize the presence of chronic antibody-mediated rejection. These include: 1) typical morphological findings: lamination of glomerular basement membranes, arterial intimal fibrosis, interstitial fibrosis/tubular atrophy; 2) C4d staining in peritubular capillaries or glomeruli; 3) the presence of circulating donorspecific antibodies (Takemoto AJT 2004 4: 1033 . Treatment of late, chronic antibody-mediated rejection is in its infancy and may include use of anti-B cell antibody (rituximab), IVIg, and/or plasmapheresis. Calcineurin inhibitor toxicity can be more reliably identified by focusing on blood vessels in the allograft, primarily the location of hyaline deposits in the arterioles. Nodular, peripheral hyalinosis is found almost exclusively in CNI toxicity, whereas sub-endothelial and transmural hyaline deposits are non-specific and can be seen in hypertension, aging and diabetic nephropathy. There is increasing concern that recent gains in short-term renal allograft survival and reductions in acute rejection rates have not resulted in improved long-term graft survival. While this is likely due to multiple factors, including infections and malignancies associated with over immunosuppression, unrecognized (sub-clinical) acute cellular rejection (Moreso AJT 2006 6: 747), and noncompliance in some patients, much evidence points to the primary role of CNI toxicity in many if not the majority of chronically failing allografts maintained on CNI's. Experience with conversion from CNI to sirolimus in adult patients has been reviewed in a recent editorial (Betard Nephrol Dial Transplant 2006 21: Editorial Comments) . In 10 studies involving nearly 400 patients, between 54% and 80% of patients with late allograft dysfunction failed to respond favorably to CNI withdrawal and replacement with sirolimus. Acute rejection episodes were rare, occurring in only six patients. Common adverse effects included dyslipidemia, anemia and proteinuria. In one study, 32 of 50 patients developed proteinuria after conversion, 18 in the nephrotic range. Pediatric experience with CNI withdrawal has been limited (Kerecuk, Pediatr Nephrol 2005 20: 1630 Falger, Pediatr Transplant 2006 10: 565, Hocker, Pediatr Transplant 2006 . Our recent experience at Stanford with CNI withdrawal in 17 patients was not favorable, with 41% of patients experiencing an associated acute rejection episode (Weintraub, WTC 2006) . Prior history of acute rejection significantly increased the relative risk of acute rejection after CNI withdrawal (RR=1.8), and proteinuria was common. Patients with advanced chronic graft dysfunction were at increased risk for graft loss. In summary, the use of the term CAN to describe all causes of chronically failing renal allografts is to be discouraged in favor of a search for specific etiologies whenever possible. Antibody-mediated rejection and CNI toxicity are major causes of late allograft dysfunction. Protocol biopsies are helpful in identifying patients with treatable causes of late allograft dysfunction. CNI withdrawal/avoidance may be successful, but optimum patient selection criteria and withdrawal/replacement strategies have not been determined. Pediatric experience to date with CNI withdrawal has been limited, but it appears that late withdrawal after CNI injury and graft dysfunction have become well established may be associated with inferior outcomes. Prospective trials in pediatric patients are needed to address these issues.

Which Immunosuppression in Pediatric Transplantation? P. Hoyer University Children's Hospital, Essen, Germany Recent results in pediatric renal transplantation have reached one year graft survival rates better than 90%. Current immunosuppressive drugs should be classified according to their interference with the immunesynapsis as signal 1, signal 2 and signal 3 blocking agents. The variety of immunosuppressive drugs does allow more treatment combinations than the potential number of large scale studies in children. The definition of current unmet needs should guide employment of drugs. Calcineurin inhibitors (CNI) are still the basis of immunosuppression. Individual risk profile leads to preferences for cyclosporine or tacrolimus. While in adults CNI reduction seems to be the major goal, the search for steroid sparing or avoidance protocols has attracted major interest in pediatric transplantation. Growth and body configuration as well as cardiovascular risk factors should be in the focus of research. Antibody induction protocols, mainly with IL-2 receptor antibodies, are increasingly popular, but efficacy is less clear than concluded from adult studies and might depend on initial combination therapy. MMF (Cellcept®) or MPA (Myfortic®) are effective drugs with CNI sparing potential. Early adequate dosing seems to be of greater importance than the choice of the CNI, but the price to pay may be an increase in infectious complications. mTOR inhibitors are promising in avoiding nephrotoxic side-effects; specific side effects on male gonadal function and possible interference with growth should be considered before any recommendation can be given. FTY 720 would have been of especial interest for children because of maintaining viral infectious response, but phase-2 studies are on withhold. The vision of tolerance has stimulated research on regulatory t-cells; i. e. CD4 CD25+t-reg cells and the mastergene FOXP3. The impact of lymphocyte depletion induction protocols with campath on operational tolerance needs further studies. Newer drugs in development are ISA 242, a cyclosporine analog without nephrotoxicity; a modified release form of tacrolimus which might improve compliance; the phosphokinase inhibitor AEB071 with the potential to avoid CNIs; the JAK3 inhibitor Cyp 690, 550 which might interfere with signal 3 (IL2 and IL15-receptor); and LEA29Y (belatacept) with blocks costimulatory signals. According to the new European drug legislation some of these drugs will be subject for mandatory testing in pediatric patients to get marketing authorisation. The future might be a more tailored immunosuppression according to the induvidual needs of the patient.

Immunosuppression minimization strategies, under the umbrella of a newer generation of more powerful induction and maintenance immunosuppressants, are being increasingly applied to pediatric organ transplantation, with the greatest emphasis on minimization of steroids and calcineurin inhibitor agents. Safe elimination of these steroids carry unprecedented advantages for reducing patient morbidity and chronic graft injury, but may also result in unanticipated changes in immunological homeostasis and drug pharmacokinetics, heralding closer surveillance for posttransplant infections and alterations in drug bioavailability and dosing, as well as break-through immunologic responses. In single center studies, pediatric renal transplantation appears safe without steroids. Daclizumab first dose doubling and extended use for 6 months replaces steroids effectively without evidence of over-immunosuppression, and may be the pivotal causative for the reduced acute rejection seen in the face of steroid avoidance. This pilot protocol has been tested in a prospective, multicenter randomized US and Canadian study. B. Maecker, C. Klein Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany Posttransplant lymphoproliferative disorders are severe complications of immunosuppressive therapy after solid organ transplantation causing significant morbidity and mortality. To define prognostic factors, we have analyzed 55 pediatric solid organ graft recipients (kidney, liver, heart/lung) that were reported to the German Ped-PTLD registry. PTLD was diagnosed at a median time of 29 months post organ transplantation with sigifcantly shorter lagtime in liver versus heart or renal graft recipients. The five-year overall and event-free survival was 68% and 59%, respectively. Stage IV disease with bone marrow and/or CNS involvement was independently associated with poor survival. No differences in outcome were observed between early and late onset PTLD, monomorphic or polymorphic PTLD, and EBV-positive or EBV-negative PTLD, respectively. Patients with Burkitt-like PTLD and c-myc translocations had very short survival. These factors should be important to consider for future prospective interdisciplinary trials that are urgently needed to define rational treatment strategies.

Cystinosis is an autosomal recessive lysosomal storage disorder affecting children and adults all over the world. In cystinosis cystine is trapped in the lysosomal compartment due to a defect in its egress transport protein cystinosin encoded by the gene CTNS. By mechanisms still not fully understood this leads to tubular and glomerular kidney and other organ failures (e. g., thyroid, muscles) if left untreated. Kidney involvement is prominent from shortly after birth on as renal tubular Fanconi syndrome with the clinical consequences of failure to thrive and rickets. Cystinosis is the single most common cause of renal Fanconi syndrome in childhood. Therefore, any recognition of renal glucosuria, generalized aminoaciduria, phosphaturia, small molecular weight proteinuria, polyuria, and metabolic acidosis (due to renal bicarbonate loss) should lead to prompt consideration of cystinosis as possible cause. This can be done utilizing biochemical analytical methods measuring the cystine content of polymorphonuclear leucocytes. Corneal cystine crystals, seen in slit lamp examination, are pathognomic as well, but may not be visible before 16 months of age. Left undiagnosed and untreated, patients will develop in addition to the existing tubular insufficiencies pronounced glomerular kidney failure often already present at diagnosis and inevitably leading to end stage renal failure typically at the end of the first decade of life. Kidney failure in cystinosis presents differently from other forms of glomerular kidney failure because of the overlap of tubular and glomerular insufficiencies. Kidney transplantation will be curative with respect to kidney function. Specific treatment with cysteamine to lower the intralysosomal cystine content apparently is as important as before transplantation to prevent or attenuate other organ failures and therefore has to be continued after kidney transplantation. Cysteamine treatment has been introduced in the 1970s and has been approved in the 1990s. Early diagnosis and diligent treatment is able to prevent or ameliorate major organ complications. Unfortunately, until now no newborn screening exists due to the biochemistry and cell biology involved. The high prevalence of a European founder mutation, i. e., a 57 kb deletion in the CTNS gene, makes molecular based methods not feasible.

Lowe Syndrome and Dent's Disease: Two Ends of a Spectrum D. Böckenhauer Great Ormond Street Hospital for Children NHS Trust, Nephrology, London, United Kingdom Lowe syndrome and Dent's disease are X-linked disorders; the former is a systemic disorder characterized by cataracts, mental retardation and proximal tubulopathy whilst the latter was originally described as an isolated kidney disorder with tubular proteinuria, hypercalciuria/ nephrocalcinosis and progressive renal impairment. Mutations in OCRL1 underlie Lowe syndrome, whereas the majority of cases with Dent's disease are caused by mutations in CLCN5. Recently, mutations in OCRL1 have been identified in a subgroup of patients with Dent's Disease (also called Dent-2). It is unclear, why some patients with OCRL1 mutations get Dent's Disease, while others develop Lowe syndrome. However, careful clinical observation has revealed that Dent-2 patients have evidence of systemic involvement. Moreover, the degree of severity of symptoms in Lowe syndrome is highly variable. Thus, mutations in OCRL1 can cause a spectrum of symptoms, from tubular proteinuria and hypercalciuria to the full manifestations of Lowe syndrome. Here, we will review the clinical phenotype of the disorders, what is known about their pathophysiology and discuss genotype/phenotype correlation. Fabry disease, the second most prevalent lysosomal storage disorder after Gaucher disease, is an Xlinked inborn error of the glycosphingolipid metabolic pathway and affects approximately 1:44,000 live births. Mutations in the gene encoding alpha-galactosidase A, lysosomal hydrolase, lead to systemic glycosphingolipid deposition, resulting in profound dysfunction of neurological, renal, cardiac, and cerebrovascular systems. The initial phase begins in childhood or adolescence and is characterized by neuropathic pain, angiokeratomas, and ocular deposits. The later phase is distinguished by progressive cardiac, cerebral, and renal involvement, leading to multi-organ dysfunction and death. Few patients have historically survived past their mid 50s. Although renal involvement usually becomes prominent in adulthood, adolescents may develop proteinuria and decreased glomerular filtration rate. Timely diagnosis is critical, given that the enzyme replacement therapy likely delays progression of the serious complications of Fabry disease and may have potentially preventive benefits. Specifically, there is growing evidence that initiation of enzyme therapy slows progression of chronic kidney disease (CKD); it remains unknown whether enzyme therapy in the currently employed doses can prevent CKD. Pediatricians have a particularly important role in making the diagnosis, since they are likely to be the first providers to encounter Fabry patients and thus initiate therapy before irreversible tissue injury develops. Nephrologists should consider the diagnosis of Fabry disease when a patients present with CKD with nephrotic or subnephrotic proteinuria, often with skin lesions (but these may be limited in distribution), episodic extremity pain, and/or psychiatric problems. Further research is required to determine the efficacy of enzyme replacement therapy to prevent organ damage in children, to identify optimal therapeutic doses and schedules, and to define efficacy of additional treatments for Fabry kidney disease, include angiotensin converting enzyme inhibitors and angiotensin receptor blockers.

W. Van't Hoff Great Ormond Street Hospital for Children NHS Trust, Pediatric Nephrology, London, United Kingdom Children with a complete deficiency of methylmalonyl CoA mutase develop both renal tubular and glomerular dysfunction. The renal tubular dysfunction is characterised by renal tubular acidosis, defective urinary concentration and hyporeninaemic hypoaldosteronism. A chronic interstitial nephritis also develops leading to long-term glomerular renal damage. Chronic kidney disaes is not evident on routine testing as muscle mass is reduced and protein intake is markedly restricted. Formal measurement of GFR using Chromium 51 EDTA showed that 7 of 12 such MMA patients have a GFR <60 mls/min/1.73 m 2 ), and by 12 years, 7 of 9 patients had a GFR <40. Most MMA patients with CKD do not have excess proteinuria nor hypertension. Although Vit B12 responsive MMA patients in general have a more favourable outcome, late onset renal complications have been seen. In addition to CKD, MMA patients can develop cardiomyopathy, pancreatitis, gut dysmotility and chronic or acute encephalopathy. Management is based on a protein-restricted, high calorie diet, allopurinol to control hyperuricaemia, supplements of carnitine and metronidazole therapy to reduce production of propionate. Haemodialysis has successfully cleared plasma MMA and improved the metabolic and nutritional status. Liver transplantation has been performed in a number of younger children, as enzyme replacement therapy, but is associated with a significant morbidity and mortality (including late neurological deaths). Renal transplantation has been reported in a small number of older patients but it is not yet clear how good the graft outcome will be. Combined liver-kidney transplantation has been undertaken again in small numbers, with a high morbidity and significant mortality although there are a very few remarkable survivors. So far, there are only centre specific experiences and unfortunately reviewing the literature will not give a full picture of long-term outcome and complications, due to the bias of the reported results towards favourable outcomes. There is a clear need to share data on the management of these rare patients in order to better understand the best approach.

Estimations of the extent of HIV disease in Sub-Saharan Africa are that 26 million people are currently infected of which the total number of children is 2.1 million. Worldwide it is thought that 2.3 million children are infected so it can be seen that the majority reside in Africa. In South Africa, we have a minimum of 250 000 HIV infected children aged less than 14yrs of age with only 15 000 on highly active anti-retroviral therapy (HAART) at present. Currently 40-60% of all paediatric admissions to hospital may be HIV related. HIV associated renal disease, is not yet well documented among children -especially from Africa -but now with the growing availability of HAART, this information has become more important for appropriate management. HIV renal disease presents in many forms, including including HIV-assoc nephropathy (HIVAN) and HIV Immune Complex Kidney disease (HIVICK) amongst others.

Questions have now been raised as to whether a screening program should be introduced as HAART, despite side effects and drug interactions, has revolutionised management if HIV infection detected early enough. Transplantation which was thought previously to be an absolute contraindication and potential waste of valuable resource is now possible, provided there is maintenance of HAART, HIV viral load is undetectable for >3 mths and CD4 >200cells/muL. There remains concern about feasibility in children with increased rejection, reduction of calcineurin inhibitors and infections such as recurrence of hepatitis C post-transplant. Despite these concerns, studies in adherent adults have clearly shown that adult patients with HIV infection do better following transplantation than on dialysis. Of concern, are some studies, showing that certain black patients may have a genetic predisposition to HIV infection. Overall, transplantation can be successful in these patients provided the HIV disease is under control. However, HIV disease -including renal disease -remains a major problem in Sub-Saharan Africa due to limited resources and lack of availability of drugs, where other health priorities may prevail. Background. Previous studies suggest that HIV-1 induces dysfunction and/or injury of endothelial cells, leading to the systemic release of Fibroblast Growth Factor -2 (FGF-2). To date, the role that circulating FGF-2 may play in the pathogenesis of childhood HIVAN is not clearly understood.

Objective. Here we sought to determine the potential role of circulating FGF-2 in the pathogenesis of HIVAN using wild type (WT) and HIV-Tg 26 mice. Methods and Results. To determine whether circulating FGF-2 induced ultrastructural changes in renal glomerular endothelial cells and podocytes, we injected human recombinant FGF-2 daily for 10 days into FVBN WT and HIV-Tg 26 mice (n=4 in each group). By electron microscopy we found that FGF-2 induced endothelial swelling and mild fusion of the foot processes in WT mice. These lesions were more severe in HIV-Tg 26 mice, which showed enlargement of podocytes, protein reabsorption droplets, significant fusion of the foot processes, and collapsing glomerulopathy. Subsequently, to confirm these findings in a different experimental model system, we used recombinant adenovirus carrying a secreted form of human FGF-2 (Ad-FGF-2). Four to five weeks old HIV-Tg 26 mice without evidence of abnormal protenuria (urine protein/creatinine ratio (UP/UC) <10), and their wild type littermates were injected with 5x10 8 plaque forming units (pfu) per mouse of Ad-FGF-2 or control Ad-lacZ vectors through the retro-orbital (r. o.) venous plexus (n=6 per group). All mice were followed for three weeks. All HIV-Tg 26 mice injected with rAd-FGF-2 developed heavy proteinuria (UP/UC >40). In addition, 50% showed elevated BUN levels (>25 mg/dl) and renal histological lesions typical of HIVAN. In contrast, WT mice, developed transient and moderate proteinuria (UP/UC <40), without renal failure or permanent renal damage. The number of animals with proteinuria in HIV-Tg 26 mice injected with Ad-lacZ group was consistent with the natural history of the renal disease progression. Control WT mice injected with Ad-FGF-2 developed mild proteinuria (40%) that returned to normal values14-21 days after the injection. FGF-2 induced microcystic tubular dilatation and recruitment of mononuclear cells both in WT type and HIV-Tg 26 mice, although the changes were more significant in the later group. Conclusion. Taken together, these results suggest that the accumulation of FGF-2 in the circulation of HIV-Tg 26 mice induces glomerular endothelial and podocyte injury leading to the development of heavy proteinuria, renal failure, and the typical renal histological features of HIVAN. We conclude that the elevated levels of FGF-2 in the circulation of HIV-infected children may be a significant risk factor for the development and/or progression of HIVAN.

Human Immunodeficiency Virus associated nephropathy (HIVAN) is the third leading cause of kidney failure in young African American adults in the United States. The prevalence and natural history of the disease in children is not well documented. We have examined our experience in 315 children, aged 2 months to 22 years (mean age 9.4±0.3 years) with predominantly perinataly acquired HIV-1 infection from their mothers. Since 1998, 286 of these children have been evaluated routinely for evidence of renal disease with quantitative assessment of proteinuria by random urine protein to creatinine ratios (Upr/cr). Renal functional studies included serum creatinine with estimation of glomerular filtration rate (eGFR), urinalyses, renal scintigraphy, ultrasound and renal biopsy when possible. The patients were divided according to their level of proteinuria. Those with nephrotic range proteinuria (Upr/cr>1.0) were designated as HIV-NS (N=32; 11%). Those with persistent intermediate range proteinuria (Upr/cr: 0.2<1.0) were designated as HIV-PP (N=62; 22%). Those with no proteinuria (Upr/cr<0.2) were designated as having no nephropathy (HIV-NoN; N=192; 67%). The great majority of patients were treated with highly active antiretroviral therapy (HAART), although those with HIV-NS had less time on treatment when their proteinuria was discovered. Moreover, the virulence of the HIV infection as measured by viral load (VL) was significantly greater in those patients with proteinuria. Also, viral load correlated positively with degree of proteinuria (r=0.5; p<0.0001). Mortality as shown by Kaplan-Meier survival curves was significantly greater in the HIV-NS group as compared to the PP and NoN groups. Renal failure occurred only in the group with nephrotic range proteinuria. During the past 25 years we have dialyzed 27 children with HIV infection in our end stage renal disease (ESRD) program for a total of 660 patient dialysis months. Since 1999, all patients are managed on hemodialysis due to the high occurrence of fungal peritonitis in our initial experience. Survival has improved remarkably during the past 10 years with a median survival of 35 months (range 4 to 125 months). The next stage is to begin renal transplantation in those patients with adequate control of the HIV infection. Aim: To determine the spectrum of severe renal disease in our HIV infected children; excluding severe sepsis and septic shock syndromes. Indications for their referral, renal biopsy and histology relating to outcome. Methods: Retrospective analysis of all children referred to the paediatric renal service from the general wards and HIV clinic from January 1996 to December 2005. Analysis includes age of presentation, sex, nutritional status, symptoms, renal function, histology, associated diseases including infections and follow-up. Results: Total of 60 children with a mean age of 6.6±0.7 years with a male: female ratio of 1:1.3. There was an overlap of symptoms but the commonest presenting symptom was haematuria in 50%, severe urinary tract infection and pyelonephritis in 23%, anasarca with or without any nephrosis in 33%, acute renal failure in 20%, chronic renal failure in 5%, severe electrolyte disturbances in 5%. Renal Biopsy was performed in 52 (86.7%) children. Histogically 50% had immune complex disease (ICD) of which 65.1% had lymphoid interstitial pneumonitis (LIP).11.5% had FSGS of which one had LIP but also had ICD, 11.5% had severe interstitial nephritis, associated infectious changes in 11.5% and ATN in 5.8%. One patient each had minimal change, MPGN, abdominal Kaposi sarcoma and kidney/bladder stones. 33.3% had or were treated for pulmonary tuberculosis. Mean follow-up was 12±12.9 months. Death occurred in 16.7% (10). All patients with FSGS with some renal dysfunction and severe sepsis demised. Conclusion: Despite the high burden of HIV disease, severe renal complications have a low prevalence. Good correlation of ICD and LIP (65.1%) but prognosis is good. Pulmonary Tuberculosis and infection is the main complications resulting in high mortality in nephrotic syndrome with FSGS. HIV associated nephropathy (HIVAN) is one of the most common causes of renal failure in HIV seropositive African Americans. In the USA, HIVAN has become the third leading cause of end stage renal disease (ESRD) in African Americans over the age of 20. While the introduction of HAART has decreased both the mortality and infectious complications of HIV infection, the incidence of HIVAN has reached a plateau and has not decreased. With reduced mortality, the prevalence of seropositive patients in the ESRD program continues to increase dramatically. The histopathological findings of HIVAN include focal segmental glomerulosclerosis of the collapsing variant combined with microcystic tubule dilatation. The most common other diagnosis is mesangioproliferative glomerulonephritis associated with Hepatitis C infection, a common comorbid condition. Typical features of HIVAN include renal enlargement and echogenicity by ultrasound analysis. Microscopic findings include coexistent microcystic tubule dilatation and glomerular involvement. Usually there is mild to moderate tubulointerstitial inflammation, interstitial edema, and fibrosis as well. Glomerulosclerosis is usually focal and segmental with collapse of the glomerular tuft and hypertrophy of visceral epithelial cells. HIVAN is caused by renal epithelial infection by HIV-1 in a susceptible host. Clearly there are genetic factors, based on the racial predilection of this disease. Patients with HIVAN are 5.4 times more likely to have a relative with renal failure. In susceptible individuals, HIV infection induces renal epithelial proliferation and apoptosis. The kidney represents a tissue-specific compartment in which HIV-1 can replicate in a previously unrecognized reservoir. While HIVAN is not currently considered to be an AIDS-defining condition, patients with HIVAN should be treated with HAART. In some instances, HAART has completely reversed the disease process, although it does not rid the kidney of virus. Thus, in patients with HIVAN, the kidney is a true reservoir for replication competent HIV. Whether this occurs in other forms of renal disease associated with HIV infection or in patients without renal disease remains to be determined. Prenatal administration of dexamethasone causes hypertension in rats when they are studied as adults. Renal sympathetic nerves directly innervate renal tubules and blood vessels and plays a role in the regulation of glomerular filtration rate and renal sodium excretion. We examined if renal nerves play an a role in mediating the hypertension in prenatal programming. Pregnant Sprague-Dawley rats were injected daily with intraperitoneal dexamethasone between 15 th and 18 th day of gestation. Renal norepinephrine concentration was measured at 3 weeks of age. Renal denervation was preformed at age 6 weeks of age in control and prenatal dexamethasone treated rats and blood pressure was measured at age of 8 weeks. Renal norepinephrine concentration was 338±25 ng/gr in controls and 591±82 ng/gr in the group that received prenatal dexamethasone (p<0.05). Systolic blood pressure at 8 weeks of age was 124±1 mmHg in sham operated controls, 122±5 mmHg denervated controls (p=ns). Blood pressure was elevated to 133±1 mmHg in dexamethasone treated sham operated group (p<0.05), but was normal at 115±1 mmHg in the dexamethasone treated denervation group. In conclusion, prenatal dexamthasone results in elevated renal norepinephrine levels. Bilateral renal denervation normalized the systolic blood pressure in rats that received prenatal dexamethasone. These data are consistent with the renal nerve playing an important role in mediating the hypertension in prenatal programming by dexamethasone. Objective: Evaluation of clinical outcomes in surgically treated children with renovascular hypertension (RVH). Methods: 35 RVH patients treated surgically at a single centre between 1979 and 2005 were retrospectively reviewed: 63% were male, 0.4-17.9 (median 7.6) years of age, with systolic blood pressure (SBP) 141 mmHg (105-300 mmHg). Results: Bilateral renal artery stenosis was present in 53%, midaortic syndrome(MAS) in 40%, intrarenal disease in 49% and coexisting cerebral disease in 24% of patients. Surgical procedures (N=47) included: a) nephrectomy (N=18), b) autologous surgery for both aortic reconstruction (N=1) and renal revascularisation (N=15) (renalartery reimplantation (N=4), renal bypass (N=9) and autotransplantation (N=2)) and c) synthetic graft interposition for renal revascularisation (N=6), aortic reconstruction (N=6) or both (N=1). The majority (92%) of patients who received synthetic grafts had vascular anatomy too complex for autologous surgery. Technical failure leading to secondary nephrectomy occurred in 3 patients. Postoperative complications were haemorrhage (N=5), septicaemia (N=4), and chylous ascites (N=1). There were no operative deaths. Patients from the UK were followed up for 5.1 (0.05-16) years. SBP post-surgery improved (116 mmHg, range 90-160 mmHg, p<0.0001). Outcomes were normal SBP without treatment (52%), improved (34%) or unchanged SBP (14%). Reduction of SBP led to loss of contralateral kidney in 1 patient. 10 children required re-interventions (15 angioplasties and 6 surgical procedures) for progressive disease (N=6), narrowing of the synthetic graft (N=4) and re-stenosis of the autologous bypass (N=2). Conclusion: RVH is a progressive disease of extensive nature. Surgery benefited 86% of children when performed in conjunction with conservative therapy and, if indicated, interventional radiology.

H. Wong 1 Unlike adults with predominant primary hypertension (HTN), the majority of children diagnosed with HTN traditionally suffered from secondary forms of HTN. However, substantial changes have occurred to the demographics of pediatric population over the past 20 years. In addition, our definition, awareness and understanding of children with hypertension has also changed. We therefore retrospectively reviewed the current causes of HTN in children followed in a single tertiary care pediatric nephrology referral center between January 2003 and December 2006. Patients who were either diagnosed with or treated for HTN at the time of their last visit where included. Gender, height, weight, age at the time of diagnosis, causer of HTN and casual blood pressure were recorded. Out of 1554 patients, 399 (25.7%) were diagnosed with HTN. The majority were males (n=249, 62%). Median was 10 years (1 month-18 years) age at time of diagnosis and 13.4 years (1.7 months-19 years) at time of the last follow-up. Secondary HTN was the most common cause of pediatric HTN (n=329, 82%) followed by primary (n=51, 13%) and then white coat (n=19, 5%). Renal HTN was the most common cause of secondary HTN (307/329, 93%). For patients referred initially for assessment of HTN (n=137), primary (n=43, 31%) and secondary (n=41, 30%) were the two most common diagnosis followed by normotension (n=38, 28%) and white coat HTN (n=15, 10.9%). Twenty two (5.5%) patients were diagnosed before the age of 1 year. Out of 23 renal transplant patients, 18 had HTN (78%). Renal HTN remains the most common cause of pediatric HTN overall and continues to represent a large portion of children referred for HTN. All children suspected of having HTN should continue to have thorough investigations of renal disease to identify the underlying cause.

M. Sinha 1 , C. Booth 1 , J. Simpson 2 , N. Dalton 3 , S. Qureshi 2 , C. Reid 1 , S. Rigden 1 1 Evelina Childrens Hospital, Guys and St. Thomas's NHS Foundation Trust, Department of Pediatric Nephrology, London, United Kingdom 2 Evelina Childrens Hospital, Guys and St. Thomas's NHS Foundation Trust, Department of Pediatrics Cardiology, London, United Kingdom 3 King's College London, Department of Medicine, London, United Kingdom Background: Hypertension (HT) is a frequent complication in paediatric TX patients. The evolution of end organ damage and its relationship to HT in these patients is not well described. Aim: To study the predictive value of an abnormal 24-hour ABP profile for end organ damage. Methods: Patients underwent simultaneous casual blood pressure (CBP), ABPM, echocardiogram (LVH if LVMI >38g/m 2.7 ) and ECG assessment, with measurement of several biochemical cardiovascular risk markers. CBP data for 18-months prior to study date was analysed as time averaged z-score. Results: We present initial results of a 5-year prospective study. 22 patients (16 male) aged 12.7y±3.4 (mean±sd) and 5.9y±2.6 since TX were studied. On the day of study all patients had normal CBP. 73% had LVH of whom 65% had abnormalities on ABPM. Overall, 55% patients had both abnormal ABPM and LVH. 45% had other findings: 10% abnormal ABPM but no LVH; 10% normal ABPM but no LVH; 25% normal ABPM and LVH. Data were analysed for differences between 2 groups of patients, with and without LVH. BP alone was significantly associated with increased LVMI. Time averaged CBP was normal in all patients although differed significantly between the 2 groups: systolic BP z-score [mean (CI)] 0.27 (0.57, -0.03) with LVH; -.31 (-0.09, -0.54) without LVH. There were significant differences by ABPM criteria relating to several components of the ABPM profile including mean arterial pressure, systolic and diastolic BP load. No difference was found between the groups for Hb, Ca*PO4 product, iPTH and cGFR. Conclusions: We have found the majority of our renal transplant patients have normal CBP but have abnormal ABPM in association with LVH. This suggests better control of hypertension should be achieved in patients who have abnormal ABP profiles and LVH. A new group of patients with normal ABPM but LVH has also been identified.

Background: Obesity is an independent risk factor for renal failure. Therefore, we compared the body composition of pediatric nephrology patients with the general child population over two decades. Methods: 6, 575 patients with a mean age of 9.5±4.2 years were studied. In 4, 595 patients (70.0%), sufficient data were available to analyze body composition. Body composition was measured as body mass index (BMI) Z-score because of the age dependency, calculated on the basis of data from the National (USA) Center for Health Statistics (2000) . Results: Enuresis (24.88%), hematuria (16.45%), recurrent urinary tract infections (11.98%) and proteinuria (11.17%) were the most common diagnoses. The BMI Z-score of the pediatric nephrology patients increased significantly from 0.33±0.47 in 1985-1991 to 0.72±1.06 in 1992-1999 and 1.27±1.54 in 2000-2006. While the rate of this increase was not statistically different from that seen in the normal population, they consistently demonstrated a significantly higher BMI Z-score (average +0.545) over time. Nephrotic edema, non-nephrotic proteinuria and hypertension were not confounding factors. Conclusions: Patients seen in our pediatric nephrology service over two decades had a higher BMI than the average child population. This implies that these patients are at even greater risk for development of chronic kidney disease later in life. We recommend therapeutic intervention to address this potentially modifiable risk factor. Objective: B cell dysregulation is believed to be involved in the development of childhood-onset systemic lupus erythematosus (SLE). There is limited evidence regarding efficacy and safety of interventions targeting B cell in children. In our study we evaluated efficacy and safety of B lymphocyte depletion therapy. Methods: Data of 20 children (15% male) with SLE aged 14.1 years (6.1-16.2) treated with rituximab in a single centre were retrospectively reviewed. Biochemical parameters were evaluated before and after treatment, and the normalisation of the parameters was assessed as a primary outcome. Results: Prior to rituximab therapy all patients received extensive immunosuppressive agents. Indications for rituximab therapy were chronic (N=13) or acute illness, in either relapsing SLE (N=3) or first presentation (N=4). Rituximab 750 mg/m 2 was intravenously administered twice within a 2-week period in combination with cyclophosphamide. Patients were followed up for 1.5 years (0.1-3.6) . No serious side effects were seen, except for viral infections such as herpes zoster (N=5). All patients with high creatinine (N=5; 226±99 mmol/l) prior to rituximab showed a decline within 2 months (mo), achieving a stable level by 8 mo (69±14 mmol/l, p<0.03). All patients with hypoalbuminaemia (N=12; 28.6±4.2 g/l) improved (5 mo: 36.1±6.4 g/l, p<0.001). Low C3 level (0.40±0.12 g/l) as seen in 12 patients prior to treatment resulted in an increase up to 5 mo (0.77±0.24 g/l, p<0.002). A decline of previously high anti-dsDNA (N=13; 162±163 IU/ml) was observed in all patients (5 mo: 56±62 IU/ml, p<0.02). Conclusion: Rituximab is safe and effective when used in combination with standard immunosuppressive agents. Further prospective studies are essential to evaluate the longterm safety of the drug.

Outcome of Severe Henoch-Schönlein Purpura Nephritis Treated with Longterm Immunosuppression M. Shenoy, M. Bradbury, L. Lewis, N. Webb Royal Manchester Children's Hospital, Department of Nephrology, Manchester, United Kingdom Aims: To look at the long-term outcome of all children with severe Henoch-Schönlein purpura nephritis (HSN) treated with long term immunosuppression in a single centre over a ten year period. Patients and methods: Retrospective review of the records of 27 children (19 male) with ISKDC grade 3b, 4, 5 and 6 HSN managed at our institution from 01/01/92 to 31/12/01 Results: The mean age at presentation was 9.8 years (range 3.6-15.8 years). The median estimated glomerular filtration rate (eGFR) at presentation was 91 ml/min/1.73 m 2 (IQR 51. 5-96.6 ) and urine protein: creatinine ratio (UP: UC) was 556 mg/mmol (IQR 292-1363). The indication for biopsy was nephrotic syndrome in 9, nephrotic range proteinuria in 7, sub-nephrotic range proteinuria in 3, acute nephritis in 6 and nephritic-nephrotic syndrome in 2. A total of 25 patients were treated with weaning dose of steroids, of whom 22 were also commenced on long-term azathioprine (mean duration 8.9 months). 18 of these children received an 8-12 week course of oral cyclophosphamide (2-3 mg/kg/day) prior to azathioprine therapy (2-3 mg/kg/day). Outcome: After a mean follow-up period of 7 years, 10 (37%) have made a complete recovery, 11 (40.7%) have persistent proteinuria but normal eGFR, 2 (7.4%) have persistent proteinuria and are on anti-hypertensive therapy with normal eGFR and 4 (14.8%) have progressed to ESRD. Older age at presentation was the only independent risk factor for poor outcome (12.8 years vs. 8.9 years, p=0.005). Conclusions: Despite treatment with cyclophosphamide, long-term steroids and azathioprine, a majority of children with HSN grade -3b on initial biopsy have persistent renal abnormalities on long term follow-up. Only older age at presentation was associated with poor outcome.

Background: Resent advances in podocyte biology indicated that the main cause of the heavy proteinuria in nephrotic syndrome (NS) is a dysfunction of slit diaphragm. On the other hand, the classical charge selective barrier is not likely to have a place in slit diaphragm. Therefore we reevaluated the charge selective barrier function in NS and chronic glomerulonephritis using recently established charge selectivity index (CSI; Takahashi et al, Pediatr Res 59: 336, 2006) in comparison with Dent disease. Patients and Methods: CSI is a clearance ratio of IgG (Stokes Einstein radius 49-60, pI 4.5-9.0) and IgA (Stokes Einstein radius 61, pI 3. 5-5.5) . The assay of serum and urinary IgG and IgA was performed using laser nepherometry and enzyme immuno-assay. In order to evaluate the CSI of normal glomerular filtrate, we measured the CSI of Dent disease. The urine of Dent disease is considered to be a concentrate of filtered protein from normal glomerulus, without having a process of tubular protein reabsorption. Thirty eight patients with podocyte diseases (Focal and segmental glomerulosclerosis 4, Finnish type congenital nephrotic syndrome 1, Steroid sensitive nephrotic syndrome 33), 75 patients with chronic glomerulonephritis (IgA nephritis 41, Henoch-Schönlein purpura nephritis 21, mesangiocapillary glomerulonephritis 5, Alport syndrome 8) and 8 patients with Dent disease, were analyzed. Results and conclusion: CSI (mean±SD) of podocyte disesses, chronic glomerulonephritis and Dent disease was 1.12±0.25, 0, 42±0.31 and 0.18±0.04 respectively. The results apparently indicated that the charge selective barrier of GCW is working strongly in normal glomerulus, less strongly in podocyte diseases and not working in chronic glomerulonephritis. Objectives: NPHS2 mutations have been reported in familial and sporadic SRNS. We investigated the prevalence of NPHS2 mutations among South-East Asian Chinese and their association with clinical outcomes. Methods: Genomic DNA from 29 patients with primary sporadic SRNS (mean age at onset 5.4±4.0 years, range 0.58-12.0 years) and 45 cord blood controls were screened on all 8 exons and exonintron boundaries using direct sequencing. Results: A missense heterozygous 871C>T mutation in exon 7 was identified in only one patient. Polymorphisms 954T>C and1038A>G in exon 8 were detected in both groups. In the patient group, the genotypic frequency of TT, TC, CC at position 954 was 0.24, 0.55 and 0.21, and AA, AG and GG at position 1038 was 0.86, 0.14 and 0 respectively, consistent with Hardy-Weinberg expectations. There was no significant difference in allele frequencies between patients and controls. Using binary logistic regression analysis, individual polymorphisms did not appear as informative predictors of poor clinical outcome, defined as persistent proteinuria or renal failure (p>0.05). On analyzing composite genotypes, carriers of at least a copy of the 954C allele were significantly associated with poor outcome (p=0.047, OR=12.7, 95% CI: 1.03-157), while heterozygotes for 1038A>G were associated with good outcome (p=0.048, OR=0.06, 95% CI: 0.004±0.979), suggesting possible interactions between the polymorphic sites. Further analysis showed that the genotypic combination of 954TC/CC with 1038AA was more likely to have a poor clinical outcome. No significant linkage disequilibrium was detected between the two polymorphisms. Conclusion: The concomitant occurrence of at least a copy of the 954C allele and the 1038AA genotype may be associated with poor clinical prognosis in SRNS but larger studies are needed to confirm these findings. Renal hypodysplasia (RHD) is characterized by a reduced kidney size and/or maldevelopment of the renal tissue following disturbed organogenesis. Numerous deletion mouse models of developmental genes have been established presenting with anomalies of the kidneys resembling RHD, among these the knock-out of Bmp4 and Six2. Here, we report on the first human mutations in BMP4 and SIX2 identified in children with RHD, among these three different mutations in BMP4 in five unrelated patients (Ser91Cys, Thr116Ser, Asn150Lys) and three different mutations in SIX2 also in five unrelated individuals (Leu43Phe, Pro241Leu, Asp276Asn). Overexpression assays in zebrafish demonstrated that ventralization and dorsalization caused by Bmp4 and Six2 overexpression, respectively, could be diminished after overexpression of mutant constructs expressing the human mutations identified. Morpholino knock-down of zebrafish bmp4 and six2.1 reveals specific roles of these genes for pronephric development, affecting the expression of wilms tumor-1 (wt1) and glomerular development. RNA analysis of COS7 and HEK293 transfected with different BMP4 constructs showed a lower level of mRNA abundance in Bmp4 mutants, indicating a possible negative feedback of the mutants on their own mRNA expression and/or stability. Nonreducing Western analysis revealed that S91C-Bmp4 forms alternative protein complexes as compared to wildtype-Bmp4, due to the formation of extra disulfide bonds. These studies implicate Six2 and Bmp4 as important players in the development of the renal system, and suggest that defects in these proteins could affect kidney development at multiple stages leading to the congenital defects observed in RHD patients. Apoptosis is important in normal renal development in which regulation of cell numbers is critical. Studies have shown that apoptosis occurs in non-cystic tubules in pre-uremic PKD kidneys, thus providing the mechanism whereby expansion of cysts is accompanied by loss of normal nephrons. To date, it is unclear which initiating factors (intrinsic, through mitochondrial damage or extrinsic, through ligand activation of death receptors) are responsible for apoptosis in PKD and whether they are the same in AD-and ARPKD. Aim: To elucidate the sequence of activation of intracellular apoptotic pathway(s) in both AD-and ARPKD. Methods: Proteins were extracted from tissues of human AD-and ARPKD kidneys and normal adult (NHK) and fetal kidneys (HFK). Quantitative Western immunoblot analysis was carried out for 7 markers of intrinsic and extrinsic apoptosis. Immunohistochemical staining for these markers was performed on tissue sections of the same kidneys. Results: Markers of extrinsic apoptotic pathways, caspases 8 and 10, were significantly increased in AR-and in ADPKD tissue by comparison to NHK and HFK tissues. These increases were seen in early stages of ADPKD and were more pronounced later in the disease. For the intrinsic pathway, caspase 9 and Bid were increased in HFK tissue, but unchanged in AD-and ARPKD tissue compared to NHK tissue. Staining for caspase 9 was found in HFK, but was absent in all other kidney tissues. Staining for caspase 8 was seen in early ADPKD and endstage (ES) ADPKD as well as in ES ARPKD. Caspase 3 was identified as the main executing caspase of fetal development and ADPKD, but wasn't seen in ARPKD, where caspase 7 predominated. Conclusion: Induction of extrinsic pathways of apoptosis predominates in PKD and occurs early in the disease process in ADPKD, but only later in ARPKD. Intrinsic apoptosis predominates during development.

Intrauterine growth restriction (IUGR) is a risk factor for an aggravated course of renal diseases in later life. The influence of postnatal factors, eg. accelerated catch-up growth, is not well understood. We therefore analysed the influence of postnatal nutrition after IUGR on the developement of later renal inflammation and fibrosis in the rat. IUGR was induced by low protein diet (8% vs. 20%) in pregnant Wistar dams. Litter size was reduced to 6 or 10 male animals in IUGR (LP6, LP10) and control animals (NP6, LP10), respectively. Animals were sacrificed on day 70. Mean arterial blood pressure was similar in all four groups. LP6 -(31.7±6.4 ml/h/100 g) and NP6 animals (37.68±16.6 ml/h/100 g) showed reduction of endogen creatinine clearance by 50% (vs. NP10and LP10) (p<0.001). Renal mRNA expression of IL6 (5, 7 x), TGFβ1 (1, 5 x) , Endothelin 1 (2, 7x) und Osteopontin (2, 3 x) was significantly higher in LP6 than in NP6. LP6 showed the highest glomerulosclerosis-score ((0.39±0.07) (vs. NP6 (0.1±0.07), LP10 (0.09±0.02) and, NP10 (0.03±0.02)) (p<0.01). As marker of extra cellular matrix expansion glomerular Collagen-IV deposition was significantly higher in LP6 (17.8±6.3%) (vs. NP6 (14.3±4.0%), LP10 (7.4±4.0%) and NP10 (7.2±1.9%)) (p<0.01). Postnatal nutrition modifies the consequences of IUGR in the kidney. Increased postnatal nutrition of the individual animal is associated with aggravated renal inflammation and fibrosis after IUGR.

Unilateral Renal Agenesis (URA): how Intensively do we Need to Investigate and Follow-up? S. Rhodes, A. Watson Nottingham University Hospitals, Children and Young People's Kidney Unit, Nottingham, United Kingdom A single kidney is one of the commonest urinary tract abnormalities in the general population. Concerns remain about long-term outcomes with a reduced nephron mass and hence intensity of investigations and duration of follow-up. We identified 52 cases with URA (ectopic and pelvic kidneys excluded) from our nephrourology database between 1985 and 2006. 38 (73%) occurred in males and 25 (48%) had left URA. 27 (52%) were detected antenatally with 12/27 (44%) recognised in the last 2 years. Median age of detection for postnatal URA was 7 mths (range 0.25-179 mths) with UTI (29%) as the main indication for ultrasound scan (USS). 60% patients were classified as simple URA with no associated abnormality and 40% as complex with problems such as vesicoureteric reflux (VUR)(21%), hydronephrosis or scarring. All cases reviewed had USS which showed compensatory hypertrophy in 25/52 (48%). 29/52 (56%) had DMSA scan and 24/52 (46%) micturating cystogram. Of those antenatally detected single kidneys with normal initial USS none had VUR, scarring, hypertension or proteinuria. These patients were discharged from follow-up at the median age of 6 mths (range 1-122 mths). All complex cases have continued under follow-up. Conclusions: Our data suggest that the incidence of antenatally detected URA may be increasing. Investigations need to be individualised depending upon the initial USS. The value of routine DMSA and MCUG in simple cases is questioned. Most of these patients can be discharged after adequate documentation of compensatory hypertrophy of the normal kidney, absence of proteinuria, normal blood pressure and renal function.

Autosomal Dominant PDK (ADPKD) in Childhood J. Crocker, P. Wornell, P. Acott IWK Health Centre/Dalhousie Univeristy, Division of Nephrology, Halifax, Canada Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic kidney disease with 1 in 6 adults progressing to end-stage renal disease (ESRD). A program for intervention in childhood at presentation with ADPKD was developed and instituted in 1992. Our long-term objective is to modify clinical parameters that may contribute to risk of development of ESRD in adulthood. Seventy children with ADPKD (average age 11.47 yr) were followed, of which 10 (14%) had nephromegaly +/-cysts on antenatal ultrasound. Modifiable risk factors were common including hypertension (22%), hyperlipidemia (54%), and proteinuria (7%). ACE inhibitors were first line therapy for proteinuria and/or hypertension. ACE inhibitors may modify cyst progression so they have been made available to non-hypertensive children as well. Most patients with hyperlipidemia responded to dietary intervention with one patient developing gallstones. In the past 5 years we have focused on renal calculi, as this is a known risk for a subgroup of adults with poor prognosis. We noted 14 patients (20%) have glycinuria, which is a precursor to oxaluria. Four patients have passed calculi with two of these being diagnosed by genetic linkage analysis for ADPKD without radiographic cysts present. Cerebral vascular studies of 14 patients with severe headaches revealed two with vascular structural anomalies. All adolescent females received counseling regarding appropriate contraception and their pregnancy risks of hepatic cyst progression. An early intervention program targeting modifiable risk factors of ADPKD patients during childhood and adolescence may modify adult renal failure risk in this population. Background: Techniques of chronic infant dialysis have evolved during the past 2 decades but morbidity and mortality are not well described. Methods: A retrospective review was performed on 45 infants -18 months of age with end stage renal disease (ESRD) treated with maintenance dialysis during the past 23 years. The experience was divided into ERA 1 (1983 ERA 1 ( -1994 (N=23) and ERA 2 (1995 ERA 2 ( -2006 . Dialysis modality, morbidity, and long term survival were assessed and compared between the 2 Eras. Results: All patients were begun on peritoneal dialysis (PD). There were 22 males and 23 females. Age at initiation of dialysis was 4, 5 months. The predominant diagnoses were dysplasia/obstructive uropathy (N=24), autosomal recessive polycystic kidney disease (ARPKD) (N=10), congenital nephrotic syndrome (CNS) (N=7), other (N=4). Overall survival is 38% (17/45) with current age of survivors ranging from 5 months to 23 years. Mortality between Era 1=70% and Era 2=55% was not significantly different. Fifteen (33%) survived to receive a kidney transplant. Overall median survival is 3.1 years (Era 1=3.5 years; Era 2=3.1 years; p=0.97). Conclusions: Although long term survival is possible in infants with ESRD, mortality and morbidity remain high. Improved technologies for automated PD should address the needs of the infant <6 kilograms. Joubert syndrome and related disorders (JSRD) are a group of autosomal recessive conditions characterized by a complex neuroradiological malformation resembling a molar tooth on imaging. Clinically, JSRD are characterized by overlapping phenotypes presenting neurological signs and variable involvement of other organs such as kidneys (mainly nephronophthisis -NPH), retina and liver. Seventy-nine Italian JSRD patients from 63 unrelated families were recruited in pediatric nephrology and neurology centers. Medical records and brain MRI were reviewed. Patients without chronic renal failure (CRF) underwent measurement of their glomerular and tubular function, a DDAVP urine concentration test and a renal ultrasound. Retinal examination was performed in most patients. Seven patients younger then 18 years had normal renal function but were not fully tested. Of the remaining 72 cases, 44 had no evidence of renal disease, 16 had developed CRF mostly in their second decade of life, and 9 were younger then 11 years of age and had urinary concentration defects, of whom 5 also had hyperechogenic kidneys by renal ultrasound. When comparing this latter group with age-matched JSRD patients, no other tubular function abnormality was detected. In 13 multiplex pedigrees, no discrepancies in renal involvement between affected family members was observed. Retinal involvement was significantly associated with renal disease. Conclusions. Evidence of interstitial renal disease was observed in one third of Italian patients with JSRD. Renal involvement should always be suspected in these patients, particularly if they have evidence of retinal dysplasia or other family members with symptoms related to NPH. These patients should be assessed with a urine concentration test. We examined the course of 49 children with 56 primary obstructive megaureters (POM) treated in our hospital from 1994-2006. POM occurred more often in boys (71%, p<0.01) and on the left side (67%, p<0.05). 43 POM (77%) were only treated conservatively. Four underwent immediate surgery following the first MAG3 renography. One of these was nephrectomized after unsuccessful urinary diversion and persistent renal hypertension. Of the 52 kidneys primarily managed conservatively, 9 needed a ureterocystoneostomy later on due to increasing obstruction. Surgical correction of POM required a mean of 15 days of hospitalization (incl. temporary urinary diversion, removal of catheters and treatment of complications). One child required surgical revision of early post-operative ureteric stenosis. Urinary tract infections (UTI) were a common complication (n=66, mean 1.3 per patient). As UTIs occurred mainly in infants, hospital admission was commonly required (45%). Only 14 children never acquired a UTI (29%). Eight patients had a poor outcome as defined by partial kidney function <40% on the affected side (n=6), atrophy on final ultrasound (n=3) or nephrectomy (n=1). The most potent predictor of reduced unilateral kidney function was a small kidney present from birth. Secondary kidney growth failure occurred only in one case. The initial degree of obstruction on renography, but not the degree of hydronephrosis or size of megaureter predicted outcome. Also, prenatal diagnosis of POM, surgical treatment and the occurrence of UTIs showed no association with outcome. In summary, the long-term prognosis of POM appears favorable. Adverse outcomes were more closely related to congenital kidney size deficit than to the degree of obstruction. Surgical interventions and the high UTI incidence led to significant hospitalization times.

R. Bhimma, M. Adhikari, K. Asharam University of KwaZulu-Natal, Maternal and Child Health, Durban, South Africa Background: Steroid resistant (SR) forms of NS have a poorer outcome in blacks compared to other racial groups. Methods: 223 children with SRNS 1-16 years old were analysed retrospectively for the period 1976-2004. Treatment schedules included oral cyclophosphamide with prednisone only (n=90); prednisone on alternate days with methylprednisolone and oral cyclophosphamide (n=117); oral prednisone on alternate days, 3 doses of intravenous methylprednisolone on alternate days and monthly doses of intravenous cyclophosphamide (n=10) or cyclosporine adjusted to a trough level of 150-200 mg/ml (n=6). We compared the clinical, biochemical characteristics and outcome of these children using different forms of therapies. Results: 183 (82.1%) underwent renal biopsy.84 (45.9%) were Indian and 99 (54.1%) were black. 66 (36.1%) had minimal change NS, 66 (36.1%) had focal segmental glomerulosclerosis (FSGS), 15 (8.2%) a proliferative form of NS, and 36 (19.7%) had other forms of NS. 58/84 (69.0%) Indian children biopsied were in complete remission and 29/40 (72.5%) with MCD who were treated with oral cyclophosphamide and prednisone only achieved complete remission. 32/40 (80%) Indian children not biopsied who received only oral prednisone and cyclophosphamide achieved complete remission. 20/99 (20.2%) black children who were biopsied achieved complete remission. None of the eight black children who were not biopsied given only oral cyclophosphamide and prednisone achieved complete remission. Conclusion: Since 80% of Indian children with SRNS responded to a trial of oral cyclophosphamide and prednisone but none of the black children did, we propose the use of oral cyclophosphamide therapy in non black children before embarking on renal biopsy.

MJ. Kemper, C. Moeller, N. Rink, M. Van Husen, DE. Müller-Wiefel University of Hamburg, Pediatric Nephrology, Hamburg, Germany Introduction: SSNS is often complicated by a refractory clinical course with frequent relapses and steroid dependency despite aggressive alternative immunosuppressive regimens. Since recent immunological findings suggest an alteration of not only T-but also B-cell immunity in SSNS (Kemper 2003 (Kemper , 2004 we hypothesized that that immunological targeting of B-cells with antibodies directed against CD20 (Rituximab) is able to maintain remission (RM) in treatment refractory patients with SSNS Methods: A total of six patients with complicated courses of SSNS had severe steroid-dependency and toxicity. All patients had previously been treated with cyclophosphamide, two patients relapsed on maintenance therapy with cyclosporine, one relapsed on additional levamisole and one on MMF. Treatment was initiated at a median age of 13 (range 11-15.6) years and RTX was given at steroid induced RM at a dose of 4x 375 mg/m 2 BSA within 4 weeks. Results: A complete B-cell depletion was induced for at least 5 months in all patients. RM could be maintained in all patients and steroid treatment could be discontinued after a median of 2.5 months (range 1-4.6) . Also CSA could be discontinued in the two patients on maintenance treatment. At current follow-up of 11.5 months (range 5-23.5) the two patients after CSA discontinuation relapsed after 8.7 and 12.7 months, respectively, but responded after steroid induced RM-to a second course of RTX. All other patients remained in remission off treatment so far. No significant clinical side effects were noted. Conclusion: In summary and conclusion, RTX seems to be a therapeutic option in complicated SSNS. Long-term follow-up and future prospective studies are necessary to further define the role of RTX in the treatment of refractory steroid sensitive nephrotic syndrome.

Efficient control of secondary hyperparathyroidism can be achieved by calcimimetics. They increase calcium sensing receptor (CaR) sensitivity to extracellular calcium. In R-568-treated uremic rats, proteinuria has been significantly reduced by calcimimetics. Thus, we examined the potential direct effect of R-568 on podocytes. The CaR was expressed in cultured immortalized podocytes (quantative rtPCR, western blot) and in podocytes obtained from healthy and subtotally nephrectomized rats (immunohistochemistry). Glomerular CaR abundance was increased by uremia and R-568. The CaR colocalized with the plasma membrane and intracellular filaments in cultured podocytes, but not with the caveolin 1-and 2-rich membrane fractions. We then studied the effect of R-568 on the mitogen-activated protein kinase (MAPK) family. JNK was not activated. P38 showed a biphasic response pattern, whereas ERK1/2 (and further downstream, p90 ribosomal S6 kinase) showed dose-(1-50 nmol/L) and time-dependent phosphorylation, resulting in the activation of the transcription factor cAMP response element binding protein (CREB). CREB phosphorylation induced Bcl-xL expression and BAD phosphorylation, both of which have prosurvival activity. Specificity was confirmed by addition of MEK 1/2 inhibitor U0126, which completely blocked R-568-induced CREB phosphorylation. FACS analysis revealed a significant, 50% decrease in puromycin-induced apoptosis in podocytes treated with R-568 for 48, 60 and 72 hrs. In conclusion, calcimimetics induced prosurvival gene expression in podocytes via MAPK, protecting them from apoptosis. Calcimimetics may have a direct renoprotective action beyond control of hyperparathyroidism in chronic kidney disease patients.

We report our experience with plasma therapy in a family of three sisters from whom two are homozygous twins (patients b and c), presenting a missense mutation of the exon 23 of the human complement factor H gene (HF-1). The factor H concentration has always remained normal and no systemic complement activation has ever been detected. In a ten years period, the followings have been observed: 1/ No use of plasma exchange lead to immediate ESRF of native kidneys (patient a); 2) conventional plasma therapy (10 sessions at presentation followed by repeated 10 ml/kg plasma infusions when relapse of hemolysis and thrombopenia) could not impede ESRF (patient b); 3) the use of intensive PE at presentation (daily PE (40 ml/kg FFP until plasma creatinine normalization followed by one PE/2w indefinitely) lead to a normal GFR 5 years after presentation despite 2 relapses (patient c); 4/ no prophylactic PE for Tx lead to immediate HUS relapse and transplant loss (patient 1); 5) prophylactic PE allowed a successful Tx in patient b (pl. creat 110 mcmol/l after 5 years); 6) early and intensive PE allowed complete normalization of several HUS relapses after Tx (patient b). Conclusions: in FH mutation-related atypical HUS, 1) intensive and indefinitely prolonged PE can allow a normal function of native kidney at long term; 2) prophylactic PE allows successful kidney Tx; 3) early and intensive PE allow reversion of HUS relapse after Tx. The success of plasma therapy is bound to the followings: A/ The use of PE and not plasma infusion. B/ The prolongation of daily PE after normalization of hemolysis parameters, and further prophylactic PE. C/ The use of PE prophylaxis from before TX. D/ A minimum PEs frequency of one/week in case of prophylactic treatment for TX. E/ Immediate intensification of PE frequency in case of relapse. Objectives of study: Heparan sulfates (HSs) are highly polyanionic sugar chains in the glomerular basement membrane (GBM) and have been reported to play an important role in the chargeselective permeability of the kidney. Alterations in HS expression have been reported in a number of renal pathologies. In this study, we evaluated if degradation of HS in the GBM resulted in proteinuria in rats, using a controlled in vivo approach. Methods: Heparinase III and neuraminidase were injected i. v. in 2-month old Wistar rats at t=0 hr and t=8 hr, and kidneys were removed at t=24 hr. Urine samples were taken at various time points. Cryosections were stained for HS using specific antibodies, and for HS stubs (generated by heparinase). In addition, HS was evaluated at the electron microscopical level. Neuraminic acid expression was analysed by peanut agglutinin lectin. The HS content in urinary samples was evaluated by agarose gel electrophoresis. Urinary neuraminic acid was studied by an enzymatic colorimetric assay. Presence of urinary albumin (proteinuria) was investigated by SDS-PAGE and by a competition ELISA. Results: Injection with heparinase III resulted in an almost complete absence of glomerular HS staining. Cupromeronic blue staining was also greatly reduced in the GBM, further indicating that HS was largely degraded. Staining for the HS proteoglycan core protein agrin was unaltered. In the urine a strong increase in HS was found, already at the first point in time of urine collection (2 hr after the first injection). However, no urinary albumin or other proteins could be detected at any point in time analysed. Injection of rats with neuraminidase resulted in a major increase of albumin in the urine. Conclusion: In conclusion, removal of HS from the GBM does not result in acute albuminuria, whereas removal of neuraminic acids does.

Introduction and methods: 192 children undergoing deceased (156) or living (36) donor kidney transplantation were randomized to receive tacrolimus, azathioprine, steroids and two doses of basiliximab (tas+b) or tacrolimus, azathioprine and steroids(tas). Previously reported six month follow-up biopsy-proven acute rejection rates were 19.2% (tas+b) and 20.4% (tas). Patient survival was 100% and graft survival 95% in both arms (Am J Transplant 2006; 6: 1666-72) . In this investigator-driven follow-up study individual outcome data were submitted annually to the coordinating centre. Results: Two year follow-up data were obtained for 144 (87.8%) of the 164 who completed the six month study. There was one death in the tas group occurring at month 20. There were 5 graft losses in the tas+b arm and 9 in the tas arm. All 5 graft losses in the tas+b arm occurred within the first 6 months. Kaplan-Meier estimates of 2 year graft survival were94.9% for tas+b and 89.5% for tas (p=0.28 Breslow Generalised Wilcoxon test). Episodes of biopsy proven acute rejection occurred in 23 in tas+b and 26 in tas, Kaplan-Meier estimates of freedom from rejection being 76.1% and 69.6% respectively (p=0.49). Renal function did not differ significantly between the two arms; the median (IQR) plasma creatinine levels were 90 (74-113) in tas+b and 96 (77-115) in tas (p=0.94). Similarly there was no evidence of a difference in either systolic or diastolic blood pressure between the two arms. There was one case of B cell PTLD in the tas+b arm at 11 months in addition to two cases in the tas arm previously reported in the 6 month study.

Conclusions: The addition of basiliximab to a regimen of tacrolimus, azathioprine and steroids does not appear to result in an improvement in either acute rejection rate or graft survival at two year follow-up. Further data collection is ongoing. Chronic renal dysfunction is a major complication after heart transplantation (HTx). The pathophysiology is not yet fully understood but is thought to be in part due to calcineurin inhibitor (CNI) toxicity, and reducing CNI exposure has become one of the main strategies aimed at ameliorating renal outcome in HTx recipients. We previously reported a significant improvement of renal function in 14 HTx children with biopsy-proven CNI nephrotoxicity and chronic renal failure, 1 year after the reduction of CNI dosage with a concomitant replacement of azathioprine by mycophenolate mofetil. We ought to determine whether this improvement was persistent after 3 years of follow-up, despite the histological lesions of chronic CNI nephrotoxicity. GFR evaluated by annual inulin clearance had improved from a mean of 46.5±9.6 ml/min/1.73 m 2 (range 34-60) at time of the switch to 77.6±6.0 ml/min/1.73 m 2 (range 54-102) (p=0.019) one year after (67% improvement), and remained stable at 76.4±18.2 ml/min/1.73 m 2 (range 50-102) (p=0.76) 3 years after the switch. Maximal urinary osmolality followed the same increase profile from 559±103 mOsm/kg before the switch to 762±122 at one year and 736±154 after 3 years (p=0.64). Meanwhile, the occurrence of serious adverse events such as infectious episodes, acute rejection and chronic allograft dysfunction as assessed by clinical examination, echocardiography and endomyocardial biopsies were not different from a control group of patients whose treatment was unchanged. No malignancy was observed in either group. In conclusion, reduction of CNI dosage and replacement of azathioprine by mycophenolate mofetil lead to a safe and long-lasting improvement of renal function in children with heart transplants and CNI-induced nephropathy. Previous studies have demonstrated reduced bone mineral density (BMD) in some patients with idiopathic hypercalciuria (IH). Reduced BMD during childhood may impact adult peak bone mass. Bisphosphonates employed in adults with IH and reduced BMD resulted in conflicting outcomes. We evaluated the effects of oral bisphosphonate, alendronate (Ale), in 3 patients with persistent IH and reduced BMD. Patients presented at ages 6, 12, 13 yr, with hematuria/dysuria, 2 had recurrent urolithiasis, and all had IH (UCa >4 mg/kg/24 hr). Despite maximal traditional Rx with low Na/high K diet, thiazides, K-citrate, IH persisted (5.6-12 mg/kg/24 hr). At ages 10, 16 and 14.5 yr, DXA showed reduced BMD, and Ale 10, 40 and 70 mg/once weekly was given for 15, 7 and 18 months, respectively. After 6 months of Ale, UCa decreased significantly compared to baseline (mean±SD, 3.0±1.9 vs. 6.3±1.8 mg/kg/24 hr, p<0.05). Compared to baseline, BMD Z scores 1 year after starting Ale improved at the spine (-1.1±0.4 vs. -2.3±0.6, p<0.05) and hip (-1.9±0.3 vs. -2.3±0.2) . The decline in UCa during Ale Rx correlated with the increased BMD Z scores in the spine (r=-0.98, p=0.01) and hip (r=-0.93, p<0.05). Height Z scores, serum creatinine, Ca, P, electrolytes and PTH remained normal throughout the Rx period and no further hematuria or new stones occured. In summary, Ale normalized UCa previously resistant to traditional Rx, eliminated urinary symptoms and improved reduced BMD in children with IH. The use of a single oral weekly dose appears adequate and safe. Larger prospective studies are needed to confirm these preliminary results.

In addition to its classical role in the regulation of calcium (Ca) and phosphate (PO 4 ) homeostasis, vitamin D has important immunomodulatory and anti-inflammatory effects, that in turn can influence atherosclerotic vascular disease. We studied the impact of vitamin D levels and inflammation on vascular structure and function in children on dialysis. 59 children (age 13.4±4.1 yrs) on dialysis (mean duration 1.1±0.9 yrs) were studied. All children received 1α-hydroxyvitamin D 3 (alfacalcidol) . Cumulative data on Ca, PO 4 and PTH, doses of PO 4binders and alfacalcidol were recorded.1, 25-dihydroxyvitamin D 3 (Vit D) and high-sensitivity CRP (hs-CRP) levels were measured by 125 I radioimmunoassay and ELISA respectively. All children had carotid intima-media thickness (cIMT), pulse-wave velocity and cardiac CT for coronary calcification. 23 (39%) children had Vit D deficiency (levels<40 pmol/L), 25 (42%) hadnormal levels (40±150 pmol/L) and 11 (18%) had high levels (>150 pmol/L). Vit D positively correlated with serum Ca, CaxPO 4 and alkaline phosphatase. Both cIMT and calcification showed a bimodal distributionpatients with Vit D levels <40 or >150 pmol/L were significantly more likely to have calcification or raised IMT than those with Vit D levels in the normal range. hs-CRP levels independently predicted cardiac calcification (p=0.02) but not cIMT. There was a strong inverse correlation between Vit D levels and hs-CRP (p<0.0001, r=-0.69). Patients with vitamin D levels<40 pmol/L and hs-CRP levels>10 mg/L had 6-fold greater calcification scores than subjects below these cutoffs.

In conclusion, Vit D deficiency is common despite treatment in children on dialysis. Vit D may be an important mediator of vascular damage both through its hypercalcaemic and anti-inflammatory actions. Severe growth failure remains one of the challenging problems in the care of children suffering from chronic renal failure (CRF). Although, rhGH has been proven to increase final adult height in prepubertal CRF patients only limited data on its efficacy in the pubertal age-range are available. In addition, the impact of the underlying renal disease and the mode of renal replacement therapy on final height in these patients remain unclear. We report on final height data of 240 (47 female) severely growth-retarded CRF patients (standardized height <-2 SDS; Database: KIGS Medical Outcomes, Pfizer). Mean age at start of rhGH therapy was 13.7±3.0 years, standardized height was -3.6±1.2 SDS and duration rhGH therapy was 4.6±2.5 years (range 1.0 to 14.2 years). At baseline 45% of the patients were on conservative treatment, 28% were on dialysis and 27% had a functioning renal allograft. In the whole study population mean standardized height was increased in the first treatment year and at attainment of final adult height by +0.4 SDS and +1.2 SDS, respectively (each p<0.0001 vs. baseline). Prepubertal children aged less than 12 years at start of rhGH therapy showed the best growth response (+1.5 SDS). In pubertal patients mean increase in standardized height was +1.2 SDS, whereas growth response in patients with delayed onset of puberty (>+2 SD) was significantly lower (+0.8 SDS; p=0.039 vs. other groups). The duration of rhGH therapy was positively associated with cumulative height gain. Growth response was significantly lower in patients on long-term dialysis and in patients with nephropathic cystinosis. Conclusion: RhGH therapy in severely growth retarded prepubertal and pubertal CRF patients results in an increased final adult height. Growth response is diminished in CRF patients with markedly delayed onset of puberty. Tightly regulated RANKL/OPG system is essential for normal bone remodelling. However, the exact roles of those osteogenic markers in uremic bone disease have yet to be defined. We therefore assessed the potential relationship of the RANKL/OPG system in bone biopsy proven secondary hyperparathyroidism (HPT) in dialyzed children. Methods: 40 patients aged 13±1years were on CCPD for 14±4 months. S-Ca, P, Alk P'tase, PTH, OPG and RANKL levels were measured. Bone biopsies were obtained after double tetracycline labeling and none of the patients were treated with vitamin D for four weeks prior to biopsy. Results: S-Ca levels were 9.2±0.7 mg/dl, P: 6.1±1.5 mg/dl, Alk P-tase: 401±297 U/l, PTH: 898±415 pg/ml. Bone biopsy findings revealed high turnover bone disease in 31 patients, 9 patients had normal bone formation rate (BFR). Mean OPG and RANKL levels were 4.46±1.46 and 0.66±0.81 pmol/l, respectively (reference control=OPG: 1.8; RANKL: 0.42). OPG correlated with BFR (r=0.473, p<0.01) and adjusted apposition rate (r=0.42, p<0.01), while inversely correlated with osteoid maturation time (OMT) (r=-0.34, p<0.03) and mineralization lag time (r=-0.45, p<0.01). RANKL/OPG ratio was negatively correlated with mineral apposition rate (r=-0.35, p<0.03) and positively with OMT (r=0.31, p<0.05). PTH was correlated with BFR (r=0.40, p<0.01) and resorption area (r=0, 54, p<0.01), but not with any mineralization markers. There were no correlations between PTH and OPG or RANKL. Conclusion: OPG, in contrast to RANKL, exerts a dual effect on the skeleton by promoting mineralization and increasing BFR. These osteogenic markers might be of benefit in characterizing the turnover, mineralization and volume of the skeletal lesions of secondary HPT as recently recommended by KDIGO. "Sevcan Bakkaloglu was supported by TÜBITAK (Scientific and Technological Research Council of Turkey). This study was supported by USPHS grants DK-35423, DK-67563 and MO1-RR00865. " PTH values are widely used to guide therapy for renal osteodystrophy in patients treated with maintenance dialysis yet target values are based on cross-sectional studies and discrepancies between bone formation rates (BFR) and PTH have been described during intermittent calcitriol Rx. Thus, we evaluated the relationship between serum biochemical parameters and bone turnover during treatment with intermittent vitamin D sterols. 60 patients aged 13±1 yrs with biochemical and bone biopsy (BBx) proven 2 nd HPT received 8 months of vitamin D (1, 25D 3 or 1D 2 ) given in twice weekly oral dosing and phosphate binders. Dose of vitamin D was titrated upwards monthly to maintain 1 st PTH-IMA(Nichols R ) levels between 300-400 pg/ml. BBx was then repeated. S-Ca, P, Alk P-tase and PTH by 1 st and 2 nd PTH-IMAs were obtained monthly throughout therapy. Baseline values were: P: 6.2±0.1 mg/dl, Ca: 9.2±0.1 mg/dl, Alk P-tase: 397±36 IU/L, 1 st PTH-IMA 940±55 pg/ml, 2 nd PTH-IMA: 510±41 pg/ml. Final values were: P: 5.5±0.1mg/dl, Ca: 9.4±0.1 mg/dl, Alk P-tase: 324±35 IU/L, 1 st PTH-IMA: 565±43 pg/ml, and 2 nd PTH-IMA: 280±27. Bone formation rate (BFR/BS) decreased from 114±8 to 55±5 um 2 /mm 2 /d (nl: 10-73.4); 72% achieved normal bone turnover. 2 nd PTH-IMA values were 40-50% lower than 1 st PTH-IMA levels; there was no difference in predictive capability of the two assays. Patients achieving normal BFR/BS had 1 st PTH-IMA values of 508±44 pg/ml. The sensitivity, specificity and PPV of a 1 st PTH-IMA range of 300-600 pg/ml for normal BFR/BS were 70% (95% CI: 50-86%), 60% (26-88%), and 83% (61-95%) respectively. During therapy with intermittent vitamin D sterols, maintaining PTH levels higher than currently recommended results in normal BFR/BS and prevents adynamic bone.

Maternal diabetes will induce abroad array of congenital malformation. Consistently with these hypotheses, we observed the defects of renal development of diabetic pregnancy from late phase of embryogenesis to postnatal period in animal model (C57BL/6J mice). Histological analysis of phenotypes revealed decreased glomerular numbers, glomerular hypertrophy and hypercellularity, as well as renal tubular detachment in sequential late phase of kidney development in the offspring of diabetic female mice. TUNEL assay showed signficinatly increased cell apoptosis in fetal kidneys of hyperglycemic group. RT-PCR and FISH study of kidneys of fetal and newborn mice revealed that Gdnf and early growth response alpha (Egr-α) are two of crucial genes inhibited in hyperglycemic ambience. In human, we presumed that children of gestational hyperglycemic mothers have the same defects of renal development as our animal model similarly, thus we measured and compared echogram of kidney/liver echoenic ratio in 76 children born to gestational hyperglycemic mothers and 240 health children. Interestingly, our human ultrasonic study indicated that after age of 6 months, the diabetic children had increased echogenic ratio of kidney/liver than the healthy age matched children (p<0.01). We also found that 26.3% of diabetic children had nonobstructive hydronephrosis. This simple sonographic procedure may provide a permissive was for clinicians to obtain the basis of long-lasting follow-up of these high-risk children as early as possible. Keywords: diabetic embryopathy, renal development, glial cell line-derived neurotrophic factor, early growth response alpha, renal sonogram. Genetic inactivation of Spry 1 in mice results in increased number of UB branches and expanded GDNF, c-Ret and Wnt-11 expression domains (Basson et al., Dev. Cell, 2005) , indicating that Spry1 is a negative regulator of the GDNF-Ret-Wnt11 pathway. ANG Ii induced UB branching morphogenesis, partly via stimulation of EGFR tyrosine kinase activity (Yosypiv et al. JASN, 2006) . We tested the hypothesis that ANG II stimulates the GDNF-Ret pathway via repression of Spry1. CD1 mice metanephroi were dissected on embryonic (E) day E12.5, grown on filters in the presence or absence of ANG II (10 -5 M, n=5/group) for 24 hours and subjected to whole-mount ISH with digoexigenin-labelled Spry1, c-Ret, Wnt-11 and GDNF cRNA probes. Spry1 mRNA was expressed in UB branches and in condensing mesenchyme. c-Ret and Wnt-11 were expressed in UB tips, and GDNF-in the metanephron mesenchyme. ANG II downregulated Spry1 expression in the UB. In contrast, c-Ret and Wnt-11 were induced by ANG II in the UB tip cells. GDNF expression in the mesenchyme was also upregulated by ANG II. In addition, ANG II stimulated UB tip cell proliferation, as determined by in vivo BrdU in corporation (28.5±2.4 vs.9.7±1.2; p<0.001) compared to control. These findings suggest a model in which ANG II-mediated inhibition of Spry1 gene expression releases. Ret tyrosine kinase activity leading to upregulation of c-Ret and its downstream target gene, Wnt-11. Enhanced Wnt-11 expression, in turn, induces GDNF in the adjacent mesenchyme. This causes focal bursts of UB tip cell proliferation and branching. These results support the hypothesis that abnormal collecting system development in angiotensinogen, renin, ACE or AT1-deficient mice is at least partly due to aberrant regulation of the UB branching morphogenesis program. Objectives of Study: Nephrogenesis requires a fine balance of many factors that can be disturbed by intrauterine growth restriction (IUGR), leading to a low nephron endowment. Our previous studies have shown that offspring born to mothers supplied low protein diets during pregnancy have fewer glomeruli than normal at birth in SD rats. The aim of this study was to identify the possible pathogenesis of abnormal nephrogenesis and decreased glomerular number in IUGR by comparative proteomic approach. Methods: IUGR was induced in SD rats by isocaloric protein restriction in pregnant dams. Kidney proteins were obtained from 6 neonatal normal rats (control group) and 8 IUGR rats (IUGR group) respectively. A series methods including 2-DE, silver staining, mass spectrometry and database searching were used. The 2-DE test was repeated three times in each group. Results: After silver staining, the 2-DE image analysis detected average 730±58 spots in IUGR group and 711±73 spots in control group. The average matched rate was 86% and 81% respectively. The differential proteomic expression analysis found eleven protein spots were expressed only in IUGR group and one in control group. Seven protein spots were up-regulated more than 5 folds and two down-regulated more than 5 folds in IUGR group compared with those in control group. These 21 protein spots were preliminarily identified, which were structural constituents of cytoskeleton including vimentin, cytokeratin 10, perlecan and b-actin, transcriptional factors including splicing factor, Rho GDP dissociation inhibitor alpha and cell division proteinkinase 2, enzymes including retinal dehydrogenase1, transketolase and so on. Conclusions: Data from this study may provide, at least partly, valuable experimental evidence of proteins involved in the pathogenesis of abnormal nephrogenesis and decreased glomerular number in IUGR. The aim of the study is to describe the natural history of TCF2/Hepatocyte nuclear factor-1 beta linked disease in children. Prenatal and postnatal renal evolution and extrarenal manifestations of 33 patients were reported. Thirty one had prenatal diagnosis of developmental nephropathy: bilateral foetal hyperechogenic kidneys or a hyperechogenic kidney with a controlateral multicystic dysplastic kidney. 64% had cysts. The mean prenatal renal length was normal (0, 29 SD) . Intrauterine growth was normal with median birth weight of 3.1 kg (range 1.6-3.6) and 30% were small for gestational age. After a mean follow-up of 79 months, the renal growth was impaired with a mean renal size of -0.78 SD. Patients with a solitary functioning kidney showed no compensatory hypertrophy. Thirty one patients developed bilateral nephropathy and 2 isolated unilateral multicystic kidney. Twenty eight patients had cysts, mainly cortical bilateral microcysts. The mean GFR was 73.19±30.43 ml/min/SC. Sixteen patients had stage 1 chronic kidney disease (CKD), four were classified as stage 2, eleven as stage 3 or 4 CKD and two were diagnosed with end stage renal failure. Annual decline of the glomerular filtration rate was 3.4 ml/min. Extrarenal manifestations included 3 patients with diabetes, one with exocrine pancreatic insufficiency, one with pancreatic hypoplasia without clinical symptoms and 4 with cholestasis. We found a complete heterozygous deletion of the TCF2 gene in 20 patients and nine different point mutations. Three patients had the G76C mutation, 2 with unilateral MCDK and 1 with bilateral severe hypoplasia leading to early renal dysfunction. TCF2 gene anomalies are associated with low renal function decline but in some patients end stage renal failure appeared early in life. Long term follow-up is needed to determine the incidence of extrarenal symptoms, particularly diabetes.

Objectives: Although it has been observed more than one hundred years ago that the urinary tract is very resistant to infection, its antimicrobial mechanisms have not yet been systematically characterized. We sought to elucidate the expression and relevance of the antimicrobial peptide cathelicidin in this area. Methods: In order to investigate the expression of cathelicidin in health, urine samples from healthy children, pieces of healthy renal tissue, and cell cultures were analyzed. To evaluate the expression of cathelicidin during infection, urine samples from children with urinary tract infection, a mouse model of ascendant pyelonephritis and cell culture experiments were employed. The relevance of cathelicidin production was tested by bacterial challenge of cathelicidin-deficient and neutropenic mice. In addition, we studied the in vitro effects of cathelicidin on the growth and multicellular behavior of bacteria as well as we tested sensitivity of clinical E. coli strains to the peptide. Results: Cathelicidin is expressed by epithelial cells of healthy urinary tract and excreted into urine in low concentrations. During urinary tract infection, the secretion of cathelicidin by epithelial cells significantly increases within minutes. Invading neutrophils are the source of the second wave of cathelicidin. Epithelial cathelicidin protects the urinary tract against bacterial infection while neutrophil-derived cathelicidin influences the severity of infection. Cathelicidin displays multiple effects on bacteria. Low concentrations of cathelicidin inhibit multicellular behavior, e. g. biofilm formation of E. coli, and high peptide concentrations kill bacteria. Bacteria resistant to cathelicidin have an increased ability to invade the urinary tract. Conclusion: The antimicrobial peptide cathelicidin is a key factor of the mucosal immunity of the urinary tract.

The predictive value of procalcitonine (PCT) plasma level for renal scarring after an acute pyelonephritis (APN) is still debated. During APN, the bacterial Lipopolysaccharide of the membranes induce the release of TNF, IL1 and IL6. These cytokines lead to inflammation syndrome and fibrosis sequellae resulting from cell apoptosis induced by nitric oxide (NO) release that is catalysed by NO-synthase. The aim of this work was to clarify the physiological role of PCT in renal parenchyma apoptosis and fibrosis caused by APN. We conducted a prospective study in children with a first APN episode (fever>38.5C°, CRP>20 mg/l, monomicrobial urine positive culture>10.5 fcu/ml). We excluded patients with any concomitant infection, renal dysplasia or obstructive uropathy or grade 4-5 VUR 133 children were enrolled (age 37.2 m, median 17 m). On admission, PCT, CRP and phospholipase A2 (Pla2) were quantified in serum. Scintigraphy with 99m Tc-DMSA was performed on day 4 and 9 months later in case of initial abnormalities. Fisher's test was performed and statistical significance was defined as p<0.05. Results: on day 4, 107 (79%) presented renal parenchyma alterations, at 9 m 57 underwent control scan and 17 (28%) had renal scars. Pla2 and PCT levels were correlated with early DMSA lesion but not with renal scars at 9m. Paradoxically, initial PCT level was significantly lower in the presence of renal scars (4.19 vs 7.59 ng/ml, p<0.01). Significant PCT increase was observed in favourable progress (recovery 7.55 vs aggravation 3.34 ng/ml, p<0.01) and no difference between recovery and improvement evolution. These results suggest the protective effect of PCT against apoptosis resulting from down-regulation of nitric oxide release; so high PCT values could be interpreted with caution in APN.

Acute pyelonephritis (APN) may lead to renal scarring with later risk of hypertension and renal insufficiency. The aims of this study were to analyse prospectively renal scars progression with time and their impact on renal growth. Methods: 52 patients (pts), aged from 0 to 18 years who presented scars on DMSA at 6 months after APN were included. In these children a second DMSA was done after 3 years. Evolution of scars was analyzed following pre-established criteria independently by 3 observers. Scar progression was classified as follows: 0=no change, 1=partial improvement, 3=total resolution. In addition a renal ultrasound was repeated to assess kidney growth using Z-score. Results: 104 renal units (52 pts: 32 F, 22 M) were studied. The incidence of vesicoureteral reflux (VUR) was 34.6% (18/52). Per renal units, VUR were observed in 27/104 (26%); (51% VUR Grade (G) I, II and 49% G III, IV). There were 91 scars observed 6 month after APN which evolution over 3 years was as follow: 0=26% (24/91), 1=65% (59/91) and 2=9% (8/91). Incidence of VUR was higher in children presenting 3 scars; 5/7 (71%) against 12/45 (26%) in those with 1 or 2 scars. To identify factors interfering with renal growth, we analyzed potential confounding variables using robust linear regression. Z-score was worsened with increased number of scars observed at 6 month after APN p<0.001) and improved with disappearance of VUR (0.89 CI 0.001-1.7; p<0.05). Conclusion: Between 6 month and three years after APN, 82% of scars improved. In our population, the number of scars secondary to PNA was the most important factor affecting renal growth. The second prognosis criterion was the correction of VUR. Prevention of PNA and rapid treatment to avoid kidney scars seems to be the essential aim to preserve optimal kidney growth.

V. Smolkin 1, 2 , R. Halevy 1, 2 , W. Sakran 1, 4 , Y. Kennes 3 , A. Koren 1, 4 1 Ha'Emek Medical Center, Pediatric B, Afula, Israel 2 Ha'Emek Medical Center, Pediatric Nephrology Unit, Afula, Israel 3 Ha'Emek Medical Center, Bacteriology and Microbiology Laboratory, Afula, Israel 4 The Ruth and Baruch Rappaport School of Medicine, Haifa, Israel Febrile urinary tract infection (UTI) is a relatively common infection disease in childhood. Children consider at risk for UTI commonly receive prophylactic antibiotics to prevent recurrence of this urinary tract disease because of the risk of kidney scarring, which may lead to complications such as hypertension or end-stage renal disease. Compliance with antibiotic prophylaxis after UTI was assessed in 69 children, using a parent questionnaire and a urine test for antibacterial substances. Thirty six children (1 st group) received prophylactic treatment during the period of 4 months (range 3-7months) and the other 34 patients (2 nd group) received antibiotic prophylaxis for a longer duration (12 months, range 11-16 months). In the first group of patients, 35 (98%) of parents reported giving the antibiotics every day in comparison with 30 (88%) in the 2 nd group. Twenty nine (81%) of urine tests were positive for antibacterial substances in the 1 st group but only 16 (47%) in the second group. In the 1 st group of patients the difference in recurrent infection between regular takers and non-takers was statistically highly significant. No significant difference was found in recurrent UTI rate in takers and non-takers in the 2 nd group. Failure to understand the reason for prophylaxis and forgetfulness was found to be a main reason for non-compliance. Imaging studies evaluating the kidneys and urinary tract are performed routinely after a febrile UTI. Evidence of their value in changing management or affecting long term outcome is limited. As part of a multicentre, RCT (IRIS 1) evaluating different antibiotic regimes in the treatment of first febrile urinary tract infections, we undertook as a secondary objective, an evaluation of the diagnostic protocol. The imaging modalities (ultrasound, DMSA scintigraphy within 10 days and voiding cystogram within 1-2 months) were assessed for their ability to predict long term parenchymal damage. 337 children of 2 years of age or less at the time of investigation and who had normal renal function and antenatal ultrasound, were considered suitable for analysis of the diagnostic course. US was performed in 336 children with 288 (86%) normal, minor changes were noted in the remainder, apart from 1 case requiring a change in management in the form of a pyeloplasty for pelvi-ureteric obstruction. The cystourethrogram was performed in 323 of the children with 65 (20%) demonstrating VUR. The cystogram was a poor predictor of long term damage, being positive for reflux in only 17 of the 39 children who subsequently developed scarring. An acute DMSA scan performed in all children, exhibited findings consistent with acute pyelonephritis in 212 (63%). A repeat DMSA scan at 12 months in those with evidence of acute pyelonephritis demonstrated a scarring rate of 24%. The data did not demonstrate the clinical efficacy of routinely performing scintigraphy in the acute phase or a cystourethrogram. Our recommendations for a reasonable diagnostic work up in small children with their first episode of UTI are 1) performance of a scintigram 6 months following the acute infective episode, and 2) close surveillance to identify eventual recidivists.

Introduction: Focal Segmental Glomerulosclerosis (FSGS) has a high recurrence rate after Renal Transplantation (RTx). Recurrence can lead to Tx Loss. Disease recurrence (DR) seems to be influenced by genetic background. Methods: 77 patients with childhood onset of biopsy proven FSGS who were transplanted were evaluated. Genetic investigations of the NPHS2 gene were done in 46 patients (59.7%). Results: Mean age at diagnosis was 6.06 years. First renal transplantation was performed at age of 12.3 years.18 patients received a living related (LRD), 55 a deceased donor (DD) Graft. 4 Patients data under investigation. 31 P (40.3%) recurred after a mean time of 6, 3 years, 5 P with LRD (27.8%) , 25 P with a DD (45.5%). 23 patients (29.9%) lost their graft after 6, 8 years, 15 patients due to recurrence. A second RTx was performed in 16 patients, 11 with DD, 2 with LRD, 3 Patients data under investigation, with 71% DR. A third transplantation was performed in 7 patients and a fourth in one patient. Screening for NPHS2 mutations revealed 10 patients with mutation in the NPHS2 gene, 9 homozygot, 1 heterozygot. All patients with a homozygote NPHS2 mutation did not recur and only the one patient with a heterozygous mutation (1/10) recurred compared to 17/36 without a mutation (p<0.05). Conclusion: Living related transplantation was advantageous to decreased donor transplantation. Patients with NPHS2 mutations had a lower risk of recurrence after transplantation compared to patients without mutations. Patients with FSGS should be screened for NPHS2 mutations.

Objective: Prospective EBV surveillance post tansplantation reduces incidence of acute rejection and risks of post transplant lymphoproliferative disorders (PTLD). Methods: Prospective screening of EBV by polymerase chain reaction (PCR) and serology in all patients transplanted between 2003 -2006 . Results: 27 patients transplanted between May 2003 and September 2006 . 22 were cadaveric and 5 live-related transplants. Recepient EBV serology status was known but not on donors. Basiliximab was used for induction and maintenance comprised of Tacrolimus/azathioprine (AZA) until 2004 and mycophenolate (MMF)/tacrolimus from 2004. All received corticosteroids. 17 had MMF/Tacrolimus, 10 AZA/Tacrolimus. EBV screened within first week post transplant, weekly for a month, monthly for 6 months. When EBV PCR LV >5.0, MMF/AZA was withdrawn, tacrolimus levels kept between 6-8 ng/ml. PCR/ serology is checked 2 weekly for 3 months, monthly for 6, until LV falls <5.0 and VCA IgG becomes positive. The MMF/AZA is reintroduced. Patients with EBV PCR LV <5.0 are kept on full immunosuppression while viral load and VCA IgG monitored. 17 EBV viraemia detected following prospective screening.1 was re-activation. 9 were symptomatic. Onset varied 1 to 21.7 months post transplant (mean 4.3 months). 10 were on MMF/Tacrolimus 7 received AZA/tacrolimus. 12 had PCR LV>5.0 consequently maintained on Tacrolimus an alternate day steroids for period of time. CMV patient and donor status was known and antiviral prophylaxis given to nonimmune. The use of antivirals made no impact on viral load. Conclusion: No patient experienced acute rejection or PTLD despite modification of therapy with our prospective screening programme. Antivirals have no role in protecting or reducing viral load in already infected patients. Graft attrition rate is highest in the first three months after renal transplantation. We analysed data in a recent cohort from all Dutch centres for pediatric renal transplantation to determine incidence and causes of such early graft failure. Methods: Data from all pediatric renal transplants performed between 01-01-98 and 01-01-06 were analysed retrospectively. A common immunosuppressive protocol was used in all centres. Thrombosis prophylaxis was given according to centre policy. Early failure was determined as graft failure within 3 months after transplantation. Prevalence of possible risk factors of graft failure identified by literature search were extracted from patient charts. Data were analysed with univariate and multivariate logistic regression. Results: The cohort consisted of 228 transplants. Age of the recipients was 3-18 yrs (mean 10.9). There were 19 early graft failures (8.2%). Major causes of graft failure were thrombosis (5.3%) and ARE(1.8%). Univariate analysis identified an association of early failure with complications during surgery (OR 10.0, p=0.00), cold ischemia time (OR 1.1, p=0.026), side of graft donation (OR 2.8, p=0.046) and diuresis in the first hour after transplantation (OR 0.3, p=0.026). Multivariate regression analysis showed that complications during surgery were associated with the risk of early failure (OR 6.4, p=0.002), as were side of graft donation (OR 5.7, p=0.015) and diuresis in the first hour after transplantation (OR 0.3, p=0.038) . Only the occurrence of complications during surgery was significantly associated with early graft failure due to thrombosis (OR 13.6, p=0.006). Conclusion: Thrombosis is the major cause of early graft failure after renal transplantation in Dutch children, especially after surgical complications. Prospective studies are needed to determine whether early failure can be decreased by more rigorous prophylaxis. Background: Interleukin (IL)-1 is a major contributor to inflammation and cell death during ischemia-reperfusion (IR) injury and its deleterious effects are mediated mainly by nuclear factor-κB (NF-κB) activation. Receptor binding and signalling of IL-1 can be blocked by the IL-1 receptor antagonist (IL-1ra). The aim of our study was to characterize the effects of IL-1ra administration on inflammation, apoptosis and infiltration in renal IR injury. Methods: Renal ischemia was induced in Lewis rats (n=7/group) by clamping of the left renal artery for 45 min followed by reperfusion of 24 h or five days respectively, when kidney were removed for histological and molecular analysis. Results: Treatment with IL-1ra ameliorated ischemic renal tissue injury and inflammatory infiltration. Futhermore, the number of apoptotic tubular cells was lower in IL-1ra treated animals 24 h after ischemia, which was paralleled by a Bax/Bcl-2 mRNA ratio towards anti-apoptotic effect. IL-1ra reduced the expression of monocyte chemoattractant protein-1 (MCP-1) mRNA 24 h and 5 days and that of intracellular adhesion molecule-1 (ICAM-1) expression 24 h after reperfusion in the kidney. Conclusions: Our results indicate that IL-1ra treatment ameliorates renal IR injury and this protective effect might be mediated by reduced induction of NF-κB mediated MCP-1, ICAM-1 and the decreased ratio between Bax and Bcl-2 mRNA expression.

K. Satomura, Y. Santo Osaka Medical Center for Maternal and Child Health, Pediatric Nephrology and Metabolism, Izumi, Japan Many studies have reported that angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) show renoprotective effects in adult patients with acquired renal diseases. However, these effects have not been studied in children with renal hypoplasia or dysplasia (RHD). In this study, we explored the renoprotective effects of these drugs in children with RHD. Patients and Methods: Participants of the study were patients with RHD aged less than 15 years. A follow-up for more than one year was conducted in our outpatient clinic. The patients had chronic renal failure, and had not received ACEI or ARB in the past. The change of glomerular filtration rate (GFR) per year, urinary protein/creatinine (uP/Cr) ratio, serum potassium levels, and blood pressure before the treatment with trandolapril or candesartan were compared with those of one year after the treatment. The estimated GFR was calculated by the Schwartz formula. Wilcoxon rank sum test was applied to evaluate the statistical significance. Results: Eleven patients were eligible for this study. The mean age of the patients was 8.4±2.6 years and the estimated GFR was 57.3±9.0 ml/min/1.73 m 2 when trandolapril or candesartan was administered. The change in the estimated GFR for a year significantly improved after the treatment with trandolapril or candesartan compared with the pre-treatment period (-6.1±5.4 vs. 1.9±5.9 ml/min/1.73 m 2 /year, p=0.003). The uP/Cr ratio significantly decreased at one year after the treatment compared with that before the treatment (0.67±0.62 vs. 0.49±0.53, p=0.041). The blood pressure and serum potassium level showed no significant changes. Conclusion: These data suggest that treatment with ACEl or ARB has beneficial effects on the renal function in children with mild to moderate renal failure due to RHD. Objective of the study: Postischaemic ARF is influenced by sex hormones. Dehydroepiandrosterone (DHEA) pretreatment diminishes postischemic injury. Previously we demonstrated that after renal ischaemia-reperfusion (I-R) injury the expression and activity of Na, K-ATPase (NKA) is impaired in male rats. Here we tested the impact of DHEA on postischaemic survival, renal damage, mRNA and protein expression of NKA. Methods: Left renal pedicles of DHEA (4.0 mg/kg/day) and propylene glycol, as vehicle (PG) treated male rats (G DHEA and G PG , respectively) were clamped for 55 min followed by 2 (T 2 ) and 24 (T 24 ) hours of reperfusion. Survival rate, histological damage, serum creatinine (CN) and urea nitrogen (BUN) were investigated. The mRNA expression and protein level of NKA α1 and β1 subunit were also determined. Sham operated animals served as control. Results: DHEA treatment was associated with better postischemic survival (p<0.05 G DHEA vs. G PG ). Postischaemic CN and BUN were higher and renal histology showed more rapid progression vs. controls, however there was no difference between G DHEA and G PG groups. mRNA expression of NKA α1 subunit was higher in G DHEA vs. G PG at every time points, however it was decreased in I-R groups vs. controls (p<0.05). Similar changes were observed in NKA α1 protein level (p<0.05, G DHEA vs. G PG in controls, T 2 , T 24 ). mRNA and protein expression of α1 subunit were different only at T 24 (p<0.05, G DHEA vs. G PG ). Conclusions: Our study indicates that NKA is more protected from the detrimental effects of I-R injury in DHEA treated animals, which might be a contributing factor of improved postischaemic renal function and could help to preserve cell and organ homeostasis even in male animals. The work was supported by OTKA F048842-T37578, Bolyai and Semmelweis grants. Objective of study: Recently BNP has been identified as a useful cardiac marker for risk stratification in adults. Whether BNP has a similar diagnostic potential in pediatric population with CKD has to be established. The aim of the study was to assess the value of BNP to predict the cardiac dysfunction in children with CKD. Methods: To test this suggestion, the relationship between plasma concentrations of BNP, echocardiographic parameters and cardiovascular risk factors (lipid profile, hypertension, secondary hyperparathyreoidism) has been evaluated. A cohort group consisted of 46 children and young adults (35 pts mean age x=16.12±5.14 years; 11 controls mean age x=14.73±5.04years). Out of 35 studied pts 24 children were with CKD stage 4 and 5 K/DOQI (12 pts CKD stage 4; 12 dialyzed pts) and 11 transplanted subjects with stable graft function (GFR=1.17±0.7 ml/s/1.73 m 2 ). Results: No association was found between BNP and GFR and/or s-creat (p=0.12; p=0.1; p=0.44). The highest BNP plasma levels have been found in dialyzed children (620.77 pg/ml; resp. 75.98 pg/ml in TX; resp. 51, 85 pg/ml in CKD stage 4 group) as compared to controls (35, 25 pg/ml p<0,001). BNP was independently related to left ventricular mass (r=0.84; p<0.001) as well as to ejection fraction (r=-0.6; p<0.001) and preload (r=0.78; p<0.001). Significant correlation between BNP and hypertension (r=0.608; p<0.001) has been observed. More over, BNP correlated with iPTH (r=0.37; p<0, 05) and diastolic dysfunction (r=0.61; p<0, 001). Plasma BNP concentrations did not significantly differ before/after dialysis procedure (p=0.07). Conclusions: BNP is a sensitive marker for cardiac dysfunction in CKD children. However, prospective studies in larger group of pts are needed to confirm our preliminary data. We have reviewed the data of 20 patients with Nephropathic Cystinosis (NC) followed in our department since 1987. Overall, 2 patients have died during the follow-up period. The mean follow-up was 17,6±6,7 yrs (range 6, 8) . 13/20 patients have initiated dialysis and 10/20 received a cadaveric renal transplant. Univariate analysis showed that the time to reach a serum creatinine value of 2 mg/dl was significantly associated with the patient's age at the last follow-up (O. R. 1, 3/yr; p<0.001), the age at the beginning of cysteamine (MEA) treatment (O. R. 1, 3/yr; p=0.006), the dose of MEA (O. R. 0, 99/g, p=0.035) and the use of ACE-inhibitors (O. R. 0, 15; p=0.014). By multivariate analysis, only the period of treatment (OR 1, 24, p=0.037) and therapy with ACE-inhibitors (OR 0, 16, p=0.041) were significantly associated with better outcome. Similar results were obtained when assessing the time to dialysis. There was a significant correlation between the dose of MEA with intra-leucocytic cystine levels (ILC). By univariate analysis, the dose of MEA expressed in mg/m 2 correlated more with the outcome then the dose expressed in mg/kg. Statural growth was significantly associated by multiple correlation analysis only with Growth Hormone (GH) treatment (p<0.05). Altogether, these results indicate that the renal prognosis of NC has been improving over the past two decades. This improvement may not be solely attributable to the introduction of MEA for the treatment of NC. Our data suggest that the overall management of these patients has improved, including more efficient symptomatic treatment of the Fanconi syndrome and the use of medications such as ACE inhibitors and GH. Background: The Chronic Kidney Disease in Children (CKiD) cohort study, targeted to enroll 540 children aged 1-16 yrs with chronic kidney disease (CKD) by estimated GFR (eGFR Schwartz) of 30-90 ml/min/1.73 m 2 aims to assess risk factors for kidney disease progression in children. Objective: To describe the characteristics of the CKiD cohort at study entry. Design/methods: At the CKiD baseline visit, GFR is measured by plasma disappearance of iohexol. Children undergo physical exam, standardized BP measurements, blood and urine testing and parent and child interview. Results: As of 01/16/07, 335 children had completed the baseline visit, median age 11.1 yrs, 71% Caucasian, 16% African American, 62% male and 15% Hispanic ethnicity. Median age-adjusted height and weight percentiles were 23% and 42%, respectively. Underlying cause of CKD was urologic, cystic or hereditary in 68%, 21% had acquired glomerular disease. Median eGFR at study entry was 54.6 ml/min/1.73 m 2 , 40% higher than the median iohexol-based GFR 38.5 ml/min/1.73 m 2 . 48% of participants reported a history of hypertension, 35% anemia, 11% seizures, and 7% depression. Symptoms of headache, nausea, loss of appetite and weakness steadily increased in prevalence with lower GFR. Assessment of family history in parents and grandparents revealed: high blood pressure 81%, high cholesterol 66%, kidney disease 29%, dialysis 12%, and kidney transplant 6%. Conclusions: Children with Stage III CKD have significant height deficits, hypertension, anemia, and seizure disorders. Cross-sectionally, increasing non-specific symptoms are associated with lower GFR. Collection of plasma, serum and genetic material will facilitate understanding of novel risk factors and biologic mechanisms underlying kidney disease progression and associated morbidities. Aim: Increased glomerular filtration rate (GFR) has been implicated in the development of diabetic nephropathy. Large normal interindividual variations of GFR hamper the diagnosis of renal hemodynamic alterations. We examined renal functional reserve (RFR) in children with insulindependent diabetes mellitus (IDDM) to assess if hyperfiltration occurs. Methods: The renal hemodynamic response following dopamine infusion was examined in 51 IDDM children (7.7±3.6 y) with a mean duration of diabetes of 6.2 years and compared to 34 controls. Results: Mean baseline GFR in diabetic children did not differ from control population (130.7±22.96 vs. 124.8±25 ml/min/1.73 m 2 ), whereas renal plasma flow was significantly lower (463.7±103.9 vs. 587.2±105ml/min/1.73 m 2 , p<0.001) and filtration fraction was increased (29±8 vs. 21±2%, p<0.001), compared to controls. The mean RFR was lower (p<0.001) than in control subjects (-0, 77±23 vs. 21±8 ml/min/1.73 m 2 ). Conclusion: The observation that RFR is reduced or absent suggests that all children are in a state of glomerular hyperfiltration with increased intraglomerular pressure regardless of the baseline normal values of GFR. While measurements of RFR may be helpful in diagnosing the presence of hemodynamic changes, the relevance to development of diabetic nephropathy remains unknown. Only 30-40% develops diabetic nephropathy, suggesting that glomerular hyperfiltration is only a concomitant risk factor. LP diet induces ischemic renal injury involving epithelial cells from OSOM. Here, we tested whether HSP70 would stabilize renal Na+K+ATPase attachment to the cytoeskeleton during recovery from LP. After weaning, rats (n=8), were fed for 14 days with a LP diet (8%), then were recovered by means of a normal protein diet (24%RP) each group had an age-matched control group (24%, NP). Tissues from cortex and OSOM were homogeneized in buffer plus 0.1% Triton X-100. Protein levels were measured by Western blot. In vitro coincubation of solublen on cytoeskeletal and insoluble cytoskeletal-associated fractions in the presence or absence of anti-HSP70 antibody was performed. Interaction between proteins was determined by coimmunoprecipitation. Increased Na+K+ATPase dissociation was shown in soluble fraction from OSOM as a result of LP diet vs. NP (196.5±1.1 vs. 151±1.3, p<0.05). Meanwhile, decreased HSP70 levels in the same fraction was shown (LP: 179.3±10.5 vs. NP 224.7±1.85, p<0.05). Translocation of HSP70 to the cytoeskeletal injured fraction associated with stabilization of Na+K+ATPase was shown in OSOM from LP, after in vitro coincubation of the cytoskeletal fraction of LP and non cytoskeletal fraction of RP. These effects were abolished by the addition of anti-HSP70 antibody. Coimmunoprecipitation showed that the amount of HSP70 coprecipitating with Na+K+ATPase increased in LP OSOM, in RP results were similar to control. In cortex, absence of significant differences was shown in the Na+K+ATPase and HSP70 expression at in vivo and in vitro experiments among groups. In LP and RP cortex tissues, interaction of both proteins was similar to control. Our results allow us to suggest that HSP70 has a critical protective role in the integrity of the cytoskeletal anchorage of Na+K+ATPase during recovery from ischemic LP injury in OSOM. Tubular reabsorption of Mg +2 occurs predominantly by paracellular flux in the thick ascending limb of the loop of Henle. It is mediated by the, tight junction, Mg +2 channel protein, paracellin-1, which is encoded by the gene PCLN-1. Cyclosporin A (CsA), a widely used immunomodulatory drug, decreases tubular Mg +2 reabsorption leading to urinary Mg +2 wasting and hypomagnesemia. The exact molecular mechanisms of this modulation are unknown. In this study we examined the effect of CsA on the paracellin-1 gene in renal cell lines and mouse kidney. The effect of CsA on the PCLN-1 gene promoter was examined. A plasmid, containing the human PCLN-1 (hPCLN-1) promoter (2.5kb) upstream to a luciferase reporter gene, was transfected into opossum kidney (OK) and human embryonic kidney (HEK293) cells prior to exposure to 5 micrograms/ml CsA for 24 hours. Mice received CsA (15 mg/kg/day) for up to 5 days. At 24 h intervals blood/urine Mg +2 and Ca +2 levels were determined and kidneys harvested for paracellin-1 mRNA quantitation (real-timePCR) as well as protein quantification (Western blot) and visualization (immunofluorescence). CsA decreased hPCLN-1 promoter activity by 25%-50% in transfected OK and HEK293 cells, compared to control cells. CsA-treated animals displayed hypomagnesemia with increasing urine Mg +2 and Ca +2 levels paralleled by a 20-30% decrease in PCLN-1 mRNA after 3 and 5 days of CsA exposure. A similar effect on paracellin-1 protein expression inthe renal tubule was evident in response to CsA treatment. CsA may influence paracellin-1-mediated Mg +2 transport at the transcriptional level. Involvement of the calcineurin-dependent TonEBP pathway or the calcineurin-independent MAP kinase pathway in this response is subject to future research. This effect of CsA on the paracellin-1 gene may play a role in the renal magnesium wasting and hypomagnesemia induced by CsA. It is well established that proteinuria induces tubular injury, which is closely associated with progressive decline of renal function. Megalin has an important physiological role in the reabsorption of a variety of low molecular weight proteins along the proximal tubule. In this study, we examined whether megalin mediates tubular injury secondary to glomerular diseases. We utilized megalin knockout (KO) mice, in which 60% of proximal tubular cells have mosaic nullmutation in the megalin gene. To induce glomerular injury, these were mated with a transgenic line, NEP25, in which selective podocyte injury can be induced by injection of immunotoxin, LMB2. Megalin KO/NEP25 mice were injected with LMB2 (0.625 ng/g BW) and analyzed 2 weeks later. They showed moderate proteinuria (Upro/Cr=80, vs 12.5 before LMB2) and mild tubular injury, which were comparable to those observed in NEP25 mice with intact megalin gene injected with the same dose of LMB2. In the latter, megalin was still detectable in injured tubules. Within each megalin KO/NEP25 mouse, we compared megalin-intact (+) vs deficient (-) proximal tubular cells by immunostaining. The majority of megalin+ cells showed enhanced staining for albumin. In contrast, most megalin-cells were not stained for albumin. Aquaporin-1, which is highly expressed in normal proximal tubules, was diminished in 39.7% of megalin+ cells, whereas it was diminished in only 11.3% of megalin-cells. Some proximal tubular cells expressed MCP-1. In that, 69% of MCP-1 expressing cells were megalin+. The results suggested that megalin plays an important role in the reabsorption of massively filtered proteins in glomerular diseases, thereby contributing to proximal tubular cell injury. Objectives of study: The hallmark of nephropathic cystinosis is lysosomal cystine accumulation, primarily leading to Fanconi syndrome. Although all tissues haveelevated cystine levels, it is not known why the kidney is first affected. It is postulated that decreased ATP production in cystinosis results in defective proximal tubular reabsorption, a process driven by Na, K-ATPase. To study this hypothesis, we have monitored ATP levels and viability in conditionally immortalized proximal tubular cells (PTC) of cystinosis and healthy controls. Methods: Urinary sediment of cystinotic patients and healthy controls was suspended ins supplemented culture medium. Primary cultures were transfected with SV40 ts A58 T antigen allowing proliferation at 33°C and maturation at 37°C. To confirm the proximal origin of the cells 1) expression of aquaporin-1 (AQP1) and dipeptidyl-peptidase IV (dpp-IV) was demonstrated using immunoblot technique and 2) morphology was determined using EM. PTC were matured at 37°C for 0-10 days, followed by cystine measurement using HPLC and ATP determination using luciferase assay. Results are expressed as nmol/mg protein.

Results: Colonies of cystinotic and control cell lines (n=2) with cobblestone morphology developed after 2 weeks and expressed AQP1 and dpp-IV, confirming their proximal origin. In cystinotic PTC, cystine levels increased from 2.0 at 33°C to 7.5 after 10 days at 37°C compared to 0.3 in controls. Intracellular ATP decreased in cystinotic PTC during 10 days from 8.8to 1.6, while ATP levels in controls remained stable (range 9.7-13.7). ATP levels inversely correlated with cystine accumulation in cystinotic PTC (r=-0.95, p=0.005). Conclusion: Decreased ATP levels in conditionally immortalized PTC during 10 days maturation suggest that alterations in ATP levels are involved in tubular dysfunction in cystinotic patients.

Aquaporin ( 13 AQPs have been identified to date. AQP1 conveys 50% of the peritoneal water transport in PD. Cell migration and angiogenesis are altered in AQP1 ko mice; erythrocyte pCO 2 depends on AQP1. Human peritoneal mesothelial cells (HPMC) from non-uremic patients and a human mesothelial cell line (Met-5a) were incubated with conventional (C-PDF), Icodextrin (ICO), bicarbonate (B-PDF) and lactate based double chamber PD solution (L-PDF). mRNA was measured by real time rtPCR, and protein by Western blot and immunocytochemistry. HPMC and Met-5a express AQP1, 3, 9 and 11. Incubation of Met-5a and HPMC with C-PDF, ICO and L-PDF did not change AQP1 and 3 expression compared to medium. In contrast, incubation with B-PDF increased AQP1 and 3 mRNA and protein in both HPMC (24 h AQP1 mRNA: 262±21, AQP3: 3226±634%) and Met-5A (AQP1: 1860±1180, AQP3: 2025±1624%). The effect on AQP1 was in part explained by differences in pH, the effect on AQP3 was largely independent of pH. Addition of 34 mmol/l of bicarbonate to L-PDF increased AQP1 and 3 mRNA (L-PDF+bic: AQP1: 983±110, AQP3: 326±26%). AQP9 expression was suppressed by all three PD fluids (B-PDF: 25±2.4, L-PDF: 16±9.6, C-PDF 75%: 26±11%), AQP11 was up regulated by B-PDF (377±37%). B-PDF improved HPMC migration. We for the first time demonstrate the expression of four different AQPs in peritoneal mesothelial cells. They are markedly regulated by PD-solutions. The upregulation of AQP1, 3, and 11 by bicarbonate based PDF may have important implications on long term peritoneal membrane function, wound healing and neoangiogenesis.

The Regulation of CX3CL1 (Fractalkine) by Thromboxane A2 In inflammation there is marked leukocyte infiltration into the damaged tissue. Chemokines recruit and direct leukocytes to the injured site. The chemokine CX3CL1 is up-regulated in renal inflammation such as glomerulonephritis and allograft rejection. Thromboxane A2 (TXA2), a potent vasoconstrictor in the kidney, is also pro-fibrotic. TXA2 is up-regulated early in inflammation and its effects are mediated by binding to the TP receptor. The aim of this study was to examine the effect of TXA2 on CX3CL1 expression. We previously showed that CX3CL1 recycles between the cell surface and an internal compartment. Cell surface CX3CL1 is cleaved by the enzyme, TACE, to yield the soluble species of the chemokine. We generated human ECV-304 cells stably expressing CX3CL1 and treated cells with a TP agonist. Levels of CX3CL1 were quantitated by Western blotting. CX3CL1 decreased by 30-60 min after TP stimulation, but recovered by 4h. Using flow cytometry, we found that cell surface levels of CX3CL1 decreased by 30 min, but began to recover before levels of total CX3CL1 were replenished. To verify if early recovery of CX3CL1 was due to redistribution from the internal to the plasma membrane compartment, we used fluorescence recovery after photobleaching (FRAP). After 60 min TP stimulation decreased endocytosis of CX3CL1 was seen. We postulated that loss of cell surface CX3CL1 is due to cleavage by TACE. Accordingly, a TACE inhibitor prevented early loss of CX3CL1 after TP stimulation. In summary, TXA2 induces rapid proteolytic shedding of cell surface CX3CL1 by TACE, but later increases expression of CX3CL1 at the cell surface by inhibiting internalization of the chemokine. This could release the soluble chemotactic protein from the cell adhesive transmembrane protein, promoting leukocyte recruitment initially, whilst promoting leukocyte adhesion later in the time course. The response to steroid therapy is used to characterize idiopathic nephritic syndrome (INS) as steroid sensitive (SSNS) or steroid resistant (SRNS). SSNS pathogenesis has been associated with activation of T-cells and SRNS has been associated with activation of TGFb1 and progression to chronic kidney disease. Our objective was to determine differences in the urinary excretion of inflammatory cytokines; OPN, ICAM1 and TGFb1, between SSNS (n=12), SRNS (n=12), and controls (CTR, n=12) in an attempt to identify specific biomarkers of steroid sensitivity or lack thereof. For this purpose, we used a protein array high-throughput technique and confirmed the findings by ELISA. In addition, we performed immunohistochemistry (IHC) for the above cytokines on renal biopsy samples. Mean age, gender, race, body mass index, and estimated glomerular filtration rate were not statistically different among three groups. There were no statistically significant differences between SSNS and SRNS in regard to the presence of hypertension, ACE treatment, and renal histology (p=0.99, 0.22, and 0.99, respectively) . Urinary excretion of ICAM1, OPN, and TGFb1 were statistically significantly higher in INS subjects vs. CTR. Urinary ICAM1 and OPN were higher in SSNS than in SRNS (p=0.005 and p=0.0002, respectively). However, the urinary excretion for TGFb1 was similar in SSNS and SRNS. The IHC failed to reveal differences in renal tissue expression of the studied cytokines. There was no correlation between urine and kidney tissue expression. In summary, our preliminary data suggest that urinary OPN and ICAM1 may serve as biomarkers of SSNS. This assumption needs to be tested prospectively. Methods: This is an interim report of this single center study on proteinuria in HIV positive children. There are 250 children aged 0-18yrs. registered in our HIV clinic. All children attending the outpatient clinic or seen on admission are studied. Questionnaires included bio and clinical data. Blood pressure was measured in all children. A clean catch or bag urine is obtained from all and urine biochemistry done on an aliquot. Patients found to have proteinuria 1+ or above are referred to the Nephrology Unit. Their urine is quantitated (timed urine collection), renal function, renal ultrasound and CD4 count estimated. ANF, LE cells, FBC including platelet count and Genotype will be assayed. A renal biopsy will be performed for nephrotic range proteinuria. Result: Eighty children positive for HIV have been studied. There were 41 males and 39 females giving a ratio of 1.1: 1. Their mean and median ages were 3.28yrs and 3.25 years respectively. All had normal blood pressures, renal ultrasound, and renal function. Fifteen of the 80 children (18.8%) had 30-100mg/dl proteinuria; 19 (23.8%) haematuria. Their mean CD4 + cell count was 316.9/mm 3 , range 180-1267. There was no significant difference between low CD4 + count and the presence of proteinuria (p>0.3). Seventy seven of the patients had vertical transmission of HIV; two acquired the infection from blood transfusion; one from scarification marks. Conclusion: There is a high prevalence of proteinuria among children with HIV infection in our region. HIV positive children should be screened and intervention instituted to avert or delay the onset of chronic renal failure. Carotid intima media thickness (cIMT) and brachial artery flow mediated dilatation (FMD) are novel indices of subclinical atherosclerosis. We studied these indices in children with nephrotic syndrome (NS) using high resolution ultrasonography (HRUS). 52 children with NS (42 SSNS;10 SRNS) of 24-207 months duration and 50 normal sibling controls underwent cIMT and FMD determination using a 7.5 MHz US probe. Routine biochemistry, lipid profile and hsCRP were carried out to look into associations with cIMT and FMD. Statistical analysis was carried out using EpiInfo 6.0. Cases and controls were similar in age, sex, growth and eGFR. Mean maximum cIMT (+-95% CI) (in mm) was higher in the NS group (0.435 +-0.014; range 0.333-0.570) vis-a-vis controls (0.398+-0.091; range: 0.345-0.490) (p<0.01). SRNS and SSNS cases were similar (0.441+-0.037 vs 0.434+-0.015 mm, p=0.36). Nephrotic children showed significantly lower FMD (10.56+-4.16% vs 17.39+-3.94%, p=0.02). cIMT and FMD varied with frequency of relapses in last 12 months (0.415+0.035mm, 10.27+-5.68% (no relapses); 0.449+-0.019 mm, 7.57+-5.39% (>3 relapses). Children with NS had mean hsCRP of 5.25+-0.57 mg/L. On univariate analysis, CIMT correlated with disease profile at onset (r=0.33, p<0.01), FMD (r=-0.23, p=0.02), male sex (r=0.23, p=0.02), BMI (r=0.23, p=0.02), cyclosporine exposure (r=0.5, p<0.01), total cholesterol (TC) (r=0.34, p<0.01), LDL (r=0.33, p<0.01), VLDL (r=0.29, p<0.05), triglycerides (r=0.33, p<0.05), atherogenic index (AI) (r=0.33, p<0.01) and creatinine (r=0.25, p=0.03). FMD correlated with systolic blood pressure, age, BMI, weight, total cholesterol, VLDL and triglycerides (p<0.05). To conclude, HRUS can detect early atherosclerosis using FMD and cIMT as the indices in children with nephrotic syndrome with disease duration of 20 years and more.

A ten-year old girl, who presented with biopsy proven acute severe changes of type 1 membranoproliferative nephritis (MPGN1) appears to have shown complete resolution of her disorder after nine months mycophenolate moffetil (MMF) (CellCept -Roche) added to relatively rapidly reducing steroids. She presented aged nine years with incidental finding of significant proteinuria and upper tract haematuria when presenting with abdominal pain. Blood pressure, chemical renal function and haematology were normal. C3 and total haemolytic complement were at the lower limit of normal. Renal biopsy showed light microscopy (LM) changes of markedly enlarged glomeruli with significantly increased mesangial cellularity and matrix, together with 'double contours' of basement membrane. Inmmunofluorescence (IF) was strongly positive for IgG and C3. Electron microscopy (EM) showed mesangial cell interposition into the basement membranes. She was treated with IV pulse methylprednisolone, followed by high dose oral prednisolone (PNL). After one month, MMF 500mg bd was added as PNL was tailed to alternate day therapy. PNL was reduced more quickly than usual due to difficulty with side effects and excellent clinical response. Within three months of MMF, proteinuria and haematuria had disappeared. Blood pressure and renal function have remained normal throughout treatment. After nine months, while on 0.5mg/kg alternate day PNL and 500mg bd MMF, repeat biopsy showed normal sized glomeruli on LM with no significant changes, no positive staining on IF and normal EM without mesangial interposition. This case suggests that MMF may be a key drug in management of MPGN1.

G. Stringini, E. Malagnino, F. Emma Bambino Gesu Children's Hospital and Research Institute, Department of Nephrology and Urology, Rome, Italy Serum creatinine values may vary considerably between normal subjects. These variations are in part secondary to differences in muscle mass, body composition and creatinine tubular secretion. In addition, low nephron number, which is influenced by genetic and intrauterine factors, is associated with increased incidence of arterial hypertension, late-onset proteinuria and chronic renal failure. Despite compensatory glomerular hypertrophy, autopsy data indicates that kidneys with fewer glomeruli tend to be significantly smaller. On these bases, we have hypothesized that a significant part of the variance of normal serum creatinine levels is related directly to individual differences in renal size. To test this hypothesis, we have reviewed the data of 1746 renal ultrasound examinations performed at our institution between 1991 and 2006. Patients were selected if they had conditions that should not influence renal size (low tract UTI, enuresis, bladder instability, idiopathic hypercalciuria), if they had normal GFR and an ambulatory blood pressure measurement. Analyses were performed after expressing renal length, serum creatinine levels and blood pressure values as Standard Deviation Scores (SDS) corrected for gender, age, height and weight, by multiple nonlinear regression analysis. A significant negative correlation was found between serum creatinine levels and renal length (p<0.001). When renal length measurements were grouped in quartiles, serum creatinine SDS was on average 0.37 SDS higher in the 1st quartile (small kidneys), in comparison with the 4th quartile (large kidneys). No correlation was found between kidney length and single measurements of ambulatory blood pressure. These data indicate that renal size is accountable for a significant part of the variance in serum creatinine levels that is observed in the normal pediatric population. Henoch-Schönlein Purpura (HSP) is the commonest small vessel vasculitis of childhood. Henoch-Schönlein Purpura nephritis (HSPN) is the major determinant of long term prognosis in HSP. The objective of this randomised controlled trial was to determine the effect of early prednisolone treatment on the development and progression of nephropathy in children with HSP. Methods: Children under 18 years of age, with a diagnosis of HSP, presenting to secondary care centres in England and Wales were randomly assigned to receive either placebo or prednisolone (2mg/kg/day (max 80mg) for 7 days, followed by 1mg/kg/day for 7days (max 40mg)). Patients, parents, paediatricians and investigators were 'blinded' to assignment of treatment or placebo. The primary outcome measure was the determination of the presence or absence of proteinuria, defined as urine protein: creatinine ratio (UP: UC) >20mg/mmol, 12 months after initial presentation in treated and untreated patients. Results: 353 children with HSP were randomised. 181 patients were assigned to receive prednisolone (group A) and 172 patients were assigned to receive placebo (group B). 36 patients in group A and 27 patients in group B did not complete the study. There was no difference in the incidence of proteinuria at 12 months, in patients receiving prednisolone (19/145) compared with those receiving placebo (15/145) OR=1.32, 95% CI 0.59-2.94, P=0.49. Conclusions: This is largest prospective randomised placebo-controlled trial of the role steroids in HSP in the literature to date. This study provides compelling evidence of absence of a beneficial effect of early treatment with prednisolone in the development of nephropathy 12 months after disease onset in children with HSP. While quality of life (QoL) is generally assumed to be poor on dialysis and to improve markedly after kidney transplantation, systematic assessments of QoL in children have not been performed to date. To date, we have examined general and health-related QoL in 35 children and adolescents with ESRD aged 4-16 years treated by hemodialysis (HD; n=7), peritoneal dialysis (PD, n=8) or renal transplantation (Tx, n=20), using a well-established instrument (KINDL) comprising an ageadapted set of questionnaires (KINDL). The obtained measures of overall and item-specific QoL were transformed to standard deviation scores (SDS). General QoL was close to normal and did not differ significantly between HD (-0.37±1.58 SDS), PD (-0.20±1.04) and Tx (-0.12±0.95). Psychological well-being was better in children on PD (0.54±1.04) than after Tx (-0.53±1.30, p=0.05) and on HD (-0.98±1.73, p=0.06). Physical wellbeing did not differ between treatment groups (HD: -0.39±1.19, PD: 0.10±1.21, Tx: (-0.16±1.06). QoL related to family life tended to be compromised in dialyzed (-0.87±1.58) vs. Tx children (-0.11±0.88, p=0.07) . Social interaction with friends was considered moderately impaired by all patient groups (HD: -0.89±1.92, PD: -1.15±1.26, Tx -0.82±1.44). Self-esteem was close to normal in all groups (HD: -0.3±0.85, PD: -0.27±1.35, Tx 0.21±.0). In summary, our preliminary results suggest that subjective QoL is remarkably good in children with ESRD, with surprisingly small differences between treatment modalities. Tx appears to be perceived beneficial with respect to the integrity of family life but provides poorer psychological QoL than PD, possibly due to the constant concern with graft loss.

Background: GFR is determined in the CKiD cohort study by plasma disappearance of iohexol (iGFR). Updated serum creatinine (Scr)-based formulas (sGFR=k ht/Scr) are needed for bedside clinical use. Objective: Derive formulas based on enzymatic Scr to estimate GFR in the CKiD study in children aged 1-16 yrs with sGFR of 30-90 ml/min/1.73 m 2 . Methods: From 253 children, height (ht, meters), iGFR, and Scr & BUN (mg/dL) by Bayer Advia 2400 were obtained. GFR was estimated from regression models: a(ht/Scr) b (35/BUN) c where a is GFR if ht=Scr and BUN=35; b and c are exponents. Results: 60% (n=152) were male; median age=11, Scr=1.4, BUN=31 and iGFR=38. Formulas ranged from an updated Schwartz formula (a=40.4, b=1, c=0; R 2 =0.66), to sex-specific (a=38.8, b=0.98, c=0 in girls, and a=40.5, b=0.79, c=0 in boys), which yielded R 2 =0.69, to the most complex (a=37.7, b=0.86, c=0.16 in girls, and a=39.7, b=0.69, c=0.16 in boys), which yielded R 2 =0.71, higher (p<0.001) than the R 2 of the updated Schwartz formula. By random selection of 127 of 253 subjects in 100 independent trials, we assessed the predictive ability of each formula on the other 126 observations. Sex-specific formulas produced unbiased results and increasing precision with increasing complexity. The updated Schwartz underestimated iGFR in boys by 3% (p<0.001) and overestimated iGFR in girls by 4% (p<0.001). Conclusions: Scr, ht, sex, and BUN together provided unbiased estimates of iGFR and explained 71% of its variability in children with iGFR of 14 to 76 ml/min/1.73 m 2 . Extrapolation to ht/Scr of 3 (normal body habitus and kidney function) and BUN of 10 yielded predictions of 118 ml/min/1.73 m 2 for GFR in girls and 104 boys. Including Cystatin C and broadening the GFR range to include normal levels are data being collected by CKiD to extend the formulas and provide wider clinical utility. F. Hussain, M. Mallik, A. Watson Nottingham University Hospitals, Children and Young People's Kidney Unit, Nottingham, United Kingdom Considerable variation exists between units in terms of techniques used for renal biopsy. The BAPN agreed an audit using published standards and a questionnaire was sent to all 13 UK paediatric nephrology centres. 11 agreed to a prospective audit between 1/1/05 and31/12/05. The survey revealed information leaflets are sent pre-biopsy in 5 (45%) centres with only one using play preparation. 6 (55%) routinely perform biopsies as daycase procedures (DC); 6 (55%) use general anaesthetic (GA). Realtime ultrasound is the favoured method in 8 (73%) of centres. Biopsies are performed by nephrologists only in 4 (36%), nephrologists with radiologists in 5 (45%) and radiology alone in 2 (19%). Of 531 biopsies (352 native), 164 (31%) were performed as a DC with 262 (49%) being done under GA. The mean age of patients was 11yrs (range 0.8±18.9yrs). The standard for the number of passes of native kidneys (<3 in 80%) was achieved in 86.4% with no significant difference between grade of operator or nephrology/radiology speciality. Standard number of passes in transplanted kidneys (<2 in 80%) was achieved in 73.4%. Adequate tissue was obtained for diagnosis in 97.5% (Standard >95%). The significant complication rate (macroscopic haematuria and/or delay indischarge) was higher than the set standard of <5% at 7.3%. There was no significant difference in complication rates whether the biopsy was performed as a DC or inpatient procedure (p=0.73) or whether GA or sedation was used (p=0.8).

Conclusions: The survey highlights significant variation in practice with limited use of preparation materials and DC. The results may enable individual units to reflect upon their techniques and complication rates and has stimulated constructive debate about indications and training issues. Objective: To characterize BP in children enrolled in the CKiD study, an observational cohort study of children 1-16y old with Schwartz estimated GFR of 30-90 ml/min/1.73 m 2 . Design/Methods: 3 BP's were obtained using an aneroid sphygmomanometer. GFR was measured by iohexol disappearance. BP was classified according to the 4th Report on BP in children. Hypertension (HTN) was defined as BP-95th percentile (uncontrolled), or as self-reported HTN plus current treatment with antiHTN meds. Pre-HTN was defined as BP 90th-95th percentiles. Results: 284 children (mean age 11±4y; 60% male) were studied. Mean GFR was 41±14 ml/min/1.73 m 2 and mean CKD duration was 7±4y. For SBP, 139/280 (49.6%) subjects had HTN of these, 59 subjects (21%) had uncontrolled HTN. 14 additional subjects (5%) had pre-HTN. Of subjects with systolic HTN, only 57% had measured SBP<90th percentile, and among the 73 subjects with measured SBP>90th percentile, only 32 (44%) were taking antiHTN meds. For DBP, 136/280 subjects (48.6%) had HTN of these, 53 subjects (19%) had uncontrolled HTN. 30 subjects (11%) had pre-HTN. Of subjects with diastolic HTN, just 52% had measured DBP <90th percentile, and among the 83 subjects with measured DBP>90th percentile, only 35 (42%) were taking antiHTN meds. Among children with GFR<50 ml/min/1.73 m 2 , the prevalence of systolic or diastolic HTN appeared to increase with decreasing GFR. Conclusions: A significant proportion of children enrolled in the CKiD study suffer from elevated BP. Nearly 40% of children with CKD had measured BP>90th percentile, and more than 50% of these children were not receiving antihypertensives, indicating that HTN in pediatric CKD is frequently under-or even untreated. Long-term follow-up of the CKiD cohort should reveal the effect of elevated BP on CKD progression. Background: We recently demonstrated elevated excretion of the putative urinary biomarkers TGF-β and ET1 in a large cohort of children with CKD. TGF-β excretion was highest in kidney disorders associated with marked tubulointerstitial fibrosis, such as obstructive uropathy, nephronophthisis and PKD. Aim: To investigate the course and predictive value of urinary TGF-β and ET1 excretion in children with CKD undergoing ACE inhibition (ACEi). Methods: To date, 165 patients have been followed for 2 years and 91 patients for 3 years in a prospective, interventional trial investigating the nephroprotective efficacy of ACEi w/out intensified blood pressure control. Results: Average BP was reduced to the mid normal range. Proteinuria initially decreased by 50%, but gradually reincreased to baseline levels within 3 years. Urinary TGF-β excretion, which was initially elevated 3-fold above healthy controls, continuously decreased during treatment from 32.6±31.5 ng/g creatinine to 27.4±20.7, 20.6±44.0, and 18.4±20.5 after 1, 2, and 3 years, respectively (p<0.001). In contrast, ET1 excretion increased by 100% within the first 2 years of follow-up. Neither baseline nor the change in TGF-β and ET1 excretion during treatment predicted the short-or long-term antihypertensive, antiproteinuric response to ACEi or CKD progression rate. Conclusions: The marked reduction of urinary TGF-β excretion probably reflects the antifibrotic effect of ACEi but, at least over 3 yrs of observation, does not predict the early and late course of proteinuria and CKD progression. Hence, urinary TGF-β appears to be a biomarker of tubulointerstitial disease activity rather than of global disease progression. The surprising increase of ET1 excretion may reflect the induction of compensatory hemodynamic mechanisms during ACEi.

Cardiovascular complications are the most important cause of death in pediatric patients with endstage renal disease. Therefore early diagnosis and treatment are very important. Brain natriuretic peptide (BNP) is released in response to volume overload or conditions that cause ventricular stretch. The aim of the study was to investigate whether BNP can be used for early diagnosis of cardiac complications in pediatric patients with ESRD. Twenty-four patients on peritoneal dialysis (mean age 13.3±4.4 years), 21 patients on hemodialysis (mean age 15.0±3.6 years) and 39 sex and age matched healthy children (mean age 12.4±3.0 years) were included the study. Plasma BNP levels were significantly higher in the patient group than those in the control group (590.4±765.8 vs 159.0±23.7 pg/mL, respectively, p<0.05), but there was no significant difference between hemodialysis and peritoneal dialysis patients. In patients with hypertension, BNP levels, left ventricular systolic and diastolic diameters were significantly higher than those in the patients without hypertension. In patients with higher CRP levels, BNP levels were significantly higher than those in the patients with low CRP levels. BNP levels had a positive correlation with left ventricular mass index (r=0.32, p=0.04) and a negative correlation with ejection fraction (r=-0.59, p<0.001) and shortening fraction (r=-0.55, p<0.001) significantly. There was no significant relation between BNP levels and anemia, dialysis duration, and dialysis modality. In conclusion, high plasma BNP level is significantly correlated with dilated left ventricle and it may be useful as a biochemical marker for identification of pediatric dialysis patients with cardiac dysfunction. We observed a high prevalence of left ventricular hypertrophy (LVH) and impaired LV contractility in children with stage II-III chronic kidney disease (CKD) (JASN 2006 , JASN 2007 . In a prospective, open-label assessment in 84 children receiving ACE inhibition (ramipril 6 mg/m 2 /d) with or without additional antihypertensive medication, we evaluated by echocardiography LV mass (LVM), geometry and myocardial mechanics at baseline and after 12 (N=65) or 24 mos (N=55) of treatment. LVH was defined by LVM index>38 g/m 2 and concentric geometry by relative wall thickness>0.375 (95 th normal percentile). LV systolic function was assessed at the midwall level by circumferential shortening (mS). Normalized 24 h mean arterial blood pressure (BP) was reduced from 1.3±1.4 at baseline to 0.0±1.4 and -0.5±1.0 SDS after 12 and 24 mos respectively. LVMI was reduced significantly after 12 (from 34.0±8.4 to 31.6±8.0 g/m 2.7 , p<0.02) and 24 mos (from 34.4±7.6 to 31.9±9.7, p<0.05). Of those patients presenting with LVH at baseline, LVM regressed to the normal range in 10/19 (53%) after 12 mos and in 10/18 (55%) after 24 mos. The prevalence of concentric LV geometry remained unchanged (baseline: 8%, 12mos: 9%, 24mos: 7%). Age and afterload-corrected myocardial function increased from 93±15% to 100±13% at 24mos (p<0.005). The changes in LVM and myocardial performance were independent of the randomized BP target and GFR. Change in LVM was correlated with change in hemoglobin level (r=0.30, p<0.05) and change in myocardial function with change in BP level (r=0.39, p<0.05).

In conclusion, fixed-dose ACE inhibition and tight BP control induce regression of established LVH in the majority of children with stage II-III CKD. This is associated with a normalization of myocardial contractility. Objectives of the study: Periods with insufficient erythropoietic activity may occur during the erythropoietin (EPO) treatment in chronic haemodialysis (HD). We determined the effects of a short-term suspension of EPO therapy on various oxidative stress parameters during a 12-week follow-up in HD patients. Methods: The antecedent epoetin beta (EB) treatment was suspended for 10 days. After that, 9 patients received EB two times a week and 7 patients received darbepoetin alfa (DA) once weekly. Concentrations of whole blood oxidized and reduced glutathione (GSSG, GSH) and various haematological parameters were determined weekly. Erythrocyte malondialdehyde (E-MDA) and the activities of erythrocyte superoxide dismutase, catalase and glutathione peroxidase were determined at weeks 0, 4 and 12. Results: The ratio GSSG/GSH was increased in both groups after continuation of the suspended EPO therapy (p<0.05 and p<0.01 week 1 vs. the baseline in the DA and EB group, respectively) and also at week 9 (p<0.01 and p<0.001 vs. the baseline in the DA and EB patients, respectively). The activities of the antioxidant enzymes were increased at week 4 in both groups (p<0.05 vs. the baseline for DA and p<0.001 vs. the baseline for EB), and returned to their week 0 levels by week 12. The E-MDA level decreased in both groups (p<0.05 week 12 vs. the baseline for DA and p<0.05 weeks 4 and 12 vs. the baseline for EB). Conclusions: A short-term suspension of EPO therapy caused characteristic time-dependent changes in the oxidative stress. The ratio GSSG/GSH increased at weeks 1 and 9. Activities of the antioxidant enzymes were elevated at week 4, resulting in an improvement in lipid peroxidation. These results might have implications in certain conditions with transient alterations in the erythropoietic activity in HD patients. RRF has been associated with better nutritional status both in adults and children on peritoneal dialysis and in adults on chronic HD. There are no data on the influence of RRF on nutrition in children on chronic HD.179 three-days dietary reports and simultaneous urea kinetic monitoring of 30 children, adolescents and young adults on chronic HD (age: 4.3-24.5 years) were retrospectively analyzed. Protein catabolic rate, an index of nutrition adequacy, was normalized by body weight (nPCR). In patients with RRF, total Kt/V (Kt/Vtot) was calculated summing HD Kt/V(Kt/VHD) and RRF (evaluated by residual urea clearance Ku-). In all patients, nPCR and dietary protein intake (nDPI) were significantly correlated (p<0.0001). Kt/Vtot was correlated with nPCR(p<0.0001) while correlation between Kt/VHD and nPCR was not significant (p: 0.11). In patients with RRF, Ku resulted significantly associated with nPCR (p<0.0001) while Kt/VHD was not (p: 0.10). nPCR was significantly higher in patients with RRF (1.46±0.41 vs 1.03±0.33 g/kg/day; p<0.0001). Patients on recombinant growth hormone (rhGH) treatment showed nPCR higher than those without rhGH (1.34±0.41 vs 1.01±0.39 g/kg/day; p<0.0001). However, in a multiple regression model including age, the use of rhGH, RRF, Kt/Vtot and Kt/VHD, nPCR resulted significantly associated only with RRF (b: 0.128; p<0.0001). Inconclusion: in children, adolescents and young adults on chronic HD treatment, RRF is associated with better nutrition. RRF positively affects nutrition independently from HD efficiency and rhGH effects. Possible hypothesis are a more selective (although decreased) depuration and the positive influence of water excretion maintenance on food intake. More efforts have to be made in order to maintain RRF in children on chronic HD. During the past three years, six women have undergone chronic haemodialysis during pregnancy at the Pediatric Renal Unit of the Adelaide Women's and Children's Hospital. Five have delivered normal infants at between 33 and 38 weeks gestation; one is presently at 28 weeks gestation, with an apparently normal fetus. Four were already receiving chronic haemodialysis at the time of conception; the others began dialysis at 20 weeks gestation. The protocol includes six days per week dialysis for at least two hours per treatment. A number of practical and emotional issues have arisen, with major potential psychosocial hazards, including: unplanned pregnancy due to ignorance of fertility; precipitation onto the dialysis program; acceptance of increased dialysis time; concerns regarding effects of drugs and dialysis/kidney failure on the fetus; the likelihood of prematurity; the perceived difficulties of motherhood while on a chronic dialysis program; loss of income, social networks and independence. The program has been successful due to the cooperative approach from the multidisciplinary team consisting of nephrologists, obstetricians, obstetric physicians dialysis nurses, midwives, dieticians, physiotherapists, psychiatrists and social workers. The social worker has provided counselling and coordinated transport and assistance with housework, childminding and other day to day tasks. Although the program has had overall success, there have been a number of pitfalls worth discussing, including those arising from the complex interactions between the members of the various disciplines, and those involved in maintaining the balance of clinical and psychosocial needs of the women. (median 17.5) , weight from 4.5 to 15.4 KgBW (median 9). The vascular access was a central catheter (KT) in 12 children, an arteriovenous fistula (AVF) in 6, AVF and KT alternatively in 14 patients. Duration of HD ranged from 1 to 63 m (median 14.5).35 dual lumen tunnelled cuffed KT were inserted in 26 children through the internal jugular vein [IJV]), surgically in 8, percutaneously in 27. All KT have had an immediate good function. Nine KT were exchanged over a guide wire for dysfunction. KT Infections with positive blood culture were successfully treated in 8 cases. Duration of KT ranged from 1 to 20 m (median 5). At the end of the follow-up, 7 KT were still in function, 6 removed for a mature AVF, 11 after renal transplantation (RT), 1 for improved GFR and 1 failed. Patency of the venous network after withdrawal of KT was assessed in 16 children (Doppler 3, MRI 13) and showed normal patency in 6, IJV thrombosis in 5, brachiocephalic thrombosis in 3 and stenosis in 2. Thirty AVF were created in 20 children, distal in 18 (60%). Immediate patency was obtained in all cases except 1. The median blood flow ranged from 350 to 1800 ml/min/m 2 (median 750). Following the primary surgery, 41 repeated surgical procedures included a superficialization of the vein in 10, refection for stenosis or thrombosis in 9, reduction of overflow in 3, 2 nd AVF creation in 10 and ligation after RT in 9. Percutaneous transluminal angioplasty was performed in 5 children. Duration of patency ranged from 1 to 168 m (median 36.5). In conclusion, HD is feasible in small children. Nevertheless, KT are associated with risk of venous occlusion and obtention of a reliable AVF frequently need several interventions, altogether leading to a limitation of HD indications in young children. 1994-2005, 60 (19%) were <2 years of age. The underlying disorders were congenital nephropathies in 70% (malformations 33%, hereditary 37%) and acquired diseases in 30%. Living related donation (LD) was performed in 59% and preemptive tx in 33%. Immunosuppressive (IS) protocol varied considerably between the countries and over time.1-year graft survival (GS) was 96% in LD and 87% in grafts from deceased donors (DD). GS improved significantly for DD grafts with time. The number of acute rejections (AR) during the first year posttx was significantly lower in LD recipients, in Tac-treated children and during the second half of the study period. This improvement over time was also seen in separate analysis of CYA-treated children. The proportion of rejection-free patients increased in all countries. Median height SDS at tx was -1.8 (-8.3 to +1.7)(boys -1.9, girls -1.6). Height SDS increased to -1.5 at 3 years posttx. Conclusions: GS results were excellent and the frequency of AR low, especially in children with LD grafts and Tac treatment. Interesting differences between the countries concerning donor source, preemptive tx, IS and use of protocol biopsies were found. N. Marcun Varda, A. Gregoric Maribor Teaching Hospital, Department of Pediatrics, Maribor, Slovenia Objectives: Essential hypertension (EH), identifiable in children, is associated with cardiovascular (CV) diseases in adulthood. The aim of our study was to evaluate the presence of some traditional and non-traditional CV risk factors in our children and young adults with EH in the search for additional CV risk. The prevalence of metabolic syndrome (MS) was also investigated. Methods: A total of 104 children and young adults, diagnosed with EH, were included in our study. They were compared with a control group of 50 healthy children, matched for sex and age, with regards to specific aspects in the history, body mass index (BMI), waist: hip ratio, full blood count, CRP, serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, uric acid, glucose, insulin, fibrinogen, homocysteine, apolipoprotein A1, apolipoprotein B and lipoprotein (a). In addition, the prevalence of MS was calculated. MS was defined as having three or more MS components according to the National Cholesterol Education Program's Adult Treatment Panel III criteria, tailored for children. Results: The differences in values of BMI, CRP, platelets, triglycerides, uric acid, apolipoprotein A1, apolipoprotein B and homocysteine between the hypertensive patients and the controls were statistically significant. In all hypertensives positive family history of hypertension in the first or second generation was revealed. Overweight (BMI >90 th percentile for age and sex) was identified in 40%, obesity (BMI >97 th percentile) in 24%, abnormal glucose homeostasis in 23%, high serum triglycerides in 42% and low HDL in 48% of the hypertensives. MS was present in 48% of these children and in 6% of our controls. Conclusion: We demonstrated that children and young adults with EH differ from the population of healthy children in some specific CV risk factors, and are therefore at an increased CV risk. Background: RTD is a rare autosomal recessive disease of differentiation of fetal kidneys with poorly developed proximal tubules. Fetal and neonatal findings include oligohydramnios, preterm birth and neonatal death due to pulmonary hypoplasia, anuria and hypotension. Mutations in genes in the renin-angiotensin system (RAS), encoding for angiotensinogen, renin, angiotensin converting enzyme and angiotensin II receptor type 1, have been revealed. We report the first RTD patients surviving the neonatal period and still being alive. Both patients had affected siblings demised in utero or neonatally. Case 1: Oligohydramnios, birth at 38 weeks, 2850 grams. Neonatal course: Pulmonary hypoplasia, pneumothorax, hypotension and anuria with ventilation (4 weeks) and dialysis (2 days) . Current findings at 15 years: creatinine 200 umol/l, normal blood pressure. Genetic and functional analysis: Homozygous mutation of Angiotensinogen gene (1124G-A); very low angiotensinogen concentration (21.4 ng/ml; normal 1024-275), absent plasma renin activity (normal 1.5-3.0 ng/ml/h) despite very high active renin (199 pg/ml; normal 22-11). Case 2: Oligohydramnios, birth at 35 weeks, 2520 grams. Neonatal course: Mild respiratory distress, hypotension and anuria with oxygen (1 day) and dialysis (5 months) . Current findings at 10 years: Renal transplantation at age 4 years, good graft function. Genetic and functional (as neonate) analysis: Homozygous mutation of Renin gene (1124G-A); very low active renin (<2.5 pg/ml; normal 24-850). Conclusions: RTD is caused by inactivating mutations in genes encoding the RAS resulting in chronic low perfusion pressure of the fetal kidney. Genetic and functional analysis of RAS contributes to diagnosis of RTD. This observation extends the RTD phenotype from a uniformly fatal to a more favourable disease. Objectives of study: To evaluate the relationship between serum uric acid (UA), new onset essential hypertension (EH) and endothelial dysfunction (ED) in the youth. Methods: 29 subjects with ABPM proved new onset EH (aged 19, 9±3, 5 years, BMI 28, 9±3, 5 kg/m 2 ), 36 overweight/obese normotensive youth (OO) matched for age and BMI, and 73 age matched healthy normotensive controls (NT) with normal weight were enrolled. UA, total cholesterol, HDL, LDL, triglycerides and creatinine were analyzed in blood, glomerular filtration rate (GFR) was calculated according to Schwartz formula and endothelial function was assessed using flow-mediated dilation (FMD, %). Results: New onset EH was associated with overweight/obesity in 90% of subjects. Serum UA levels were significantly higher in EH than OO (381±92 vs.336±72 umol/l, respectively, p<0, 05), in EH than NT (381±92 vs.277±62 umol/l, respectively, p<0, 0001), and in OO than NT (336±72 vs.277±62 umol/l, respectively, p<0, 0001). Total cholesterol, HDL, LDL and triglycerides were significantly higher in EH and OO compared with NT (p<0, 0001). No significant differences were found in lipidograms between EH and OO. Serum creatinine and GFR did not differ significantly between the groups. FMD was significantly lower in EH comparing with OO and NT (5,49±4,83 vs.12,75±3,47 vs. 14,55±5,32%, respectively, p<0, 0001) and in OO comparing with NT (12,75±3,47 vs.14, 55±5,32%, respectively, p<0, 05). Conclusions: New onset EH in the youth is associated with overweight/obesity, higher serum UA and ED. UA may play a causal role in the pathogenesis of EH and commonly with EH and proatherogenic serum profile contributes to ED in overweight/obese hypertensive youth. Objective of study: Fibromuscular dysplasia (FMD) is a systemic arteriopathy of the small and medium sized vessels. It is the first cause of renal arterial stenosis (RAS) in childhood. The aim of this study was to describe the natural history of FMD in children.

We analysed all the data of 12 children with FMD. Results: Mean age at diagnosis was 4 years 9 months old. HBP was discovered fortuitously in 5 cases, after symptoms of malignant hypertension in 7. In all cases BP values corresponded to severe hypertension (mean BP of 190/105 mmHg). Extra renal localizations were found in half of the patient, and the most frequent pathological arteries were the superior mesenteric and the carotida. The mean number of arterial stenosis at diagnosis was 2 per patient. Seven patients had a primary FMD with familial history for 1 patient. In the others FMD were associated with polymalformatif syndromes: reported by Grange (2), Moya-Moya disease (2), neurofibromatosis type I (1). After a median follow-up time of 81 months the number and severity of stenosis increase at 6 arteries per patient. These lession, although to a lesser extend, were already observed as soon as 30 months of follow-up. Percutaneous transluminal renal artery angioplasty were proposed in 6 cases when the BP was uncontrolled indeed a multi antihypertensive therapy with severe renal stenosis (>80%) or when renal growth was impaired. Prognosis is severe with cardiologic complications (10/12) and 1 death. Conclusions: Intimal form of FMD accounts for the majority of multivisceral FMD. At diagnosis several hypertension is almost present. Vascular ultrasonography imaging techniques is usefull in follow-up. A conservative treatment has to be privilegied. This disease is evolutive with increase of pathological arteries number, aggravation of stenosis degree and sometimes renal function impairment. Objective: The effect of over weight on blood pressure elevation (BP) is more frequently present in childhood. Several studies have demonstrated the efficacy of angiotensin-converting enzyme inhibitors (ACEI) therapy in obese hypertensive adults, but data on children are very limited. Methods: 110 obese (BMI: Z score >2.5 SD) primary hypertensive (systolic ordiastolic blood pressure >95th) children (aged 6-7 years) were enrolled to this single centre prospective study. Patients received ramipril (0.1-0.15 mg/bwkg/day) once daily. Office and ambulatory bloodpressure measurements and serum biochemical analysis were performed at start and after 1 and 6 months of treatment. 36 patients (23,7%) hadimpaired glucose tolerance (IGT) on oral glucose tolerance test (OGTT). Results: 94 (85,5%) patients completed the six months ramipril therapy. Reduction in 24-hour mean arterial pressure (MAP) was 4, 95 mmHg (-1, 02SD) after 1 month and 10, 14 mmHg (-2,05 SD) 6 months treatment respectively. BP was reduced with equal efficacy during day-and night time. 3/110 (2, 7%) patients were lost during the follow-up. 15 (15,9%) patients with high uric acid levels also were treated with allopurinol. Eleven patients (10%) received second antihypertensive medication because of the blood pressure remained uncontrolled. (7 pts metoprolol, 4 pts amlodipine) 8 (7,2%) patients suffered recurrent cough, but otherside effect has not observed. The serum glucose and insulin levels havenot changed significantly during the follow-up. Conclusion: Oncea day given ramipril significantly decreases the blood pressure inobese hypertensive children. It is effective, tolerable and safe bloodpressure lowering monotherapy in childhood. Further studies and longer follow-up are necessary to prove its long term beneficial effect in the childhood metabolic syndrome combined with hypertension.

HW. Zhang, J. Ding, F. Wang, YF. Wang Peking University First Hospital, Department of Pediatric Nephrology, Beijing, People's Republic of China Objectives of study: Females with X-linked Alport syndrome (XLAS) have variable phenotypes, from microscopic hematuria to chronic renal failure, which can not be clarified solely by mutation features of COL4A5 gene. X-inactivation has been suspected to be one of the responsible reasonsfor this phenomenon, but no definite correlation has been demonstratedso far. In order to confirm whether the phenotypes of XLAS femalescorrelate with X-inactivation, we analyzed the Xinactivation patternsin peripheral blood cells in 36 XLAS females and in skin fibroblasts in12 XLAS females. Methods: The X-inactivation analysis was performed using HpaIIpredigestion of DNA followed by polymerase chain reaction (PCR) of thehighly polymorphic CAG repeat of the androgen receptor (AR) gene. Results: Results showed that the average X-inactivation levels of the mutant allele decreased while the degree of proteinuria increased, there was anegative correlation between the degree of proteinuria and theX-inactivation ratios of the mutant allele in blood cells (r=-0.474, P=0.006). However, there was no correlation between the degree of proteinuria and the X-inactivation ratios of the mutant allele in skin fibroblasts (r=-0.131, P=0.701). Though 7 of 12 patients (58.33%) had the similar X-inactivation ratios in both blood cells and skin fibroblasts, there was also no correlation between the X-inactivation ratios of the mutant allele in skin fibroblasts and that in peripheral blood cells (r=0.180, P=0.575). Conclusion: We concluded that the X-inactivation ratios in blood cells correlated with the degree of proteinuria, which might explain partially the diverse phenotypes in female XLAS patients. More studies, including post-transcription regulation, environmental factors, and so on, are still needed. Objective: To report Frasier Syndrome (FS) with WT1 mutation and abnormal expression of podocyte molecules which is the first case in Mainland China. Methods: Peripheral blood cells were analyzed for chromosome karyotype and WT1 gene mutation. The ratio of +KTS/-KTS isoforms was quantified with GeneScan and GeneScan software. Expressions of podocyte molecules were detected by immunohistochemical staining. Result: The patient presented with steroid-resistant FSGS and male pseudohermaphroditism. The WT1 IVS 9 +5 G>A mutation was found in one allele in the proband, but not in her parents. The ratio of +KTS/-KTS was 0.67 in the proband, and was 1.35 and 1.42 in her mother and father, respectively. Podocyte molecules expression altered in normal-and abnormal-appearing glomeruli. WT1 expression showed diffuse nuclear staining with less obvious speckles compared with that in controls. WT1 (antibody against C-terminal) displayed strong, normal, faint and negative stained podocyte nuclei within the same glomerulus. The staining intensity of WT1 (antibody against the N-terminal) was very faint. Conclusion: Taking clinical data, pathology, karyotype analysis and genetic testing together, we diagnosed the first case of FS in Mainland China, which prompts there might be more cases underdiagnosed. WT1 displayed diffuse nuclear staining with less visible speckles compared to controls, supporting the view of the differential nuclear localization of KTS isoforms. Our study further confirmed that WT1 mutation resulted in abnormal expression of podocyte molecules in glomeruli of FS, though we did not know whether this phenomenon directly or indirectly resulted from loss of WT1 regulation. Dent disease is an X-linked disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, calcium nephrolithiasis and the development of renal insufficiency after the middle age. So far, two genes responsible for the development of Dent disease have been identified, i. e., CLCN5 and OCRL1. OCRL1 was originally identified as a causative gene for Lowe syndrome. In Japan, Igarashi et al. described for the first time that idiopathic tubular proteinuria in Japan is identical to Dent disease by mutational analyses. Most of Japanese patients with Dent disease are identified by annual urinary screening as chanced proteinuria and several clinical phenotypes, such as incidence of nephrocalcinosis and long term outcome of renal function remains to be elucidated. Furthermore, identification of OCRL1 as a second causative gene for Dent disease has made the understanding of Dent disease more complex. Here we report 90 patients with Dent disease phenotype with the results of genetic analyses and clinical features. Out of 90 patients in 90 different families, 58 mutations (64%) in CLCN5 were identified. In the 32 patients with no CLCN5 mutations, genetic analysis in OCRL1 is ongoing, and at the moment 4 different mutations in OCRL1 ((I127stop, R301C, R476W and R318H) were identified. The remaining patients are now beeing investigated. Among the patients in whom CLCN5 mutations were detected, hypercalciuria are not always present. In several elderly patients, mild renal function impairment is present. There are similar clinical phenotypes between patients with CLCN5 or OCRL1 mutations, but serum levels of LDH and CK are likely to be higher in those with OCRL1 mutations. In summary, we will present genotype and phenotype heterogeneity in Japanese Dent disease, and will discuss the clinical spectrum of Dent disease.

A. Gulati 1 , S. Sethi 1 , J. Lunardi 2 , M. Kabra 1 , N. Gupta 1 , P. Hari 1 , A. Bagga 1 1 All India Institute of Medical Sciences, 1st Department of Pediatrics, New Delhi, India 2 Hôpital de La Tronche, Genetics, Grenoble cedex. France, France Objectives: To study the clinical features and genetic basis of patients with Lowe syndrome and identify female carriers. Methods. Case records of 6 patients with Lowe syndrome presenting to this hospital, between 3-7 yr old, were reviewed. The clinical features were recorded and glomerular and tubular functions assessed. A detailed genetic analysis was performed on DNA extracted from peripheral blood of patients and their mothers, which involved sequencing of all 23 exons of the OCRL1 gene. Results: All patients showed failure to thrive, bilateral congenital cataracts, refractory rickets, delayed motor and language milestones and proximal renal tubular acidosis with Fanconi syndrome. The mean Schwartz GFR was 90 ml/min/1.73 sq. m. Genetic analysis showed distinct mutations of OCRL1 gene in all patients studied. We report 4 new mutations having identified the variants c.779 A>G and c.853 G>T in exon 10, the variant c.1183_1184 ins T in exon 12 and c.2351-2 A>G in intron 22 in 4 independent patients. We also found 2 previously described mutations involving the region c.2309_2310 del TG and c.2377 C>T in exon 21. Four of 6 mothers were heterozygous carriers. All genotypically proven carriers showed characteristic lenticular opacities. Conclusion: The identification of mutations in the OCRL1 gene provides confirmation of the diagnosis of Lowe syndrome. The new mutations described in north Indian children expand the range of mutations that give rise to this condition. These observations have important implications for molecular diagnosis and genetic counseling in families with Lowe syndrome. Juvenile nephronophthisis (NPH), an autosomal recessive nephropathy, is the most common genetic cause of chronic renal failure in childhood. In 10-15% of known cases, NPH is associated with Joubert syndrome (JS), a neurological disorder described in patients with cerebellar ataxia, mental retardation, hypotonia and respiratory dysregulation. Mutations in three genes, AHI1, NPHP1 and NPHP6 have been identified in patients with NPH and JS. As NPHP1 mutations usually cause isolated nephronophthisis, the factors which predispose to the development of neurological symptoms in some patients are poorly understood. To determine such genetic factors and to assess the mutation rate of AHI1, NPHP1 and NPHP6 in NPH and JS, a cohort of 30 families with NPH and at least one JS-related neurological symptom was screened for mutations in these genes. Thirteen (43%) and 8 (27%) unrelated patients were homozygous or compound heterozygous for NPHP1 and NPHP6 mutations, respectively. In 4 patients (13%) without NPHP1, NPHP6 or AHI mutations, mutations in a novel gene (NPHP8/CORS7) encoding a ciliary protein have been identified. Interestingly, 7 of the 13 patients with NPHP1 mutations carried either a heterozygous truncating mutation in NPHP6 (1 patient), a heterozygous missense mutation in AHI1 (1) or the AHI1 variant R830W (5) . The variant R830W affects an amino acid conserved in vertebrates and predicted to be 'possibly damaging' by PolyPhen software. In conclusion, NPHP1, NPHP6 or NPHP8 mutations can be found in 83% of patients with NPH and JS in our cohort. Our finding that half of all patients with NPHP1 mutations carry a mutation or a damaging variant in NPHP6 or in AHI1 strongly supports the notion that epistatic effects provided by these genes contribute to the appearance of neurological symptoms in patients with NPHP1 mutations. Molecular cytogenetic techniques such as array-based CGH have been instrumental in the identification of microimbalances associated with syndromic phenotypes. We investigated 10 patients with unclear syndromic nephropathies (e. g. urinary tract malformations, focal segmental glomerulosclerosis, and persistent hematuria/proteinuria) and additional clinical features, such as mental retardation, heart defects or growth abnormalities. Array-CGH analysis was performed with a whole-genome array with 8000 large insert clones providing an average resolution of <0.5Mb. Results: In one 16-year old female patient presenting with microhematuria, proteinuria, mental retardation including severe speech impairment, senso-neuronal hearing loss, and recalcitrant focal epilepsy, we detected a microdeletion in chromosomal bands Xq22.3-q23. This deletion was verified by FISH, found to be uniallelic, 2.2-3.7Mb in size, and not to be inherited from the mother. Electron microscopy of kidney biopsy showed splitting of the lamina densa and a thin basal membrane, which is diagnostic for Alport syndrome. High-resolution cranial magnetic resonance imaging including white fibre tracking revealed a severe neuronal migration disorder with subcortical band heterotopia (double cortex syndrome), i. e. a second band of cortical neurons within the white matter below the true cortex. Conclusions: In 10 patients with unclear syndromic nephropathies, we identified a female with a contiguous gene syndrome at Xq22.3-q23. The microdeletion includes the X-linked Alport syndrome gene COL4A5 and the LISX gene associated with subcortical heterotopia, mental retardation and epilepsy. Thus, the phenotype observed in our female patient combines features of the AMME-complex (Alport syndrome, mental retardation, midface hypoplasia, elliptocytosis) with X-linked lissencephaly. (29 F, 29 M; 17.80±6 .50 yrs, hemoglobin 9.67±1.08 gr/dl, ferritin 2827±1895 mg/dl) were enrolled. Lipid profile, acute phase proteins (APPs) were measured. Renal tubular functions, plasma VEGF level, urinary NAG/Cre ratio were determined. ABPM and IMT measurements were performed. The results were compared with healthy controls. Results: Mean 24-hour, day and night systolic-blood pressure (SBP), diastolic-BP (DBP) and mean arterial pressure values were comparable to that of control group. Dipping in DBP was less in TM (19.03% vs 23.73%; p<0.05). The ratio of patients with less than 10% dipping in SBP (non-dippers) was higher in TM (51.9% vs 35.0%, p<0.05). Mean plasma VEGF level was 30.16±22.95 pg/ml [2.69-112.25] in TM, was within normal range (<10 pg/ml) in controls. APPs were normal. IMT of common carotid artery (CCA) was 0.455±0.050 mm in TM group and 0.273±0.039 mm in controls, (p<0.01); IMT of internal carotid artery (ICA) was 0.344±0.037 mm in TM group and 0.203±0.041 mm in controls (p<0.01). Positive correlations were found between VEGF and microalbuminuria, b2-microglobulin and homosistein; between NAG/Cre and microalbuminuria; between CCA-IMT and age, and a negative correlation between CCA-IMT and ferritin. Conclusions: Renal tubular damage, abnormalities in ABPM, increase in VEGF and increase in CCA-IMT and ICA-IMT occur when the patients are asymptomatic and routine laboratory test are normal. Optimal hemoglobin levels and deferoxamine therapy do not prevent the development of renal and vascular damage.

L. Sylvestre 1 , E. Santos 1 , P. Granzotto 2 , E. Siqueira 2 , L. Moreira 2 , L. Rispoli 2 , N. Mendes 2 , R. Meneses 1 1 Hospital Pequeno Principe, Pediatric Nephrology, Curitiba, Brazil 2 Centro Universitario Positivo Unicenp, Curitiba, Brazil Introduction: Hypertension is frequently underdiagnosed in children. Early diagnosis and a planned follow-up is helpful in detecting and preventing the harmful long-term consequences of hypertension. Therefore, we created a specific outpatient clinic to have a better follow-up of these patients. Material and Methods: We reviewed the files of patients from the outpatient clinic of hypertension, from the Dept. of Pediatric Nephrology in Hospital Pequeno Principe, Curitiba, Brazil, followed for more than 3 months, from March 2005 to December 2006. We analyzed demographic and anthropometric data, diagnosis, staging of hypertension, presence of target-organ damage and treatment. Results: 72 patients were eligible, 40 boys, mean age at the first visit 6.3 years old, mean follow-up of 11 months. Mean BMI=18.92 (44% overweight and obese). Secondary hypertension was present in 47% of the cases, predominantly due to parenchymal renal disease; essential hypertension associated to overweight and obesity in 19 patients (27%) and there was no established diagnosis yet in other 19 patients. Fifty-five patiens performed at least one ABPM of 24 hours, 46 showed hypertension. Twelve from 69 patients showed left ventricular hypertrophy and 18 from 61 patients had abnormalities of the retinal vasculature associated to hypertension. The most frequent drugs used to treat hypertension were ACE inhibitors (49) and calcium channel blockers (47). Conclusion: Our data are in accordance that secondary hypertension is frequent in children, mostly associated to renal disease. Furthermore, we could detect a large number of obese hypertensive children and adolescents. Target-organ abnormalities are not as frequent as in adults but need to be monitored. Intrauterine growth retardation (IUGR) is characterized by low nephron number with or without reduced kidney size. Leptin, an important hormone in the regulation of body fat massand weight, is decreased in fetuses with IUGR. In the present study, weexamined the effects of leptin in a metanephric mesenchymal cell line MS7. MS7 is generated from the metanephroi of embryonic day 11.5 homozygous mouse transgenic for H-2Kb-tsA. Incubation of MS7 withleptin 1, 10, 50, 100 or 500 ng/mL for 24 h did not affect either [ 3 H]-thymidine incorporation or cell number. On the other hand, [ 3 H]-leucine incorporation was significantly increased by leptin in a dose dependent manner (120±9%, 123±2%, 130±3%, and 131±3% of control by 1, 10, 50, and500 ng/mL, respectively). Protein/DNA was also increased 1.7-fold by leptin 10 ng/mL. Leptin 10 ng/mL activated both ERK and p38. The levels of phosphorylated-ERK (P-ERK) and phosphorylated-p38 (P-p38) , as assessed by Western blot analysis, started to increase at 10 min, peaked at 30 min (1.6-and 1.7-fold increase respectively) remaining elevated at 1, 2, and 6 h, and began to decrease at 12 h returning to the baseline level at 24 h. The levels of P-ERK and P-p38 at 30 min were increased by leptin in a dose dependent manner (1.2-, 1.6-, 1.6-, and 1.7-fold increase by 1, 10, 100, and 500 ng/mL respectively). The levels of total ERK and p38 remained unchanged. Increase in [ 3 H]-leucine incorporation stimulated by leptin 10 ng/mL was completely inhibited by coincubation with a MEK inhibitor PD98059 5 μM or a p38 inhibitor SB203580 5 μM. These results demonstrate that leptin induces hypertrophy of metanephric mesenchymal cells via ERK and p38. The hypertrophic effect of leptin may play a role in normal renal development and may explain reduced kidney size in a hypoleptinemic state, IUGR. Objectives of study: To investigate the mechanism of nephron deficit in rat model of intrauterine growth retardation (IUGR). Methods: A rat model of IUGR was built by maternal low-protein (6%) dietthroughout pregnancy. Newborn male pups were chose as our studyobjects. The proliferation and apoptosis in kidney was showed by Ki-67 detection and TUNEL method. Expression of WT1, Bcl-2, Bax, and p53 mRNAs in renal tissue were examined by real-time PCR, and expression of WT1 and Bcl-2 gene products in renal tissue were examined by immunohistochemistry and Western blot. The final number of glomeruli was determined at 2 weeks of age when nephrogenesis has finished. Results: At 2 weeks postnatally, IUGR offspring had fewer glomeruli per kidney than those in controls (P<0.001). In IUGR newborns, TUNEL positive cells were more numerous in the nephrogenic zone. RenalWT1 and Bcl-2 mRNA levels were significantly reduced in newborn IUGRpups, and the Bcl-2 mRNA/Bax mRNA ratio was also decreased, but therewas no change in the expression of p53 mRNA. In IUGR newborns, the WT1and Bcl-2 protein expressions were significantly decreased, and the irimmunostaining were also suppressed in the nephrogenic zone. Conclusions: These results suggest that reduction of nephron number in IUGR rat may be associated with enhanced apoptosis in kidneydevelopment. Decreased WT1 and Bcl-2 expressions and reduction of the Bcl-2/Bax ratio may contribute to the molecular mechanisms behind these findings. Objective of the study: The aim of this study was to identify risk factors for urinarytract infection (UTI) during follow-up of children with isolatedantenatal hydronephrosis. Methods: Between 1999 and 2006, 192 patients were diagnosed with isolated fetal renal pelvicdilatation (RPD) and were prospectively followed. After initialclinical and imaging evaluation, US scans, clinical examination, andlaboratory reviews were scheduled at 6-month intervals. The event ofinterest was time until occurrence of first episode of UTI. Cox's regression model was applied to identify variables that wereindependently associated with the UTI. Results: A total of 192patients were included in the analysis (140 boys and 52 girls) Themedian fetal RPD was 10 mm (IQ range, 7.8±14) and 95 patients (49.5%) presented bilateral RPD. Seventyeight (41%) infants presented urinarytract anomaly. The most frequent detected uropathy was UPJO (55), followed by primary VUR (16), and megaureter (7). Median follow-up timewas 24 months (IQ range, 12-39 months). During follow-up, UTI occurred in 27 (14%) of the 192 children. The incidencerate of UTI was 5 episodes per 1000 person-month. The incidence rate of UTI has decreased from 7.2 episodes per 1000 person-month in the first year of life to 3.3 in the second year, and to 1.4 after the third year. By survival analysis, the risk of UTI for the whole series was estimated in 8.5% at 12 months, 14% at 24 months, and 21% at 36 months of age. After adjustment, two variables were independent predictors of UTI during follow-up: female gender (RR=2.2, 95% CI, 1.04-4.8, P=0.03) and presence of uropathy (RR=4.6, 95% CI, 1.8-11.4, P=0.001). Conclusion: According to findings, in a cohort of antenatal hydronephrosis, girls with VUR or urinary tract obstructionhad a higher risk of UTI during follow-up. Objective of the study: To identify predictive factors of resolution of fetal renalpelvic dilatation (RPD) in a cohort of medically managed children. Methods: Between 1999 and 2006, 192 patients were diagnosed with isolated RPD and were prospectively followed. Of 192 infants, 165 (86%) were clinically managed. After initial clinical and imaging evaluation, US scans, clinical examination, and laboratory reviews were scheduled at 6-month intervals. The event of interest was RPD resolution, regardedas renal pelvis <5 mm on two consecutive renal sonograms. Cox's regression model was applied to identify variables that were independently associated with the event.

Results: A total of 165 patients were included in the analysis and uropathy was diagnosed in 51(31%) infants. Median follow-up time was 22 months (interquartile range, 12 to 37 months). During follow-up, 60 (36%) patients presented RPD resolution. By survival analysis, the estimate of RPD resolution for the whole series was 23% at 12 months, 39% at 24 months, and 42% at36 months of age. The median time for RPD resolution was estimated at 49 months (95% CI, 36-62).

In the survival analysis, three variables were found to be significantly associated with resolution of RPD during follow-up: mild fetal RPD, grades 1-2 (SFU grading system), and presence of uropathy. After adjustment, only absence of uropathy remained as an independent predictor of RPD resolution (RR=3.6, 95% CI, 1.7-7.4, P<0.001). Conclusion: According to these findings, it was estimated that RPD resolution occurs in about half of the patients without uropathy at 2 years of age.

Objective: To study clinical and pathological characteristics of antineutrophil cytoplasmic autoantibody (ANCA)-positive glomerulonephritis(GN). Methods: clinical data of thirteen patients during 5 years, with ANCA-positive GN were analyzed. Results: Of patients with ANCA-positive GN with an average age of 8.8±2.5 (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) years, 11 patients were female and 2 were male. The average course was 2.2±1.9 months. 8 cases onset between December and February. There was 3, 5, 2 cases whose chief complaint on admission was anaemia, swollen and hematuria respectively. The main clinical symptoms were: anaemia (100%), hematuria/proteinuria (100%), renal functional lesion (100%), edema (76.9%), oliguresis (38.5%), hypertension (61.5%), arthralgia (30.8%), rash (15.4%), abdominal pain (46.2%), fever (7.7%). Laboratory tests: BUN, Scr and ESR were high while hemoglobin was low in all patients. MPO-ANCA was positive in 13 cases C3 was normal in 4 cases and low in 9 cases. Pathology features: All glomeruli are affected and show different degree of Segment and glomus sclerosis. There was different degree of capsula glomeruli thickening. glomerulus capillary loop was necrotic, nuclear leukocytes and cell debris could be seen. Inflammatory cell interstitial infiltration with lymphocyte and plasmocyte. Endotheliocyte of small vessels of interstitial was swelling and vessel wall was edema, necrosis and glassy degeneration. immunofluorescence showed no or small immune complex deposition and showed pauci-immune GN. Conclusion: Onset of patients with ANCA-positive GN was hiding and there were nonspecific clinicalsymptoms in the early stage that reduced late diagnoses until ESRD. Female patients was predominant. Renal pathology showed Segment necrotic nephritis interstitial inflammation and polyangitis. The disease had unfavourable prognosis. Background: renal function maturation isn't achieved at birth. VLBW infants exposed to intensive care have an increased risk of developing renal function impairment. Moreover, we showed that IBU was associated with a significant impairment in renal function at one week of life in VLBW infants. Objective: to evaluate renal function development in infants treated with IBU for PDA closure as compared to infants not exposed to IBU, during the first month of life. Methods: multicentric prospective cohort study of 27 to 31 weeks gestation (GA) infants exposed or not exposed to IBU within the first 5 days of life. Infants presenting with renal impairment at birth, urinary tract malformation, or contraindication to IBU were excluded. Infants exposed to IBU were paired to Controls according to GA, centre and CRIB score. Creatinine clearance (mL/min/1.73 m 2 ) was measured for glomerular filtration rate evaluation. Fractional excretion of sodium (FENa%), micro-albuminuria (mg/L) and alpha1-microglobinuria/creatininuria (1/UCr: mg/mmol) were also measured once a week up to 1 month of life Results: 120 infants were studied, half exposed to IBU. Birth weight was 1100±278 g (Mean±SD), and GA 28±1 wks. Results are presented in the table: *p=0.02;**=0.01;***<0.01.

J. Rouillard Lafond, MP. Morin, C. Girardin Centre Hospitalier Universitaire de Sherbrooke, Département de Pédiatrie, Sherbrooke, Canada Objectives of study: Many studies have focused on the negative effects of low birth weight, especially caused by intra-uterine growth restriction, on adult renal function. However, few have addressed the impact of extreme prematurity (<28 weeks) on renal function of these children during their later childhood and adolescence. The aim of the present study is to estimate the renal outcome of this population, by determining blood pressure, glomerular filtration rate, fractional excretion of sodium and microalbuminuria in 24 children (11 girls and 13 boys) aged 7 to 18 years old (mean age 12) born between 24-28 weeks of gestation (mean: 27 weeks). Methods: During one encounter, height, weight and blood pressure were measured for each subject. Blood tests were conducted to quantify creatinine, electrolytes and cystatin C. Microalbumine, creatinine and electrolytes were dosed in one micturition. Pertinent risk factors of renal damage in their perinatal history were noted. Results: Renal insufficiency, defined by a clearance of less than 90 ml/min/1,73 m 2 , was present in 3 subjects (22%) when estimated by Schwartz formula (84,67-86,20 ml/min/1,73 m 2 ) and in 1 (4%) when estimated by Cystatin C (47,4 ml/min/1,73 m 2 ). Furthermore, 5 (20%) children presented an elevated fractional excretion of sodium (1, 19-1, 56%) . Finally, 8 children (33%) presented microalbuminuria, with albumin/creatinine ratio greater than 2,0 mg/mol (2,04-17,25 mg/mol) . Those children presented more episodes of hypotension during neonatal period (p=0,028) and have a tendency to have had neonatal asphyxia more than the others (p=0,065). Conclusions: These results suggest that children born extremely preterm may present renal insufficiency and sign of tubulopathy as early as adolescence, with microalbuminuria possibly announcing upcoming glomerulopathy.

Organogenesis isregulated by epithelial-mesenchymal interactions that take place in theembryonic kidney between the metanephric mesenchyme (MM) and theepithelium of the ureteric bud (UB). The MM expresses signals thatregulate ureteric branching while the UB signaling leads to inductionof nephrogenesis. As a response to the UB signals the MM cellscondense, aggregate, epithelialize and undergo simple morphogenesis togenerate segmented nephrons during kidney organogenesis in connectionto ureteric bud branching. We reported earlier that mutagenesis of Fgf8 function from the whole embryonic mesoderm leads to kidney failure. Activation of Wnt-4 gene expression encoding another essential signal for nephrogenesis also depends on Fgf8 function (Perantoni et al., 2005) . Given the important role of Fgf8 in kidney development we targeted Fgf8 roles in urogenital system (UGS) development with an UGS specific Cre line Pax 8 Cre. Pax8 Credeletion was expected to recombine the floxed genome in the nephronprecursors, ureteric bud and the Wolffian duct derivatives. In crossesbetween Fgf8 c/c and Fgf8 n/+ ; Pax8 Cre mouse lines Fgf8 gene was deleted successfully. As a result the whole UGSwas affected. The kidney was severely reduced in size. Newborn nullmice were born alive but died within 24 hours likely due to kidneyfailure. In the deficient kidney the organization of theproximal-intermediate segments of the developing nephron was disturbed. Marker analysis with in situ hybridization was consistentwith serious defects in nephrogenesis. We conclude that Fgf8 functionis involved in the control of Wolffian duct development andsegmentation of the assembling nephron. The Zellwegerspectrum disorders (ZSDs) are characterized by a generalized loss of peroxisomal functions caused by deficient peroxisomal assembly. Clinical presentation and survival are heterogeneous. Although most peroxisomal enzymes are unstable in the cytosol of peroxisomedeficient cells of ZSD patients, a few enzymes remain stable among which alanine: glyoxylate aminotransferase (AGT). Its deficiency causes primary hyperoxaluria type 1 (PH1, MIM 259900), aninborn error of glyoxylate metabolism characterized by hyperoxaluria, nephrocalcinosis, and renal insufficiency. Despite the normal level of AGTactivity in ZSD patients, hyperoxaluria has been reported in several ZSDpatients. We aimed to determine the prevalence of hyperoxaluria in ZSDs and tofind clinically relevant clues that correlate with the urinary oxalate load. Methods: We reviewed medical charts of 31 Dutch ZSD patients with prolonged survival (>one year). Results: Urinary oxalate excretion was assessed in 23 and glycolate in 22 patients. Hyperoxaluriawas present in 19 (83%), and hyperglycolic aciduria in 14 (64%). Renal involvement with urolithiasis and nephrocalcinosis was present in five of whichone developed end-stage renal disease. The presence of hyperoxaluria, potentially leading to severe renal involvement, was statistically significant correlated with the severity of neurological dysfunction. Discussion: ZSD patients should be screened by urinalysis for hyperoxaluria and renal ultrasound for nephrocalcinosis in order to take timely measures to preventrenal insufficiency. Menkes disease is a very rare x-linked recessivedisorder of copper metabolism. The frequency is 1: 250.000 live births. Mutations in the ATP7A gene are described, which encodes for aintracellular copper-binding membrane protein. Pathogenetically a defect in copper absorption is responsible for inadequate synthesis of copper requiringenzymes and causes multisystemic manifestations. The clinical picture ischaracterized by early neurodegenerative symptoms like muscular hypotony andcerebral seizures. The patients also present with the so called kinky hair, hyperelastic skin, and anomalies of the kidneys and the urinary tract. Wereport on a patient of non consanguineous parents of German origin. Theprenatal ultrasound did not show any malformations. Birth at 35 weeks ofgestation. Postnatally a softening of the cranial bones and a vesicoureteralreflux IV° with dilatation of the renal pelvis combined with a subpelvicureteral stenosis had been observed, which were operated at the 2 nd month of life. At the age of 3 months the patient presented with seizuresand abnormal hair structure. Within the diagnostic course Menkes diseasehas been suspected and the nonsense mutation pArg980X has been identified inthe ATP7A gene. The mother is not a conductor, a mutation in thegermline cannot be excluded. Conclusion: The combination of urinary tract malformations and neurodegenerative symptoms should let you think of the very rare Menkes disease. Introduction: Primary Hyperoxaluria Type 1 (PH1) is an inborn error of glyoxylate metabolism due to the deficient activity of the hepatic peroxisomal enzyme AGT (alanine: glyoxylate aminotransferase). It leads to excessive endogenous oxalate production. Patients develop urolithiasis and renal insufficiency. The contribution of specific precursors in the pathway leading to endogenous oxalate synthesis is not known. This is warranted to design appropriate treatments. We aimed to test the contribution of different precursors to oxalate synthesis. Methods: Wild type mouse hepatocytes were incubated with different potential precursors of glyoxylate, either in the presence or absence of alanine. In the absence of alanine flux through AGT is deficient thereby mimicking AGT deficiency. Similar experiments were also performed in hepatocytes from AGTdeficient mice. Results: Oxalate production was found to be highest with glyoxylate as substrate in the absence of alanine, whereas oxalate production was lower with glycolate, hydroxypyruvate, glycine, fructose, and ethylene glycol. The results obtained in wild-type hepatocytes incubated in the absence of alanine were comparable to those obtained in hepatocytes from AGT-deficient mice. Upon addition of alanine to wild-type mouse hepatocytes, however, resulted in 30% lower rates of oxalate production, in contrast to hepatocytes from AGT deficient mice. Discussion: Hepatocytes derived from AGT deficient mice represent a good model to study the contribution of different precursors to oxalate production in PH1.

S. Grisaru 1 , C. Geary-Joo 2 , F. Snider 2 , J. Cross 2 1 University of Calgary, Department of Pediatrics, Calgary, Canada 2 University of Calgary, Department of Biochemistry and Molecular Biology, Calgary, Canada Gcm1 (Glial Cell Missing), is a transcription factor necessary for the formation of placental syncytiotrophoblast in mice. Gcm1 mutant mice die before nephrogenesis at embryonic day (E) 10. During early murine development Gcm1 expression is limited to the placenta. However, immediately after birth, Gcm1 is increasingly expressed in the kidney in proximal tubular cells in the outer medulla. We recently reported successful rescue the GCM1 null phenotype using a tetraploid aggregation approach (JASN Vol.17, 2006) . Since our previous report, further analysis of the aggregation products confirmed only 3 homozygous mutants (2 males and a female) obtained from six hundred and twenty five transferred aggregate embryos resulting in 121 live pups. Abnormal cortico-medullary patterning was demonstrated by histology analysis of adult GCM1 null mice kidneys. This abnormality was further defined by immunohystochemical detection of known nephron segment-specific markers (aquaporin-7, aquaporin-2 and Tamm-Horsfall protein) in GCM1 null kidney sections. To define the expression of GCM1 in human kidneys, commercially available anti-human GCM1 polyclonal antibodies were used to detect GCM1 protein in tissue sections of newborn kidneys obtained from autopsies. GCM1 was detected by immunohystochemistry in the renal cortex in tubular structures with cells having a brush border suggestive of proximal tubules. GCM1 signal was not detected in the renal medulla. Conclusion: In humans, Gcm1 is expressed in renal proximal tubules at birth whereas in adult mice its mutation is associated with abnormal renal cortico-medullary ultrastructure. This effect may represent a primary role for GCM1 in late renal development and patterning, or structural changes occurring postnatally secondary to alterations of tubular physiology caused by GCM1 inactivation. Objectives: Lupus nephritis (LN) in Singapore children treated with cyclophosphamide and/or azathioprine has a poor prognosis with a reported 10-year renal survival of 59%. This study examined the long-term outcome of children with lupus nephritis using a new protocol comprising pulse intravenous methylprednisolone, MMF ± cyclosporine. Method: Twenty-one children with LN (age range at start of treatment 3.7-14.8 years) who were treated between the years 1995 to 2007 were included in this retrospective study. MMF dose was 1200 mg/m 2 /day. Mean duration of follow-up was 3.6±2.0 (range 1.3-8.6) years. Treatment outcome was defined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), renal function, proteinuria and serologic markers. Effect of steroids on growth was assessed by height standard deviation score (HtSDS). Statistical analysis was performed using Wilcoxon signed rank test. Results: At presentation, 72% had nephritic-nephrotic syndrome, 14% had nephrotic syndrome, while 14% had renal failure requiring dialysis. Renal biopsy classification (WHO) was II in 19%, III in 24%, IV in 33%, and V in 24%. Comparing pre-MMF treatment and current follow-up parameters respectively, SLEDAI (17.4±8. Objectives of study: To understand the effects of response gene to complement 32 (RGC-32) in TGF-β1 induced epithelial-mesenchymal transition (EMT) on human renal proximal tubular epithelial cells (hPTECs). Methods: Constructed RGC-32 expression plasmids and RGC-32 siRNA hairpin plasmids, transient transfected them into hPTECs in vitro, and then treated hPTECs with TGF-β1 (5ng/ml) or vehicle alone for indicated time (0, 30min, 2h, 8h, 24 h) . RT-PCR and Western Blot were used to determine the expression of a-SMA, ECM (Col-I, FN1). The mRNA expressions of E-Cadherin and SM22a were detected by RT-PCR. Results: (1) The promoting effects of RGC-32 on EMT. Instead of stimulation with TGF-β1, the hPTECs, those overexpressed RGC-32 gene, de novo obtain the ability to produce markers of myofibroblast phenotype (a-SMA, COL-I and FN) and SM22a gene, as well as lost the capability of expressing E-Cadherin gene. (2) The eliminating effects of RGC-32 siRNA on EMT that induced by TGF-β1. After stimulation of TGF-β1 for 24 hours, the expression of a-SMA, COL-I, and FN as well as SM22a gene in hPTECs, those RGC-32 genes were interfered with RGC-32 siRNA, were significantly decreased than that in controls. Conclusions: RGC-32 was an important regulator for TGF-β1 and its downstream signalling Smad proteins on EMT.

Background: Low birth weight is associated with a low nephron endowment. This may predispose to hyperfiltration and cascading proteinuria particularly if obesity develops. Our report relates to an emerging population of children with proteinuric kidney disease in our multiethnic community. Methods: Forty-two obese children (mean age 14±5 years) with proteinuric kidney disease (KD) were studied. Twenty-four were of normal birth weight (NBW>3000 grams) and 18 were of low birth weight (LBW<1200 grams). There was a female (24/42=57%) and an ethnic predominance (23 African, 16 Hispanic). Degree of proteinuria was determined by the random urine protein (pr) and albumin (alb) to creatinine (cr) ratios (Upr/cr and Ualb/cr). Renal function (eGFR) was estimated from the Schwartz formula. Body mass index was used as a measure of obesity (>95% centile). Insulin resistance was measured by the homeostatic model assessment (HOMA). Kidney tissue was obtained in 28 of the patients for pathology and histomorphometry. Results: Average BMI was 96±4% tile. Fasting insulin and HOMA scores were not significantly different in the obese NBW versus obese LBW children. Renal biopsy specimens revealed focal glomerulosclerosis (FSGS) in the majority of patients (23/28=83%). Progression to end stage kidney disease was significantly greater in LBW compared to NBW children with a median renal survival of 11 years, p<0.01. Glomerulomegaly as measured by glomerular diameter was similar in obese patients and significantly greater than non-obese controls with FSGS.

Conclusions: Obesity appears to be a confounding factor in the development of glomerulosclerosis and progression of kidney disease in children. Low birth weight and concomitant low nephron endowment may contribute to disease progression, especially in those of African and Hispanic descent.

Objective: to determine long term outcome and prognostic factors of IgA nephropathy in a large single center cohort of pediatric patients. Patients and methods: we have reviewed the medical charts of 79 patients with biopsy proven IgAN that have been followed at our institution from 1983 to 2004, with a minimal follow-up of 2 years. Follow-up data, including proteinuria >500 mg/24 h or the need for ACE-Is therapy, chronic renal failure (CRF) and hypertension were analysed after 2 years and 5 years of follow-up. Data from 60 patients with follow-up longer than 5 years were also available (mean follow-up 9.9 years, range 5-24 years). 61% of patients received therapy (cyclophosphamide in 10 patients and/or steroid±ACE-Is in the remaining). Clinical features at the onset, histology class (Lee and Haas) and treatment during the first 2 years were analysed by multivariate analysis against the above mentioned dependet variables. Results: the average follow-up was 7.85 years (range 1-24 years). Presentation symptoms included macroscopic hematuria in 76% of patients. At the end of follow-up, renal function was normal in 94% patients, 3 patients have reached end-stage renal disease and 2 had chronic renal failure. Proteinuria or the need for ACEIs at 2 years was significantly associated with the age of onset (OR: 1.30 [1.09-1.56] ) and proteinuria at the onset (OR: 1.86 [1.05-3.32] ). CRF was significantly associated with familial IgAN (OR>10). Hypertension at onset was significantly associated with persistent hypertension during follow-up (OR: 8.82 [1.55-50] . Conclusion: taken together, these data indicate that the overall prognosis of IgAN is good during childhood and that the worst prognostic factor for development of CRF is familial IgAN. Overall, histological classification had a poor correlation with the outcome of the disease. This study was designed to compare three urinary protein expert systems for profiling proteinuria (PU) in children with kidney diseases. Freshly voided urine was collected from 61 children with glomerular diseases, 19 children with tubular diseases and 25 healthy children aged 3-16 years. 23 out of 80 children with renal disease had a glomerular filtration rate (GFR) <90 ml/min/1.73 m 2 . The urinary protein expert systems were 1. albumin/total protein ratio (APR), 2. alpha-1microglobulin/alpha-1-microglobulin + albumin algorithm (AAA), and 3. the complex UPES algorhithm (using serum creatinine, urinary total protein, alpha-1-microglobulin, albumin, IgG, alpha-2-macroglobulin and dipsticks). APR correctly identified glomerular PU in 47 of 61 (77%) children with glomerular diseases, tubular PU in 16 of 19 (84%) children with tubular diseases and normal PU in 23 of 25 (92%) healthy children. AAA correctly identified glomerular PU in all 61 (100%) children, tubular PU in 18 of 19 (95%) children, and all 25 healthy children were characterized as having no pathological PU. UPES differentiated the type of PU in children with glomerular diseases into glomerular (50/61 patients) and mixed glomerulo-tubular (6/61 patients). Tubular PU in children with partial or complete renal Fanconi syndrome was identified in 16/19 patients and described as mixed glomerulo-tubular PU in 3/19 patients. Mixed glomerulo-tubular PU was only found in children with CKD stages 2-5 of glomerular and tubular diseases. In conclusion, urinary protein expert systems may be used to distinguish between glomerular and tubular PU. The AAA algorithm had the highest reliability when compared with the two other expert systems and the accuracy was not negatively influenced by a decrease of GFR. However, UPES provided additional information on mixed glomerulo-tubular PU in patients with a low GFR. Background: The three LMW proteins Cystatin C (Cys), β2-Microglobulin (β2-M) and β-Trace Protein (β-TP) are useful markers of GFR. Cys is particularly well suited for the detection of incipient renal failure. However, corticosteroid medication has been shown to stimulate Cys production. Aim of the study: Analysis of the effect of corticosteroid therapy on the correlation between GFR and the three LMW markers. Patients: 119 patients (47 f, 72 m; median age 10.9 years, range 0.2 to 18.9) with malignant (n=47) or nephrological (n=72) diseases underwent a single-shot inulin clearance. The respective LMW proteins were measured by particle-enhanced immuno-nephelometry. 27 children received corticosteroids (prednisone or dexamethasone) in a mean dosage of 28 mg/m 2 /d of prednisone equivalent (Pred/BSA). Multiple linear regression analysis was performed between the LMW markers as dependent and both GFR and steroid-dose as independent variables. Results: Mean GFR was 77.2±27 ml/min/1.73 m 2 , mean Cys 1.08±0.5 mg/l, β2-M 2.17±1.33 mg/l and β-TP 0.97±0.57 mg/l. Cys was highly correlated with the reciprocal of GFR (p<0.0001) but not with corticosteroid-dose (p=0.138), whereas both β2-M and β-TP were highly correlated (p<0.0001) with both the reciprocal of GFR and the reciprocal of Pred/BSA. Discussion: Using gold-standard GFR measurements, we cannot confirm earlier reports indicating an increase in serum Cys during corticosteroid medication. By contrast, steroids significantly lowered both β2-M and β-TP serum concentrations. We conclude that at least in patients with mild renal insufficiency Cys -unlike β2-M and β-TP -appropriately reflects GFR also during steroid therapy. This further supports the concept of Cys being a superior marker of incipient renal failure.

Objective: To repeatedly follow kidney function since onset of type1diabetes and evaluate whether GFR can predict development of micro-or macroalbuminuria or end stage renal disease. Design: Observational Cohort Study. Methods: Since 1978, all diabetic patients undergo renal function tests every 2nd to 3rd year from onset. 363 children, 204 boys, have done 1640 clearance studies. 81 healthy children and young adults, 5-30 years of age, served as controls. GFR was evaluated by clearance of inulin during water diuresis and continuous infusion. Results: GFR during the first 15 years after onset of diabetes was significantly higher than that of controls (mean 130-142 vs. 116 ml/min/1.73 m 2 ). At onset, 2 and 5 years after, boys had significantly higher GFR than girls (mean 135, 148, 146 vs. 128, 134, 133 ml/min per 1.73 m 2 ) but after 8 years no differences were found between sexes. The occurrence of microalbuminuria, albuminuria during the first 15-20 years was analysed and mean of GFR of 0, 2 and 5 years, 2 and 5 years, 2, 5 and 8 years and all those GFRs separately were compared between patients still normoalbuminuric, microalbuminuric and macroalbuminuric after 10 and 20 years resp. No significant differences were found between the groups. Moreover the change in GFR from 0 to 5, 2 to 5 and 2 to 10 and 5 to 10 years were also compared between the groups and no significant differences were found.8 young adults reached end stage renal disease (ESRD) after 15-29 (median 20) years and comparing their GFRs during the first 5-8 years with those still normoalbuminuric after 20 years, no significant difference was found. Conclusions: Hyperfiltration is found in children with type 1 diabetes during the first 12-15 years from onset and hyperfiltration was equally seen during the first 5-8 years in those children who in the future developed normo-, micro-, albuminuria and/or ESRD. Background: HIV Associated Nephropathy (HIVAN) remains an important entity despite the use of highly active anti-retroviral therapy (HAART). Our objectives were to determine the prevalence and severity of renal manifestations in a cohort of HIV infected children during the HAART era. Methods: A retrospective analysis was conducted on 286 children infected with HIV. Renal assessments included quantitation of proteinuria, radiologic abnormalities, and renal function. Persistent Proteinuria (PP) was defined by urine protein to creatinine ratio (Upr/cr) >0.2 detected on at least two measurements 1 month apart. Renal sonography and MAG 3 renal scintigraphy were categorized according to the presence of bilateral increased echogenicity and/or nephromegaly, and cortical retention and/or diffuse parenchymal disease, respectively. HIVAN was considered in those children that had PP associated with any radiological abnormalities. Results: Of the 286 children, 98.6% were perinatally infected. Eighty-five (29.7%) had PP. Of these, 46 had PP alone, while 39 (13.6%) developed HIVAN. The mean age of onset of HIVAN was 9.4±0.8 years. Overall mortality at the time of analysis was 3.8% and it was highest in those with HIVAN. Viral load (VL) >100, 000 copies was significantly associated with HIVAN. Creatinine clearance was significantly decreased in patients with HIVAN. Conclusions: The prevalence of PP in our population of perinatally infected children remains high (29.7%), with at least half of them showing evidence of HIVAN. Persistently high VL (>100, 000 copies) was associated with the presence of HIVAN. A spectrum of renal related disorders is a frequent occurrence in HIV infected children and should be sought with periodic urinalysis, quantitation of proteinuria and renal function, and imaging and/or histopathological studies. MMF has shown to be effective in adult LN, whereas only anectodical data are reported in childhood. We evaluated MMF in 15 children with LN, 11 F/4 M, mean age: 12.4±3.9 yrs, proteinuria >3 g/day, decreased C3 and increased anti-dsDNA serum levels, normal renal function. Renal biopsies, before MMF, showed the following classes (Weening) : IV in 8 cases, III in 1, II in 5, VI in 1. Before MMF: 2 patients have received i. v. CyP; 2 more received AZA and CsA but were in flare-up of disease; the remaining 11 were newly diagnosed patients. Each patient received three i. v. Metilprednisolone pulses and thereafter MMF (plus oral Prednisone(P): 1 mg/kg/day) was administered (mean dose: 29±7.7 mg/kg/day; through level: 3.6±1.2 μg/ml). Outcome was monitored by SLEDAI score, renal function, proteinuria. In 11 children P was tapered and, after 4.6±2.3 month mean time, stopped; 4 children were receiving P (0.3 mg/kg/day). The mean followup is 35±16 months. Sustained clinical remission was observed: proteinuria was absent in all, in 10 patients an increase of serum C3 and C4 and a decrease of anti-dsDNA levels was seen. Significant steroid sparing effect was obtained: hypercorticysm dramatically improved. Of the 15 patients 8 achieved 2 years of MMF treatment and in them, at this time, a serial second renal biopsy was performed: histopathological activity indices reduced (8.76±2.55 vs. 5.3±6.97, p<0.01), whereas chronicity indices did not change (3.47±1.56 vs. 3.3±3.31). No haematological and/or gastrointestinal side effects were observed. Our pilot study suggests that MMF represents a good alternative to traditional therapy in the treatment of SLE in children, and in controlling disease activity and as steroid sparing agent without significant side effects over the entire period of therapy. MMF has shown to be effective, during treatment, in mantaining remission of childhood SD and CSAD NS, but few data are available on the MMF long term effectiveness after drug stopping. We report the results of two years MMF treatment in 33 children with SD and CSAD NS. The characteristics of SD and CSAD groups were, respectively: 19 patients, 11 boys, mean age 6.7 yrs vs. 14 pts, 11 boys, mean age: 11.6 yrs (p<0.005); first episode NS mean age: 3.4 yrs vs. 6.3 yrs; NS mean duration: 2.9 yrs vs. 7.4 yrs (p<0.001); mean steroid therapy duration: 2.2 yrs vs. mean CsA therapy duration: 3.2 yrs; histologic features: FSGS 2, MC 17 vs. FSGS 9, MC 5. In both groups MMF was started after remission was achieved with Prednisone administered at the last relapse. MMF treatment: Lenght: 24 months; Mean Dose: 27.8±4, 1 mg/kg/day; plasma Through Level: 3.6±1.2 mcg/ml; Non Responder: patient presenting a NS relapse during MMF. In SD group 17(83%) and in CSAD 12 (85%) subjects were responders. In 14 patients of SD group and 10 patients of CSAD group P could be withdrawn over a mean period of 11.3 months, so that NS remission was sustained just by MMF; remaining patients were receiving P at a mean dose of 0.3 mg/kg/a. d. Two years MMF treatment was accomplished in 26/33 (78%) patients. At 24.3±5 months mean followup since MMF withdrawal, 6 (23%) patients (4 of SD and 2 of CSAD group) relapsed after 9.3 months (3.2-12.1) mean time No haematological or gastrointestinal side effects were observed. Our results demonstrate that two years MMF treatment in SD and CSAD NS children is effective not only in maintaining remission during therapy, but also in achieving persistent remission after withdrawal of drug in a significant rate (>70%) of patients; the side effects and the rate of MMF dependence are negligible with respect to those of Steroids and CSA. Information on long-term renal function following treatment for Wilms tumor (WT) are relatively scanty. Previous studies reported a worrying late development of microalbuminuria (uMA), hypertension (HPT) and even reduction in glomerular filtration rate (GFR). The aim of the present study was to evaluate the long-term renal outcome in a cohort of patients who underwent uninephrectomy for WT. Glomerular function (as creatinine clearance by Cockroft-Gault formula) was calculated and uMA (as uMA/uCr ratio) as well as urinary b 2 Microglobulin excretion were detected. 24-hours ambulatory blood pressure monitoring was also recorded. Fifteen patients (11 F) with a median age at WT diagnosis of 4.4 yrs (range 1.8-16.6) were studied. The median follow-up was 13.3 yrs (10.2±19.3). Eight patients had been classified as WT stage 1 and 7 as WT stage II. All patients had been treated with unilateral total nephrectomy and chemotherapy. Two of the children had also been addressed to radiotherapy. The primary disease did not recur in any of the patients. The median age at time of investigation was 18, 3 yrs (range: 12, 7-30, 4). None of them had a GFR below normal limit (mean GFR was 109.8±26.8 ml/min/1.73 m 2 ). Urinary b 2 Microglobulin excretion was normal (mean ub 2 /uCr: 0.5±0.3) in all of the patients. The mean uMA/uCr ratio, was 0.13±0, 1 with only 1 patient exhibiting higher then normal values (uMA/uCr ratio: 5, 3). The 24 hr blood pressure was normal in all patients with a mean systolic and diastolic blood pressure SDS of -0.5±0.7 and -0.1±0.8, respectively. We conclude that as far as renal function, unilateral total nephrectomy combined with chemotherapy for low-stages WT can be look at as a safe treatment although it might be wise to monitor renal function at 5-year interval. Classicaly, patients are divided into monosymptmatic enuresis (MNE) and non-monosymptomatic enuresis, however, there is upcoming evidence that this subtyping might be artificial. The aim was to register the characteristics of nocturnal diuresis-rate and bladder volume in both subtypes. Methods: Retrospective analysis of 1000 consecutive patient-files, age 6-18, primary consulting for enuresis in a tertiary center. Registration of Incontinentia diurna (ID) and maximal functional bladder volume (Vmax), 24 hours urine-collections in 4 day and 4 nighttime-collections with Uosmol and diuresis-volume (DV) and-rate. Patients are divided into a MNE and NMNE-group. Results: 1) Vmax is significantly lower than bladder volume for age, 2) Nocturnal polyuria is only present in 1/3 patients, 3) Nocturnal diuresis is >Vmax, 4) There is a significant linear correlation between ND and the nocturnal/daytime-diuresis-ratio, indicating fluid intake dependency. 5) There is a negative correlation between ND and urinary osmolality. 6) But the positive correlation between total nocturnal osmotic excretion and ND is much stronger. This unexpected observation cannot be explained by the classical primary vasopressin-theory. Conclusion: Our data show (almost) no statistical difference between the MNE and NME-groups, suggesting a continuum instead of 2 separate identities. Both groups have a significant low Vmax and nocturnal polyuria. The observation of the extremely strong correlation of nocturnal polyuria with the high osmotic excretion and high 24 h urine-production suggests that nocturnal diuresis-rate is highly fluid-and nutrition-dependent, and therefore more attention should be given to this part of the urotherapy.

A. Deguchtenaere, A. Raes, J. Dehoorne, R. Mauel, E. Vanlaecke, P. Hoebeke, J. Vande Walle

There is increasing evidence that a subgroup of patients with nocturnal polyuria may have an abnormal circadian rhythm of tubular sodium which may result in vasopressin resistance. The pathogenesis of this phenomenon remains to be elucidated. However if the increased sodiumexcretion overnight results in the dDAVP-resistance, decrease of the sodium-excretion-overnight may respond in subsequent dDAVP response. Aim of the study: retrospective study on the circadian rhytm of diuresis-rate and osmotic excretion in basal condition and subsequent during introduction of dDAVP, diet and furosemide. Results + discussion: 1) Baseline-values show significant lower Uosmol and higher diuresis-rate overnight compared to controls. Striking is the >40% part of electrolytes to explain the high osmotic excretion. 2) introduction of Ddavp results in a normalization of nocturnal Uosmol, but despite a significant decrease of Uosmol overnight, nocturnal polyuria persists.

3) Protein-and sodium-restriction results only in slight differences, but of course we do not have data on the compliance. 4) Furosemide in the morning results in a significant increase of daytime diuresis, osmotic and sodium-excretion, but as compensation decreased nighttime diuresis, osmotic and sodiumexcretion. 5) In 8/10 cases the antidiuretic effect results in an anti-enuretic effect. Conclusion: This pilot study clearly demonstrates that introduction of early morning furosemide results in significantly lower nocturnal diuresis. Because the urinary osmolality remains high, this correlates with decreased nocturnal osmotic excretion associated with increased osmotic excretion (sodium) during daytime. Background: The elasticity of the vessel walls decreases with age, this process is dramatically speeded up by uremia. As an early indicator of arteriosclerosis pulse wave velocity (PWV) increases along with arterial stiffness. Aim: to establish normal values for PWV in healthy children; to compare it with children on dialysis. Patients, methods: PWV was measured with a PulsePen device in 116 healthy children and young adults (age range 6-23 years) as well as in 10 uremic children (14,4±4 years) (CRF) treated by hemodialysis (n=7) or peritoneal dialysis (n=3). Two control groups of 10-10 childrens were formed using the database of healthy children: one matched for age (A-C) and one adjusted for height and weight (H/W-C). Blood pressure, heart rate, serum calcium (Ca), phosphate (P) , and parathyroid hormone levels were also determined. Results: a significant linear correlation was found between PWV and age (R=0, 60), height (R=0, 49), weight (R=0, 43), (p<0, 01), systolic blood pressure (r=0, 38) and heart rate (r=-0, 24) (p<0, 05). CRF patients were smaller by 15, 3 cm than A-C (p<0, 05), and younger than H/W-C by 4, 5 years (p<0, 01). PWV in CRF (5, 68±0, 96 m/s) did not differ significantly from A-C (5, 04±1, 18), however it was elevated in comparison to H/W-C (4, 51±0, 55 p<0, 01). Serum P, CaxP and PTH was increased in CRF (P<0, 001) Conclusion PWV is higher in children with CRF as a sign of increased arterial stiffness. Controls matched for height and weight should be used in states of severe growth retardation. A number of established risk factors potentially responsible for arterial dysfunction are present in CRF. NGAL has been identified as an early marker of acute renal failure (ARF). Sepsis in very low birth weight (VLBW) infants is associated with ARF more often than recognized. The aim of this study is to determine whether NGAL represents a marker of renal impairment in VLBW infants affected by sepsis. Samples of urine of 36 VLBW infants were prospectively collected for weekly measurement of NGAL. After evaluation of the clinical course, 2 groups were identified: group sepsis includes 14 infants affected with 16 septic events associated with some degree of renal impairment and group normal includes 22 uncomplicated VLBW infants. A mouse model of sepsis was created in 11 neonatal mice by intra-peritoneal introduction of Salmonella lipopolysaccharide. Kidneys were harvested 24 hours after the challenge, and NGAL mRNA was quantified by real time PCR. NGAL values of the normal group did not differ with gestational age or post-natal age of the neonates. The upper bound of the 95th percentile confidence interval was 40 ng/ml. The median value of NGAL in the sepsis group at 7 days before the septic event was 75 ng/ml and during sepsis was 150 ng/ml: these values were not significantly different, but both were significantly higher (p<0.001) than the median of the normal group (10 ng/ml). Once sepsis had been treated, the median value of urinary NGAL was similar to normal (10 ng/ml p=0.17). Changes in urine NGAL concentration paralleled changes in serum creatinine. Sepsis induced animal models showed a dramatic increase of NGAL mRNA in kidney tubules that paralleled acute renal failure. These neonatal animal and human data suggest that NGAL may be an early marker of renal impairment in septic VLBW babies. Further investigation is necessary to more exactly define the temporal relationship between the onset of sepsis/ARF and rise in urine NGAL concentration. We report 4 cases of acute renal failure (ARF) associated with orellanus syndrome, a cortinarius mushroom poisoning. Grand-father, mother, father and son presented with ARF 1 week after gastrointestinal symptoms and 2 weeks after repetitive ingestion of wild mushrooms. Critically ARF was observed for the 11 year-old boy: anuria, severe metabolic disorders (hyponatremia 124 mmol/l, hyperkaliemia 9 mmol/l, serum creatinine 1137 mmol/l, blood urea 54 mmol/l). Renal biopsy was performed for the grand-father, father and son (day 6, 9 and 8 respectively after presentation) and showed similar lesions: severe tubulointerstitial nephritis (TIN) with tubular necrosis and interstitial fibrosis. Renal replacement therapy was necessary for the father and the son. The mother recovered completely in two weeks without dialysis while renal function improved slowly for the two men. The boy is still hemodialyzed 5 months later. His main problem is uncontrolled hypertension. The diagnosis was confirmed 3 weeks later since fungal spores of cortinarius orellanoides were observed in the contaminated meal by light microscopy. The severity of the disease seems to be related to the toxin quantity: the 40kg boy ate mushrooms as much as his father and grand-father, the mother ate much less. Cortinarius spp poisoning is an exceptional paediatric cause of ARF. Gastrointestinal disorders are the main symptoms of the initial phase of the poisoning appearing 3 days after the mushrooms ingestion. The renal phase is delayed (median 8.5 days) characterized by ARF secondary to TIN. The toxin effects are dose-related, explaining the severity of the boy's symptoms. The prognosis is severe with 60% of end stage renal failure. Currently no treatment is available. Although rare, mushroom poisoning should be considered in the differential diagnoses of ARF with TIN.

L. Mendels, AH. Bouts, J-C. Davin, J. Groothoff Emma Children's Hospital/Academic Medical Center, Pediatric Nephrology, Amsterdam, the Netherlands Background: Inchronic dialysis, Tertiary Hyperparathyroidism (TH) is clinically revealed by persistent combined high parathyroid hormone (PTH), normalor high total serum calcium (tCa) and normal phosphate levels. Sincethe introduction of bicarbonate containing dialysate in peritoneal dialysis (PD), we have observed combined high tCa and PTH level sunusually early after onset of dialysis therapy. In most of the secases, ionized Calcium (iCa) levels were low. We aimed to investigate the extent of this discrepancy and its association with the mode of therapy. Methods: Serum iCa, tCa, PTH, bicarbonate and capillary pH were assessed over 2 years in 10 pediatric PD, 11 hemodialysis (HD) and in 9 transplanted (Tx) patients. Associations between tCa, PTH and iCa were analyzed. Results: Comparedto Tx patients, we found in PD and HD patients a lower mean iCa/tCaratio (both p<0.0001), an increased mean tCa-iCa (p<0.001 and p <0.01, respectively), and a higher number of combined normal/increased tCa and decreased iCa and increased PTH values (44.7% and 32.3%, respectively for PD and HD, vs.0% for Tx). Alow iCa/tCa was associated with a high capillary pH (R=-0.51; p<0.0001), a high venous bicarbonate (R=-0.34, p=0.001) and a lowage (R=0.21, p=0.02). Conclusions: iCa levels are warranted for monitoring calcium phosphate homeostasis in dialysis patients, especially in young PD patients. The use of only tCa levels might lead to an inadequate treatment with Vitamin D, and henceinduce the development of autonomous hyperparathyroidism in these patients. Preterminal renal failure (PRF)and end-stage renal disease in children and adolescents are associatedwith an increased risk of atherosclerosis and cardiovascular disease. Oxidative stress is one of the pathogenetic factors that could possiblybe influenced by therapeutic interventions. We investigated biomarkers of oxidative stress in 12 children (median age 9.6 years) with PRF (median GFR 43 ml/min/1.73 m 2 , range 15-86) andin 11 children (median age 11.9 years) under peritoneal dialysis (PD)and 13 healthy age-matched controls (C). Plasma samples wereinvestigated for malondialdehyd (HPLC) and carbonyl groups in proteins(ELISA) as biomarkers for oxidative stress as well as the plasmaantioxidative substances vitamin C (photometric), vitamin E (HPLC), ubichinols (HPLC), sulfhydryl groups in proteins(photometric), erythrocyte resistance to radicals and the total radicaltrapping antioxidant capacity (TRAP). In both patient groups PRF and PDwe found a depletion of sulfydryl groups and ubichinol-10 and a reducedresistance of erythrocytes to radicals. Malondialydehyd (p<0.05) andcarbonyl groups (p<0.01) were elevated in the PD group compared tocontrols. Conclusion: From these studies we concludethat in children under peritoneal dialysis biomarkers of oxidativestress are elevated. Moreover antioxidative defenses in preterminalrenal failure as well as under peritoneal dialysis are impaired.

Significant Acute Renal Failure due to Non-Steroidal Anti-Inflammatory Drugs: Inpatient Setting

In United States non-steroidal anti-inflammatory drugs (NSAID) are freely available over-the counter. Many children routinely use them without medical supervision. Fourteen inpatients mean age of 15.0±2.84 years (4 males, 10 females), were referred to nephrology for acute renal failure. Based on history, biochemistry, imaging and urinalysis the diagnosis of acute renal failure due to NSAID was made. All patients admitted to taking ibuprofen and six also consumed naproxen. The exact doses of either could not be scientifically determined as none were prescribed by a physician. None of the patients had underlying renal diseases at the time of admission. Nine patients had proteinuria and 12 had hematuria (including one with gross hematuria). One patient had nephrotic syndrome but resolved spontaneously without steroids and has remained in remission for 2 years. Two patients required dialysis. Only one of the dialyzed patient required steroid therapy for recovery of renal function. All data are expressed as mean±SD. The mean duration of hospitalization was 6±4.3 days. The mean serum creatinine at the peak of renal failure was 3.97±4.74 mg/dL (range 1.2-16.6). All patients recovered renal function with normalization of serum creatinine to 0.72±0.15 mg/dL (range 0.5-1, p<0.01). However, the duration from onset to normalization of serum creatinine was 48±63 days; indicating many patients had abnormal renal function for aprolonged period. In conclusion, NSAIDs pose significant risk of renal failure forsignificant duration and as an entity may be under recognized. Objectives: Treatment with growth hormone (GH) improves growth retardation of chronic renal failure. cDNA microarrays were used to investigate GH-induced modifications in gene expression in the growth plate of uremic young rats, the organ where longitudinal growth takes place. Methods: RNA was extracted from the tibial growth plate from two groups (n=10) of young rats: uremic (Nx) and uremic treated with 3.3 mg/kg/day of intraperitoneal GH for one week (NxGH). After reverse transcription, Agilent technology was used to analyze differential gene expression by microarrays containing 21, 000 rat probes (four hibridizations were performed). Most expressed genes were detected using linear models and Bayesian methods. To confirm gene expression changes shown by the chips, some genes known to play a physiological role in growth plate metabolism were analyzed by real-time quantitative polimerase chain reaction (QPCR). The ribosomal protein L4 (RPL4) expression did not show changes in the array and was used as the housekeeping gene. Results. GH modified the expression of 224 genes, 195 being upregulated and 29 down-regulated. The assay was validated by the QPCR results, which confirmed the sense of expression modification found in the arrays for insulin like growth factor I (down), insulin like growth factor II (up), collagen 5 alpha 1 (down) and proteoglican type 2 (up) . Conclusions: This study shows for the first time the profile of growth plate gene expression modifications caused by GH treatment in experimental uremia. The further analysis of selected individual genes, whose expression is differentially modified by GH will contribute to explain the mechanism of the stimulating effect of GH on growth in chronic renal failure. Objectives of study: Children with chronic renal failure have an increased risk of cardiovascular disease. This is associated with endothelial dysfunction, a key pathophysiological factor in atherosclerotic disease. Circulating endothelial progenitor cells (EPCs) have the potential to repair endothelial damage and promote angiogenesis. In adults, the number of EPC in peripheral blood correlates with endothelial function and reduced EPC levels are associated with a higher incidence of cardiovascular events. We aimed to investigate if children on long-term hemodialysis (HD) therapy have reduced EPC levels. Methods: We quantified circulating EPC in 12 pediatric HD patients before a midweek HD session and 11 healthy age-matched controls. EPC are a subfraction of the haematopoeietic stem cells (HSC) expressing both HSC-marker CD34 and the VEGF-receptor-2 KDR. Using flow cytometry, EPCs were identified as CD34+KDR+ cells and quantified relative to the number of granulocytes in the sample. Results: The number of EPCs in the peripheral blood was significantly reduced in HD patients (12.0±1.9 vs 29.0±7.3/10 5 granulocytes, 59% reduction; p=0.03). The total number of circulating HSC also tended to be lower in HD patients (71.2±7.3 vs 112.8±23.7/10 5 granulocytes, 39% reduction; p=0.09). Conclusion: The number of circulating EPCs is significantly reduced in children on long term HD. Reduced EPC levels may contribute to endothelial dysfunction and accelerated atherosclerosis in children on long term HD. Future studies are needed to identify the cause of this deficiency and to evaluate if increasing EPC levels provides therapeutic benefit. Objectives: Darbepoetin alfa (Aranesp ® ) is a novel erythropoiesis stimulating protein that has been shown in adult trials to have safety and tolerability equivalent to recombinant human erythropoietin. However, to date there is only limited published data on the use of Aranesp inpaediatric patients. The objective of this study was to determine the safety and efficacy of darbepoetin in children with chronic and endstage kidney disease. Methods: From 2003 to 2006, 30 children with either chronic or end stage kidney disease were enrolled in a prospective observational study. The initialdose of darbepoetin was 0.45 mcg/kg weekly (either IV or SC) and subsequent dose was titrated to achieve haemoglobin (Hb) between 110 and 130 g/dl. Results: Data analysis to date includes 22 patients (16 male : 6 female) whose agesranged from 1 month to 17 years (mean 9 years). Hb improved significantly with darbepoetin treatment from mean 84 g/dl (range 64-107) at start of treatment to 115 g/dl (range 81-147, p<0.001) at completion. The mean starting dose was 0.55 mcg/kg/week (range 0.4-0.9) which was not significantly different to the dose atthe end of the study (0.57 mc/kg/week, range 0.5-2.5). However, there was a significant change in the frequency of administration, with 85% commencing on weekly treatment, but only 25% still on weekly treatment at the end of the study (p<0.001). The most common treatment interval in stable patients was fortnightly (40%) but a significant number tolerated even longer intervals (25% dosed every 3 weeks or longer). Injection pain was common, but there were no other significant adverse events. Conclusions: Darbepoetin alfa is a safe and effective therapy for anaemia associated with kidney disease. The majority of children will maintain satisfactory haemoglobin at a dosing interval of every 2 weeks orgreater. High prevalence (43%) of left ventricular hypertrophy (LVH) and impaired systolic myocardial function in children with mild-to-moderate chronic renal failure (CRF) were observed in previous studies (JASN2006, JASN2007). In adult patients with uncomplicated arterial hypertension, LV mass (LVM) exceeding compensatory value for body size and cardiac workload (inappropriate or iLVM) is associated with poor prognosis, independently of LVH. We tested in CRF children if increased LVM compensates or exceeds the expected values for individual cardiac load and if iLVM is associated with impaired cardiac function. Complete anthropometrics, biochemical profile and Doppler echocardiograms were obtained in 24 children (age 11.5±5.2 yrs; GFR 48.7±30.3 ml/min/1.73 m 2 ). iLVM was defined above 109% of the value predicted for individual body size, gender, and stroke work and LVH was defined as LVM/m 2.7 >38 g/m 2.7 . 9 patients showed iLVM. Children with iLVM had higher mean age and lower heart rate as compared to patients with appropriate LVM (both p<0.05), without differences in blood pressure, BMI and GFR. After controlling for differences in age, gender distribution and presence of LVH, patients with iLVM showed similar cardiac geometry and diastolic function parameters compared to children with compensatory LVM (p=NS). In contrast, presence of iLVM was associated with lower LV ejection fraction (53.5±3.7% vs 63.0±3.6%) and lower midwall fractional shortening (15.9±1.8% vs 18.6±1.4%)compared to children with compensatory LVM (both p<0.01), indicating impaired LV chamber performance and reduced systolic myocardial function. In conclusion, in 37.5% of children with mild-to-moderate CRF, LVM is inappropriately increased for individual cardiac workload and body size. Presence of iLVM is associated with reduced systolic function, independently of age, gender and presence of LVH. pediatric nephrology centers were enrolled. Age groups of the patients were as follows: 41.9% newborn, 19.7% 2-12 months, 23.7% 13 months -10 years, 14.7% 11-18 years. Underlying diseases were prematurity (30.1%), malignancy (10.7), congenital heart diseases (CHD, 16.0), urologic disorders (7.3%). Low fluid intake was noticed in 35% of cases.50.4% of cases developed ARF after they have been hospitalized. Time to diagnose ARF was longer in the surgery department (4.32±5.01 days) compared to pediatrics (1.12±3.33 days), p<0.05. Thirty-nine percent of patients were on mechanical ventilation (MV) before the diagnosis of ARF, an additional 6.2% needed MVl after the diagnosis of ARF. ARF was prerenal, intrinsic and obstructive in 37%, 61% and 2% respectively. Hemodialysis and peritoneal dialysis was performed in 9.1% and 21.9% of cases. Mortality was 31.8%; and it was secondary to non-ARF related causes in 79.5% of cases; presence of MV, intrinsic ARF, prematurity, CHD, malignancy and being in intensive care unit were poor prognostic factors. Conclusion: Our nationwide data suggest that nephrologist, intensivist and pediatrician should focus on risk groups to prevent and to diagnose ARF earlier. Appropriate fluid intake and earlier consultation to a nephrologist are simple but may be effective measures to prevent ARF..

Hemolytic uremic syndrome is characterized by the triad of hemolytic anemia, acute renal failure, and thrombocytopenia. Recent studies have shown that Shiga-toxins (ST) may stimulate apoptotic cell death in renal tubular cells, but the underlying molecular mechanisms remain to be elucidated. In the present study, confluent LLC-PK1 cells were exposed to ST and cell death was studied with morphological and biological assay. In LLC-PK1 cells ST was found to induce apoptotic cell death in a dose-and time-dependent manner. The expression of calpain and Bax were significantly up regulated by ST, while the expression of Bcl-2 was down regulated. Cell death was completely inhibited by a specific Calpain inhibitor, but not by a broad caspase inhibitor, zVAD-fmk, implicating a caspase-independent pathway via calpain. Moreover, we found that serum factors could trigger a survival signal against ST-induced cell death through PI3K/Akt pathway. In conclusion, activation of calpain mediates ST-induced renal proximal tubular cell death, and the expression of Bcl-2 and Bax were oppositely altered. Stimulation of PI3k/Akt signalling protects cells against death.

Verocytotoxin (VT)-producing E. coli (VTEC) infection represents the main cause of Hemolytic Uremic Syndrome (HUS) in children. A nationwide surveillance system of HUS was introduced in Italy in May 1988 to follow the trend of VTEC infections. For each patient, epidemiological and clinical information was collected by a standardized questionnaire. Laboratory diagnosis of VTEC infection was based on the detection of VTEC and free VT in stools and of antibodies to the lipopolysaccharide (LPS) of serogroups, O26, O103, O111, O145, and O157 in the sera. The immuno-detection of VT on circulating neutrophils was also performed on some patients. As of December 2005, 481 cases have been notified, accounting for a mean annual incidence of 0.31x100,000 in the 0-14 age group with a significant difference among the regions (from 0.15 to 1.1); median age of patients: 23 months, 53% males. Most cases (53%) occured in summer from june to september. Seventy-nine per cent of the cases had prodromal symptoms such as bloody diarrhea (26%) and non-bloody diarrhea (51%). Five patients (1.0%) died from the disease. Stools and/or sera were collected from 380 cases. Evidence of VTEC infection was observed in 255 cases (67%). The VTEC serogroups most commonly detected were O157 (37% of the VTEC-positive patients), followed by O26, O145, O111 and O103. The number of cases associated with non-O157 infections increased over time: from 1997 the O26-associated cases are the most frequent. During the surveillance-period 4 epidemic clusters have been registered: 1992-Lombardia, 1995-Veneto, 1997 and 2005 Campania. The role of vesico-ureteral reflux (VUR) as a predisposition for acquired renal scarring with urinary tract infections (UTI) has been questioned in recent years. Few studies have investigated baseline factors associated with chronic nephropathy in severe reflux. We aimed to evaluate DMSA scans in children having any degree of primary VUR associated with UTI in order to identify variables that are predictors of the presence and/or development of renal scar. Data of patients with proven UTI who have primary VUR were evaluated retrospectively. Patients and renal units were classified as scar (+) and scar (-) by DMSA results. The following parameters were assessed with respect to their relation to presence of renal scarring: sex, age at diagnosis, grade (G) of reflux, number of subsequent UTIs (on new renal scars). There were 138 patients (M/F: 53/85, median age 42 months) and 212 refluxing units. Variables increasing the likelihood of scar detection were: male gender (32/53 vs. 35/85, p=0.043; OR 2.2), >26 months of age (for girls only; 31/59 vs. 4/26, p=0.003; OR 6.1), G IV-V reflux (OR 9.1 vs. G I-III reflux and 23.3 vs. no reflux). All boys having G IV-V reflux and girls over 26 months of age having G IV-V reflux had very high rate of scarring compared to the rest (21/23 vs. 46/115, p=0.0001, OR 15.8 and 14/16 vs. 53/122, p=0.002, OR 9.1, respectively). However, variables increasing the likelihood of new/progressive scar development were only the presence of previous scar (OR 8.3) and UTI number >1 (OR 3.0). Neither UTI number nor new/progressive scar development was affected by VUR grade. In conclusion, the most predictive variables for the presence of renal scarring among children presenting with a UTI were male gender, age (being >26 months; only for females) and grades IV-V reflux, while new/progressive scar development was associated with presence of previous scar and UTI number.

D. Hothi 1 , E. Harvey 1 , C. Goia 2 , D. Geary 1 1 Hospital for Sick Children, Department of Pediatric Nephrology, Toronto, Canada 2 Hospital for Sick Children, Educational, Toronto, Canada Introduction: adequate ultrafiltration (UF) is necessary for good health in dialysis dependent patients. However UF can be hindered by development of intradialytic symptoms and hypotension. Objectives: To determine whether sodium ramping, UF profiles and mannitol could improve UF without increasing intradialytic morbidity in children. Method: A standardized HD practice was instituted in our unit. We prospectively analysed 506 dialysis treatments from 11 chronic patients with routine scheduled HD, 4hrs x3-4/wk. Results: UF volumes between 3.2 to 9.7% of the dry weight were achieved. Mannitol reduced the risk of developing intradialytic symptoms by 64% (p<0.05) without altering the risk of hypotension, with a mean UF volume of 6.2% of the dry weight. A linear sodium ramp (148-138mmol/l) increased the odds of intradialytic symptoms (p=0.10) and hypotension (p<0.05), with no difference in the mean UF volume. All UF profiles increased the risk of intradialytic symptoms but the effect was not statistically significant except with profile 2 (stepwise reduction of UF during procedure). Achievement of dry weight was least likely with UF profile 2 (p<0.05); there was no statistical difference in the mean UF volume between them all. Conclusion: UF volumes higher than the traditional recommendations of 5% of the dry weight can be achieved in children. The use of mannitol increased the UF volumes and reduced symptoms without increased hypotensive episodes. Objective: Innate immunity and urinary tract response play a central role int he development of urinary tract infection (UTI), in which heat shock protein (HSP)70 and Toll-like receptor 4 have a key position. Patients and methods: HSPA1B A(1267)G and TLR4 A(896)G genotypes were determined using allele-specific polymerase chain reaction in 103 patients treated with recurrent urinary infection. Allelic prevalence was related to reference values of 235 healthy controls. Clinical data were also reviewed and statistically evaluated. Results: HSPA1B (1267)GG genotype and HSPA1B (1267)G allele occurred more frequently in UTI patients versus controls (p=0.0001) and both were associated with a higher risk of renal scarring (p=0.012 and 0.049, respectively). TLR4 (896)AG genotype and TLR4 (896) G allele had also higher prevalence among UTI patients than controls (p=0.031 and 0.041, respectively). The combination of carrying AG genotype at both sites meant the greatest risk for UTI (p=0.05). Conclusion: Our data indicate an association between the carrier status of HSPA1B (1267)G and TLR4 (896) One of the major goal of hemodialysis adequacy is to achieve the fixed endsession body weight, so called dry weight, in order to limit overhydration and thereby cardiovascular risks. The prescribedultrafiltration, can induce hypotensive episodes and thereby limit thedry weight achievement. On line equipments offer the assessment of theblood volume (BV) and its relative variation. The BV is derived fromdirect measurement of the hematocrite. Weroutinely use such an equipment (Fresenius A 2008 C) over all thesessions since February 2002, conducting to a clinical experience of 7800 BVM curves. These registered curves could be related to thehemodialysis prescription parameters (UF, NaD, TD, Kt/V) to the dryweight, the blood pressure and to the clinical dialytic symptoms. Thisexperience conducts us to define the normal BV curve over a sessionand its variations. Starting dialysis induces an acute initial (5 to 30 min) decrease of BV, 5 to 8%, mostly asymptomatic: extra corporeal circuit filling; this initialdecrease is a sign of normality. There after the normal BV curve should be flat; UF rate/amount being compensated by the plasma refilling rate: iso osmotic dialysis, no symptoms, no cramps, no hypotension, no vomiting. Incase of no BV decrease over the dialysis session, the patient isoverloaded: reduce his dry weight. In case of a decrease of the BVhigher than 10%, there is a hypotensive risk: UF rate/amount, dryweight, sodium dialysate, sodium temperature and Kt/V urea (cellular water shift) should be individually adapted conducting to arefilling curve. The effectiveness on the BV of these individual changein dialysis prescription can be directly, on line attested by the BVMcurve: plasma refilling capacity test. The BV changes reactivity is rapid, 5 to 15 min. Renalscarring following acute pyelonephritis (APN) in children is a frequentcomplication which may impair renal growth. Its pathophysiology includes host response, bacterial virulence, associated malformationand/or renal dysplasia. We prospectively studied virulence factors of E. coli isolates from children with a first episode of APN (fever >38.5 C°, CRP >20 mg/L, monomicrobial E. coli positive culture >10*5 cfu/mL). We excluded patients with anyconcomitant infection, renal dysplasia or obstructive uropathy (US examination, renal length <2 SD) or grade 4-5 VUR. Renal scarring was evaluated by DMSA scan performed 6 to 9 months after APN. 383 patients were included in a multicentre prospective randomized study comparing short vs long i. v. treatment with ceftriaxone as a first line antibiotic treatment [in press]; 161 out of them fulfilled criteria for virulencestudy. Six virulence genes were investigated by multiplex PCR (pap, sfa, afa adhesine genes; cnf1, hly toxin genes, aeraerobactin gene) and the K1 capsular antigen was researched by latextest. We identified 21 distinctive virulence profiles; 99% of E. coli strains had one or more virulence factors; 64% expressed the aer genewith at least one adhesin or one cytotoxic factor. Renal scars occurredin 18% of cases and low grade (1-2-3) VUR was detected in 46%. Statistical analysis did not show any correlation between the presenceof scars and E. coli virulence pattern. In addition, scarring was not correlated with the antibiotoc regimen but was correlated with grade 3 VUR (P 0.002). Most E. colistrains associated with APN in children show several virulence factors, mainly adhesins and cytotoxins, but their profile was not correlated with renal scarring. Background: Acute lobar nephronia (ALN), a severe renal parenchymal inflammatory disease, ranging between acute pyelonephritis (APN) and frank abscess formation, has been diagnosed with increasing frequency due to the advancement of non-invasive diagnostic modalities and the development of systematic diagnostic schemes. E. coli is the most common bacterialpathogen isolated from the urine samples of ALN patients and the associated percentage is significantly higher than those among the patients with first time urinary tract infections. This prospective study was conducted to elucidate and differentiate the bacterialvirulence factors associated with ALN and APN in pediatric patients. Methods: Patients included in the present study were those suspected of anupper UTI and underwent a systematic scheme of ultrasonographic, CT and Tc99m-DMSA evaluation for the differential diagnosis of ALN andAPN. Exclusion criteria were any evidence of underlying diseases orurinary anatomical anomalies except VUR. The E. coli isolates from the urine samples of patients were screened with PCR analysis for various urovirulence genes. Pulsed-field gelelectrophoresis was used to analyze the genetic association of theisolates. Results: A total of 88 patients were enroled. Forty-six patients were diagnosed as ALN, while the other 42 cases were APN. Diverse genotypes were found among the E. coli isolates in either group. Among the pathogenetic determinants examined, multivariate logistic regress analysis indicating that a papG II allele was the only significant urovirulence factor associated with ALN (p<0.005; odds ratio, 17.16). Conclusions: While no specific genetic lineage was identified among the E. coli isolates studied, a papGII gene was found strongly associated with the cause of ALN among pediatric patients without underlying disease other than VUR. 0-<21 yr during 1996-2005 were sent to leading paediatric nephrologists of 13 Asian countries/regions. Those having national renal registry were to use the registry data. Results: Data from 11 countries/regions were returned (incl. 3 national registries), namely China, Hong Kong SAR, India, Indonesia, Japan, Malaysia, Pakistan, Philippines, Singapore, South Korea & Thailand. A total of 2275 ESRD patients were reported: 772 on peritoneal dialysis (PD), 678 on haemodialysis (HD), & 825 transplant (TX) of 34%, 30% & 36% respectively. Chronic PD: CAPD and Automated PD (APD) were the main modes of PD at ratio of 2.6 to 1. Only 3 countries had APD morethan CAPD. Peritonitis rate ranged from 1 episode in 3 to 50 patient-months, and seemed less common in those having more APD. Chronic HD: HD comprised of 47% chronic dialysis, mostly adolescents. A-V fistula wasused in 76%, and permanent catheter 15% for vascular access. Background: Current data suggest the role of chronic inflammation and lipid disorders in atherogenesis. The aim of the study was to evaluate established and new markers of atherosclerosis in APD and HD pediatric patients and to assess whether the method of dialysis has an impact on those factors. Methods: Soluble(s) E-selectin, IL-4 and IL-12 concentrations were evaluated by ELISA in sera of 18 APD patients on, 9 HD patients and 15 controls. hsCRP levels were assessed by nephelometry. The lipid profile (total cholesterol (CHOL), HDL-CHOL, LDL-CHOL, triglycerides (TGL)) was also estimated. Results: sE-selectin concentrations in dialyzed patients were higher than in controls (APD p<0.0001; HD p<0.0001) and in APD were increased vs. HD (p<0.05). There were no differences in median values of IL-4, IL-12 and hsCRP between examined groups. CHOL levels were increased only in APD vs. controls (p<0.05). HDL-CHOL concentrations were decreased in all dialyzed patients when compared to controls (APD p<0.0001; HD p<0.01), without difference between APD and HD. LDL-CHOL in APD and HD were higher than in controls (APD p<0.0001; HD p<0.05), but failed to differentiate between two dialysis modalities. TGL levels behaved in the same way. Conclusions: The elevated sE-selectin concentrations in all patients show the role of endothelium in atherogenesis in CKD children. Thus, the sE-selectin augmentation may serve as an early marker of endothelial activation, appearing prior to inflammation (unchanged hsCRP, IL-4). Increased sEselectin and cholesterol levels in APD patients prove that children on peritoneal dialysis are more prone to atherosclerosis than those on hemodialysis. Background: End-stage renal disease (ESRD) is associated with an increased risk of cardiovascular morbidity and mortality. According to recent data, arterial stiffness measured by aortic pulse wave velocity (PWV) and augmentation index (AIx) is a strong independent predictor of cardiovascular mortality in adult ESRD patients. Few studies have been reported regarding arterial stiffness in the paediatric renal population. Methods: Aortic PWV and AIx (difference between the first and the second systolic peaks on the aortic pressure waveform divided by the pulse pressure) were determined in 14 haemodialysis children (10 boys; age 12±4 years) by applanation tonometry using a Sphygmocor device. Seven of the HD patients (5 boys; age 12±3.5 years) received a renal transplant (Tx) and were restudied (6±2 months post Tx). The immunosuppressive regimen included basiliximab induction, cyclosporine, mycophenolate mofetil, and steroids. Results: In the HD population, aortic PWV (6.3±1.3 m/s) was correlated with age (p=0.019), weight (p=0.036), height (p=0.0036) and systolic blood pressure (p=0.0038). In the transplanted cohort AIx decreased in six children out of seven after transplantation (7.57±9.45% on HD versus -6.57±19.7% after Tx). No significant change was observed for aortic PWV (6.37±1.18 m/s on HD versus 6.86±1.87 m/s after Tx).

Objective: To study the pathogenic role of host and Escherichia coli virulence factors in the development of E. coli febrile urinary tract infection (UTI) in children with acute cystitis (AC), acute pyelonephritis (APN) and renal scar. Materials and methods: Isolates recovered from 125 children consecutively admitted to the hospital with E. coli febrile UTI that diagnosed as AC (n=36) or APN (n=89) were retrospectively enrolled into this study. Virulence genes of E. coli, that included papG genes (classes I-III), aer, cnf1, fimH, hlyA, afa, sfa/foc, iha, usp, iroNe and ompT, were detected by polymerase chain reaction analysis. Results: Young age (=<5 months), male sex were more frequently associated host factors for patients with APN, but old age (>5 months) and female sex were more frequently associated with renal scar formation. After multilogistic regression analysis, with regard to E. coli virulence factors, the papG class II gene might play a more important role in the development of E. coli APN. However, iha was significantly higher in young children with acute pyelonephritis. Afterwards, age, gender, duration of fever before admission, and CRP level were considered as potential confounders for the further multivariate analyses, specifically estimating the relative risks of E. coli genotypes to the incidence of acute pyelonephritis and renal scar by age group and the existence of Vesicoureteral reflux. Odds ratios with 95% confidence intervals for each variable were utilized to estimate the relative risk of acute pyelonephritis and renal scar. In addition, there were no differences between young children and old children, if we excluded the factor of vesicoureteral reflux (VUR). Conclusion: Both host and E. coli virulence factors contribute to the development of febrile UTI, APN and renal scar.

Since 2/06 we have started an acute peritoneal dialysis (duration 1-61 days) in 8 infants (age 7 days to 9 months) with the use of the Baxter Acute Set for Children under constant warming of the complete dialysate inflow tract to 37 °C (Barkey System). As dialysate solutions we chose a Glucose/Bicarbonate/Lactate solution (Physioneal 40) in all patients and in 4 patients a mixture of this solution with a 1.1% amino acid solution (Nutrineal) in a 3:1 ratio. The body weight before the renal insufficiency was 1.3 to 5.2 kg. In 5 patients the renal failure followed cardiothoracic surgery. The handling of the system was easy. Because of obstruction by omentum and fibinous layers, respectively, the dialysis catheter had to be cleared surgically in 2 patients. Body temperature could be kept constant and in the normal range, even with low body weight and intensive dialysis (as measured by dialysate volume per kg body weight and day). In the infants dialyzed with the Glucose/Amino Acid-Mixture a decreased loss of albumin through the dialysate (as measured by the necessary intravenous albumin substitution), a better glucose homeostasis (less episodes of hyperglycemia and less need for insulin infusions) as well as a better acid-base control (less episodes of metabolic alkalosis) could be found. The detected tendency to a better homeostasis (concerning body temperature, serum albumin, blood glucose and acid-base) with this dialysis system and the used dialysate solutions could help to increase the survival chances of infants with renal failure. This will be evaluated prospectively. Objectives: Varicella-zoster-virus (VZV) infection can cause significant morbidity and mortality in the immunocompromised patient. Since there is no clear correlation between antibody titers and protection monitoring after VZV vaccination is unclear. Patients and Methods: Serum samples of nineteen pediatric transplant recipients were investigated for VZV IgG antibody titers and avidity (ELISA test). A relative avidity index (RAI) <40% showed evidence for low-avidity antibodies, an RAI >60% high-avidity antibodies, borderline avidity inbetween. The control group consisted of 27 healthy children. 22 had suffered from varicella infection after wild-virus contact, 5 had undergone Varicella vaccination. As there was no difference between diseased and vaccinated controls both subsets were treated as one group. Results: Median VZV IgG antibody titers were 560 U/ml (range 100-2600) for transplanted children and 790 U/ml (range 50-2300) for control subjects (n. s.). Median RAI was 83% for transplant patients and 90% for controls (p=0,04). There was no correlation between RAI and antibody titers in either group. RAI increased significantly with time after vaccination or infection in both groups. Despite protective antibody titers after vaccination and an RAI of 68% one transplant recipient showed a moderate VZV infection that required antiviral treatment. Postinfectious course showed an increase of RAI up to nearly 100%. Conclusion: VZV IgG antibody avidity might be a pathbreaking parameter regarding decision making for a second vaccination before transplantation or preemptive treatment in a transplanted patient in case of exposure.

In Japan, almost half of children with ESRD received renal transplantation and more than 90% of those were living kidney transplants from their parents. Burden of ESRD during childhood frequently causes psychosocial problems in their families, including parental relationship problems. We investigated how parental divorce or death affected the choice of renal transplantation in children. Patients and Methods: in 68 children younger than 20 years old who started renal replacement therapy in our hospital, percentages of the children losing a parent or parents by divorce or death were investigated. We compared renal transplantation rates and percentages of fathers as kidney donors between those living with both parents and those without. Results: in observation periods (4.2±3.3 years), 43 (63%) received renal transplants from 40 living and 3 deceased donors. Nineteen children (28%) lost a parent or parents by divorce (n=16) or death (n=3). In all divorced families, mothers got parental authority. Ten parents divorced during CKD period, 2 after start of dialysis, and 4 after transplant. Of 49 children living with both parents, 31 (63%) transplanted with kidneys from 9 fathers, 20 mothers, and 2 deceased donors. Of 16 children whose parents divorced, 11 (69%) transplanted from 4 fathers (2 just before and 2 after their divorce), 5 mothers and 2 other family members. However, in 3 children at least one parent died, only 1 (33%) transplanted from a deceased donor. Conclusion: a high parental divorce rate from CKD period was observed in children with ESRD, suggesting burden of the disease on their families. Renal transplantation was preferred even in divorced families and divorced fathers still were willing to donate kidneys to their children. Objective of study: To determine the importance of gastrointestinal evaluation in pre-transplantation phase in pediatrics with End Stage Renal Disease (ESRD). Methods: Twenty four children with ESRD (13 female, 11 male) mean age 14.7 (±3.4) years on maintenance hemodialysis were included in this study. Upper gastrointestinal endoscopies were performed and four gastric antral and duodenal biopsy specimens were obtained for urease test and histological study for all patients. Serum gastrin levels were measured in all patients, too. A control group was chosen to compare the rate of H. pylori infection using student's t. test. Results: Gastrointestinal symptoms were present in 16 (67%) of 24 patients. Seventeen (71%) patients had abnormal upper gastrointestinal endoscopic findings. H. pylori was detected in 66% of patients and 20% in control group (p<0.001). In symptomatic patients 75% had abnormal endoscopic findings and 63% had positive urease test for H. pylori infection. While, in asymptomatic cases these rates were 30% and 75%, respectively. Seventy one percent of patients with gastrointestinal lesions and 50% of patients with normal endoscopic examination were infected. High serum gastrin levels in infected and non-infected patients were detected in 75% and 12.5%, respectively (p<0.001). Conclusion: We demonstrated a significant number of patients with peptic ulcer diseases and H. pylori infection and secondary hypergastrinemia. This study showed that, clinical symptoms are not a reliable predictor of gastrointestinal problems. Our results emphasize the importance of periodic, and also pre-transplant gastrointestinal evaluation in these patients to find out their problem and manage appropriately. Key words: Renal failure, Hemodialysis, Peptic ulcer disease, Helicobacter pylori, Hypergastrinemia.

Background: Preservation of a stable allograft function in children following renal transplantation (RTx) depends on various factors including genetic variability. The gene of the angiotensin I converting enzyme (ACE) has been shown to influence allograft function. We therefore analysed various polymorphisms of the renin-angiotensin system in 91 children following RTx and 32 kidney donors and associated genotypes with loss of renal function. Patients and methods: 91 children and adolescents (60 male, 31 female, mean age at transplantation 9.7±5.2 years) with stable renal function and observation period exceeding 6 months were included. Mean follow-up time was 5.4 years (0.5 to 16 years). DNA was extracted from all recipients and 32 donors and genotyped using RFLP. The following polymorphisms were studied: Renin 18 G/A; ACE I/D; angiotensinogen (AGT) 235 Met/Thr and angiotensin II receptor type-1 (AT1R) 1166 A/C. The slope of glomerular filtration rate (GFR) was determined by linear regression analysis and correlated with the genotype. Results: Allelic frequencies were not different from healthy controls. Genotypes of renin, AGT and AT1R showed no significant association with the slope of GFR but patients homozygous for the ACE-D-allele had a significantly steeper decline of GFR when compared to homozygous carriers of the ACE-I-allele (slope DD: -4.3±0.8 vs. II: -1.3±1.1; p=0.035). The DD-genotype was also present in 11 out of 32 donors and in four cases a DD-recipient received a kidney from a DD-donor. Those four patients showed a more pronounced decline of GFR (-5.2±0.5; p=0.002 ). In addition, DD-recipients had a significantly increased systolic and diastolic blood pressure before RTx. Conclusions: The DD-genotype is associated with a faster, non-immunological loss of graft function which has to be evaluated in prospective studies.

Year Large Single-center Review B. Warshaw, L. Hymes, L. Greenbaum, S. Amaral

From1995-2006, 207 children received renal transplants at Emory University/Children's Healthcare of Atlanta of whom 29 (14%) had nephroticsyndrome (NS) as their primary diagnosis (27 FSGS, 2 minimal change). All children received calcineurin-based immunosuppression. Thirteen children (45%) developed recurrent NS within the first week post-transplant and received plasmapheresis (PP) 3-5 times weekly. Nine (70%) had complete resolution of proteinuria. Two who responded to PP suffered graft loss fromlate recurrences of NS at 7 years. NS did not resolve with PP in 4 children who suffered either delayed function (1) or early cessationof function (3); each of the latter lost their grafts within the first 3 months. 16 patients did not have recurrences of NS. Comparison of these 2 groups showed significantly increased riskfor recurrence with younger patient age (p<0.006), interval <3 years from onset of NS to ESRD (p<0.02), and living donor source (7/9=78% LD vs 6/20=30% DD; p<0.02). No differences were seenfor HLA match, donor age, gender, or African American race. Actuarial graft survival for children with recurrence was 70% at1 year and 60% at 2 years vs. 100% & 92% for patients without recurrence. Conclusions: NS recurred in 45% of children with NS as their primary cause of ESRD. Risk factors for recurrence included younger age, interval <3 years from onset of NS to ESRD, and living donors. Most recurrences responded to PP (70%); failure to respond was associated with delayed or early cessation ofrenal function & early graft loss. The incidence of recurrence was strikingly high (78%) among living donor recipients, suggesting a need to explore prophylactic strategies such as preemptive PP in this group. Methods: A single-centre retrospective case-controlled study including 24 children <3 yr (G1) and 24 matched kidney Tx recipients older than 3 yr ofage (G2). Patients were matched for donor type and Tx period. Kaplan-Meier method was used for patient and graft survival. Results: 23 Tx were performed using deceased donors in both groups. Median recipient age, weight and height at Tx in G1 were 1.5 [0.6-2.7] yr, 9.1 [5.6-11.1] kg and 74.8 [64.5-87.0] cm, respectively, while median age in G2 was 11.2 [3.3-17.2] yr. Hypoplasia-dysplasia wasmore frequent in G1 (42 vs 21%). Median HLA-DR mismatch, time ondialysis and number of blood transfusion before Tx were not different. In G1, kidneys were placed intraperitoneally and most of vascular anastomoses were done on distal aorta (83%) and inferior vena cava (88%). Median follow-up was 8.7 [0.02-15.9] yr and 6.5 [0.3-15 .6] yr inG1 and G2, respectively. Patient survival was 94% at 5 yr and 88% at 10yr in G1; 3 patients died in G1 (2 PTLD, 1 recurrence of primary disease), none in G2. Fiveyear graft survival was 79% in G1 and 77% in G2. Acuterejection episodes occurred in 46% in G1 and in 67% in G2 (P 0.15 ). Chronic rejection led to 3 late graft losses in G2 (5.2 to 6.9 yrafter Tx) vs 0 in G1. Renal function did not differ between the 2 groups during the first 5 yr post Tx. The average height gain was better in G1 at 5 yr post Tx (+1.3 SDS vs. -0.1). Primary disease recurrence was observed in 4 cases (1 in G1) causing graft lossin 3 cases. Two arterial thromboses were observed in G1 causing 1 earlygraft-loss. Conclusion: The outcome after cadaveric kidney transplantation is as good in children under 3 yr of age at transplantation as in older recipients in our experience.

C. Garcia, V. Bittencourt, D. Malheiros, A. Tumelero, J. Antonello, A. Oliveira, V. Garcia

Cancer is an increasingly recognized problem associated with immunosuppression. Recent reports, however, suggest that sirolimus (SRL) has anti-cancer properties that could address this problem. Aim: To report a retrospective analysis of preliminary results of 6 patients who received SRL because of post-transplant de novo malignancies in a consecutive cohort of 348 pediatric kidney recipients. Patient and methods: We retrospectively evaluated the efficacy and safety of SRL in 6 pediatric renal transplantation recipients, who were 12±7 years when converted to SRL. The 6 post-transplant de novo malignancies were: gall bladder and hepatic leiomyoma (n=1), Wilms tumor in the native kidney (n=2), PTLD (n=2) and HPV-associated neoplasia. The immunossupressive regimen at the malignancy diagnosis was tacrolimus/cyclosporin, MMF/azathioprin and prednisone. All were converted to double immunossupression with sirolimus at a standard dose of 2mg/day (TL5-10ng/ml) and prednisone. Patients with PTLD were also treated with rituximab, and the patients with Wilms tumor received chemotherapy. Mean follow-up after SRL conversion is 35±25 months. Results: All patients were maintained with SRL and PRED without rejection, with good renal function and no cancer recurrence (follow-up 6 to 75 months). The patients with Wilms tumor are still on chemotherapy. Follow-up control after SRL conversion in the 6 patients: Conclusion: Although the intraperitoneal group had characteristics associated with increased surgical risk (they tended to be younger and smaller, with a higher incidence of aortic anastomoses and a higher incidence of multiple vessels), surgical complications were significantly lower than expected in the extraperitoneal group 7% v. 33%. Objective of study: Proteinuria is a frequent complication in adult patients after renal transplantation (R-Tx) and is associated with poor graft survival. In children, there are no studies focusing primarily on proteinuria after R-Tx. The aim of this study was to investigate the prevalence of proteinuria in children after R-Tx and to evaluate changes of proteinuria during a 2-yr study on intensified antihypertensive therapy. Methods: Protein excretion was measured in 24-hr urine and proteinuria defined as >96 mg/m 2 /day. Proteinuria was investigated at baseline, 1 and 2 years after intensifying of the antihypertensive therapy in children with uncontrolled hypertension at baseline (i. e. additional antihypertensive drugs given to children with blood pressure >95. pc). 33 children (13.7±4.3 yrs) out of 45 from our center fulfilled inclusion criterias (>6 months after R-Tx, no acute rejection (AR) in the last 3 months, no recurrent FSGS).

Results: The prevalence of proteinuria was 82% at baseline, 76% after 1 year (NS) and it decreased to 52% after 2 years (p<0.05). The mean protein excretion was 256±303 mg/m 2 /day at baseline, 224±208 after 1 year (NS) and it decreased to 134±88 after 2 years (p<0.01). Mean number of antihypertensive drugs increased from 2.1±0.9 drugs/patient to 2.7±0.8 after 2 years (p<0.01). Mean nighttime BP decreased significantly after 2 years. The number of patients on ACE-inhibitors increased from 19% at baseline to 39% after 2 years (p<0.05).

Conclusions: This is the first study on proteinuria in children after R-Tx. It showed that proteinuria is a frequent finding in transplanted children and that intensified long-term antihypertensive treatment using ACE-inhibitors can decrease not only BP but also proteinuria in these patients. Allograftrejection involves T cell activation and proliferation and multipleinflammatory components. Monocyte chemotactic peptide-1 (MCP-1) is achemoattractant and activating factor for monocytes. Interleukin-6 (IL-6) may contribute to monocyte recruitment, results intubulointerstitial damage. Cytotoxic lymphocytes induce target cell death by ligation of the Fas-FasLigand. Allelic polymorphisms in recipient genes coding for them reported to beassociated with variations of outcome in renal transplantation. The aim was to investigate impact of MCP-1 -2518 A/G and IL6-174 G/C, FAS-670 A/G polymorphisms on acute allograft rejection (AR). There were 20 males and 27 females, 19±4.6 years meanly; 21 of the graftscame from living-related donors, 26 were from cadavers. The controlgroup consisted of 150 unrelated, healthy individuals with similar ageand sex. AR group was composed by 17 patients experienced at least one AR episode within the first 6 months of transplantation. The non AR group was comprised by 30 kidney transplant patients without AR. There was no significant difference between renal transplant patients and healthy controls in genotype distribution of allelic frequencies of IL-6, FAS and MCP-1 polymorphisms. While IL-6 and FAS gene polymorphisms had no effect on the incidence of AR episodes, there was significant association with MCP-1. The distribution of the genotypes for MCP-1 -2518 A/G in AR group were AA/AG/GG 23, 6%, 64, 7%, 11, 7% respectively. The distribution of the genotypes for MCP-1 -2518 A/G was AA/AG/GG 60%, 30%, 10% in nonAR group respectively. The carriage of G allele at -2518 position of MCP-1 gene has a significant association with AR (OR: 4, 87, 95%, CI: 1, 27-18, 5). The IL-6 and FAS gene polymorphisms had no effect on the incidence of AR. MCP-1 -2518 G allele carriage increases the AR risk in Turkish renal transplant patients. The high recurrence rate of Focal Segmental Glomerulosclerosis (FSGS) in transplanted kidney recipients suggests the hypothesis that such patients have a circulating factor that changes glomerular capillary permeability. Serum from patients with FSGS increases glomerular permeability to albumin, and this permeability factor was partially identified as a protein. The removal of this protein by plasmapheresis (PP) decreases proteinuria.

Object: The aim of this paper is to provide data about the therapeutic effect of PP in FSGS children with recurrence in the transplanted kidney. Methods and results: Twenty eight pediatric kidney transplant recipients had FSGS as cause of renal failure from 1990 to 2007 in our center, confirmed by biopsy pre-transplant. Seventeen of these (60.7%) had a recurrence (proteinuria >1 g/m 2 per day associated with hypoalbuminemia). The mean age was 12±4.3 years, 85, 7% were Caucasians and 67, 8% were performed with living donor. Since 2001, patients who presented FSGS recurrence were treated with 10 cycles of PP (3 cycles/weekly), initiated immediately post-recurrence (n=11). Immunosuppression comprised of cyclosporin in high doses (C 2 levels of 1700-1800 ng/ml) or tacrolimus (TL=10 mg/dl), mycophenolate sodium or mofetil (until 1997 azathioprine was used) and prednisone. Among patients who received PP (n=11), 7 (63.6%) achieved a complete remission. There were no cases of remission among those six patients who were not treated with PP. Those who achieved remission after PP had no recurrence. The patients treated with PP had infectious complications: one patient had cytomegalovirus disease and two patients had varicella.

Conclusion: PP appears to be effective in treating recurrent FSGS following kidney transplantation. It should be started as soon as possible. Because the calcineurin inhibitors (CNI) cyclosporin A (CsA) and tacrolimus (Tac) are drugs with a narrow therapeutic index, individualization of CNI dosage by therapeutic drug monitoring is indisputable. However, the optimal strategy for monitoring CNI therapy is currently under debate. Dosing of CNIs according to the molecular effect of the drug on its target cells could optimize immunosuppressive therapy with CNIs. For this purpose, we developed a reliable, precise, and robust whole blood assay based on the measurement of the expression of three NFAT-regulated genes (IL-2, IFNg and GM-CSF) in PMA/ionomycin-stimulated lymphocytes before and 1.5 (Tac, C 1.5 ) or 2 hrs (CsA, C 2 ) after oral drug intake. The inhibition of genes in this assay is independent from other commonly used immunosuppressive drugs and reflects calcineurin inhibition expressed as residual NFAT activity. In a pilot study, 40 patients (mean age 14 yrs, mean time period posttransplant 42 mo.) were analyzed. In CsA-treated patients (n=12), a mean C 2 concentration of 380 ng/ml (range, 180-900 ng/ml) corresponded to a mean residual NFAT-activity of 32% (range, 3-115%) ; the correlation between individual residual NFAT-activity and C 2 was moderate (r=0, 59, P<0.05). At a CsA-C 2 of 400 ng/ml, the residual NFAT-activity varied between 8% and 25%. In Tactreated patients (n=28), a mean C 1.5 concentration of 18 ng/ml (range, 6-54 ng/ml) corresponded to a mean residual NFAT-activity of 40% (range, 7-70%); the correlation between individual residual NFAT-activity and C 1.5 was also only moderate (r=0, 60, P<0.05). Conclusion: These data indicate that there is a considerable inter-patient variability of residual NFAT-activity at a given maximal CNI blood concentration. Ongoing studies are validating this assay regarding clinical outcome criteria of immunosuppression such as acute rejection and infections. HUS due to antibodies against factor H (HUSaFHAb) is a very rare disease for which a limited experience in its management is available. We present a case of HUSaFHAb who was transplanted but lost her graft after only 4 mos. In Aug 2002 a 5-mos old child was admitted for a D-HUS which did not go into remission and required chronic peritoneal dialysis. No FH and MCP gene mutation were detected nor ADAMST-13 activity was decreased. aFHAb were not searched at that time. In Apr. 06 the child underwent cadaver renal transplant (rTx). The immunosuppressive regimen was basiliximab-prednisone-cyclosporine-mycophenolate mofetil. Fifteen days after rTx, following surgery for urinoma, the child exhibited an HUS relapse with thrombocytopenia, haemolytic anemia and increased serum creatinine (sCr). High aFHAb were detected (2400 AU/mL). Four plasma exchanges (PE) were performed over 2 wks with a drop of aFHAb to control level (196 AU/mL) and a remission of HUS. Until the end of Aug, aFHAb remained low (<400 AU/mL) and the child was well (sCr range: 0.6-1.2 mg/dL). In early Aug, the patient was shifted to Tacrolimus for severe hypertrichosis with a fluctuation of its plasma level (lower recorded value: 1.4 ng/mL) Signs of acute rejection developed and 4 metilprednisolone (MTP) pulses brought sCr to baseline level. In Oct. 06, following an URTI, the child presented with severe proteinuria (uPr/uCr: 15, 6) without other clear signs of HUS recurrence. Since aFHAb were increased (849 AU/mL), PE was restarted but an acute hemorrhagic complication (hemotorax) occurred and PE had to be interrupted. Septicemia followed and the child became anuric. The renal biopsy performed 3 days later showed signs of glomerular and vascular thrombotic microangiopathy. Renal function did not recover despite MTP pulses and 4 PE. In Nov the child was back to PD and in Dec the graft was removed. Background & aims: Recently, the role of nitric oxide (NO) in the pathogenesis of idiopathic nephrotic syndrome (INS) has been intensively investigated. However, its rapid turnover has made us impossible to investigate the quantity and the source. As we have developed a novel method for quantitative analysis for NO by a new fluorescent indicator, 4, 5-diaminofluorescein (DAF-2), its amount produced by both T and B lymphocytes in INS was studied.

Methods: Five children with steroid-sensitive INS (mean age: 4.0 y) were included in this study, together with 7 children with other renal diseases (mean age: 5.0 y) such as chronic glumerulonephritis and Alport syndrome with significant amount of proteinuria, and 10 healthy adults (mean age: 28.0 y) for the control. NO production from CD3+ cell and CD19+ cell was investigated by a flow cytometry using DAF-2. Results were expressed as mean fluorescence intensity and were compared among the groups.

Results: The amount of NO produced by CD3+ cell and CD19+ cell in children with INS was significantly greater than those in children with other renal diseases and healthy adults (CD3+ cell: 57.5±6.8 [mean±SD], 27.6±7.0, and 21.7±2.1, respectively; CD19+ cell: 35.7±3.5, 24.9±3.9, and 18.9±2.3, respectively, p<0.05). Additionally, both CD3+ cell and CD19+ cell during nephrotic relapse produced more NO than in nephrotic remission (p<0.05). Discussion: Patients with relapsing INS showed increased production of NO by both T and B lymphocyte. These findings indicate that NO plays some role in the pathogenesis of INS and suggest that an abnormal immune system may exist not only in T but also in B lymphocytes.

A. Bagga, A. Sinha, S. Menon, P. Hari

Aim: the treatment of patients with SRNS is challenging. Based on suggestions that B-lymphocytes are crucial in the pathogenesis of nephrotic syndrome, we examined the efficacy of rituximab (RTX) in patients with SRNS refractory to standard therapies. Methods: six patients (4 with initial, 2 late resistance), 3-16 yr old, were included; biopsy showed minimal change & focal segmental glomerulosclerosis in 3 each. All had previously received IV high-dose steroids, alkylating agents & calcineurin inhibitors (CNI) for 2-14 yr with periods of partial (PR; urine 1-2+) or complete remission (CR; urine trace/negative). All now had SRNS refractory to 6-months treatment with CNI. RTX (375 mg/sq. m) was infused IV every week for 4 weeks. Therapy with CNI and/or alternate-day prednisolone, & cotrimoxazole prophylaxis was continued. Patients were monitored for proteinuria and renal functions.

Results: at a median interval of 4 wk following the last RTX dose, CR was seen in 4 & PR in 2 patients. Remission was sustained in 4 patients, despite tapering doses of steroids & CNI. One case had relapse of nephrotic syndrome 6-months later, which responded to steroid treatment. At median follow-up of 28 wk, CR, PR and recurrence of nephrotic proteinuria (3-4+) were seen in 3, 2 and 1 patients respectively. Mean urine albumin-to-creatinine ratio was 8.9 at baseline and 0.9 at followup; respective blood levels of albumin were 1.4 and 3.7 g/dl & cholesterol 481 and 221 mg/dl (all P<0.01, ANOVA); difference in leukocyte counts and levels of IgG were not significant and none had serious infections.

Conclusions: this is the first report on the efficiacy of RTX in sustaining remission in patients with SRNS. Therapy with this agent appears promising for difficult SRNS, with a better risk/benefit profile than other medications. Quantitative or functional deficiency of Factor H results in uncontrolled complement activation and is an important cause of familial hemolytic uremic syndrome (aHUS). Factor H-related proteins (FHR) constitute a protein family which share structural and most likely functional similarities to Factor H. We here describe complete deficiency of FHR-1/-3 as novel cause of aHUS. Factor H and FHR-1/-3 were quantified by ELISA and were further analyzed by Western blot using specific antibodies. Complement activation was determined by measuring C3 and C4. Serial Hgb (g/dl), platelet, creatinine (mg/dl), and LDH (U/l) were measured.

A 12 year old girl presented with a 5 day history of lethargy, pallor, vomiting and hypertension. Hgb was 6 g/dl, platelets 40x10 9 /l and creatinine was 6.8 mg/dl. Initial therapy consisted of packed red cell and platelet transfusion, followed by steroid therapy. Representation occurred 7 weeks later with hypertension, edema, persistent anemia thrombocytopenia and renal dysfunction (creatinine 4.5 mg/dl). Renal biopsy demonstrated features of chronic thrombotic microangiopathy. Low C3 levels indicated activation of the complement system. While Western blot analysis showed normal Factor H level, FHR-1/-3 was absent. By repetitive plasma infusion and plasmapheresis, the cycle of hemolysis and thrombocytopenia could be disrupted. Chronic periodical plasma infusion q 14 days resulted in regression of renal impairment to a degree (current baseline creatinine 1.5 mg/dl).

In conclusion, FHR-1/-3 are thought to have co-factor activity and play a role in complement activation in aHUS. Deficiency of FHR-1/-3 may lead to a subclinical form of aHUS such that patients may initially present with features of chronic renal failure. However, factor replacement therapy may lead to regression of renal impairment.

S. Choudhry Objectives of the study: The aim of the study is to investigate the long term prognosis ofsevere childhood IgA nephropathy after 2 years combined therapy. Patients: We examined 39 patients who had entered theJapanese pediatric IgA nephropathy treatment study group between 1990and 1994, had been treated with 2 years combined therapy (combinationof prednisolone, azathioprine, dipyridamole and heparin/warfarin) andhad been followed for more than 3 years after the therapy. Significantproteinuria is defined as more than 0.2g/m 2 /day. Results: Mean age at onset was 11.4 years (4-16 years), proteinuria at diagnosis was 1.11±0.84 g/m 2 /day, proteinuria after the combined therapy was 0.17±0.22g/m 2 /day and mean follow-up period after the combined therapy was 7.2 years (3.2-9.9 years). Proteinuria improved in all patients during thecombined therapy (p<0.0001). The final prognoses were as follows: 21 patients (54%) showed no proteinuria, 15 (38%) showed proteinuria withnormal renal function and 3 (8%) proteinuria with decreased renalfunction. We compared the clinical and pathological parameters betweenpatients with proteinuria (n=18) and those without proteinuria (n=21) at the last observation. Period between disease onset and start of treatment, glomeruli showing crescents before the combined therapy (%) and glomeruli showing pathological changes after the combined therapy (%) were the significant risk factors for the proteinuria at the last observation. Logistic multivariable analysis revealed that glomeruli showing pathological changes after the combined therapy (%) was theonly independent risk factor for the proteinuria at the last observation.

Conclusions: Pathological activity of nephritis at the end of the combined therapy might correlate well with the final proteinuria and the long term prognosis.

S. Arun, A. Bagga, S. Bhatnagar, P. Hari, S. Menon, S. Saini

Aim: Relapses in SSNS of ten follow minor infections and are associated with perturbed T-cell function. Based on data that Zn supplements modulate T-cell function and reduce risk of infections, we examined its efficacy in reducing relapses in patients with SSNS. Methods: In this double blind RCT, 81 consecutive patients with SSNS 1-16 yr old, stratified into frequent (FR=52) and infrequent (IFR=29) relapsers, were randomized to 12-months therapy with Zn (10 mg daily) or placebo. Patients with FR also received long-term, alternate day prednisone. Relapse and infection rates were monitored monthly. Blood levels of Zn, sIL2r, IL4 and interferon (IFN) were measured at baseline, relapse andend of study.

Results: Patientsin the Zn (n=40) and placebo (n=41) groups had similar baseline clinical & laboratory features. The former showed 20% lower frequency of relapses (difference in means -0.2; 95% CI -0.7, 0.3) with trend towards reduction from 6-months onward. A higher proportion (44.7%) of patients in the Zn group had sustained remission compared toplacebo (27.5%). Reduction in relapse rates was higher in FR receiving Zn vs. placebo (-0.3; CI -0.9, 0.3); respective sustained remission was seen in 46% and 16% patients (relative risk 0.5; CI 0.3, 0.9; P 0.02). No differences were found in infection rates, and levels of Zn, sIL2r & IL4; levels of IFN were higher in those receiving Zn compared to placebo (P=0.02).

Conclusions: Zn supplementation for 1-yr was effective in maintaining remission and reducing relapse rates. The effect was mediated not by reducing infections but perhaps through effect on Th1 cytokines. While Zn therapy appears promising, these results need confirmation in patients with frequent relapses and perhaps at a higher dose. Background: N-glycosylation process in the endoplasmic reticulum (ER) is tightly regulated and orchestrated by many factors such as chaperones and energy systems. We showed that adequate Nglycosylation is crucial for nephrin to assemble to the plasma membrane (JASN, 2002) .

Additionally we recently demonstrated that the ER stress evoked by glucose starvation induces hypoglycosylated nephrin retained in the ER, which is rescued by dexamethasone (DEX) (KI, 2006) and immunosuppresant: mizoribine (MZR) (submitting). In the present study, we tested whether other ER stress inducer, hypoxia, could also interfere the alteration of nephrin N-glycosylation system and whether DEX and immunosuppressants rescue its defective process. Methods: Nephrin-expressing cell line was cultured either in 21% O 2 or 1% O 2 for 24 hours in the presence or absence of DEX, MZR and cyclosporin A (CsA), followed by Western blot analysis with nephrin, cytochrome C. Intracellular ATP concentrations were measured by the highperformance liquid chromatography. Protein expression of cyclophilin D (CyP-D), a component of mitochondrial permeability transition pore (MPTP), was tested in the samples from human glomeruli and cultured podocyte. Results: Hypoxia induced hypoglycosylated nephrin. CsA, but not DEX and MZR, inhibited the formation of this hypoglycosylated nephrin and rescued mature form. CsA inhibited the increase of cytochrome C in the cytoplasm caused by hypoxia. In addition, CsA partially rescued the decrease of intracellular ATP. CyP-D was distinctly observed in human glomeruli and located in podocytes. Conclusion: CsA inhibit the formation of hypoxia-induced hypoglycosylated nephrin through protecting the MPTP opening via selectively binding to CyP-D in the mitochondria, resulting in a recovery of ATP. CsA may exert direct action on the alteration of nephrin biogenesis induced by the ER stress. Background and objectives: In two previous randomized controlled trials (RCTs) we showed that treatment of severe childhood IgA nephropathy (IgA-N) with diffuse mesangial proliferation using prednisolone, azathioprine, heparin-warfarin, and dipyridamole reduced immunologic renal injury and prevented any increase of sclerosed glomeruli. In one of the two RCTs we also showed that treatment with prednisolone alone did not prevent a further increase of sclerosed glomeruli. Accordingly, the immunosuppressant is considered to play an important role in the combination therapy. Often however, we were unable to complete the azathioprine regimen due to its severe side effects. Therefore we considered that a different, but effective immunosuppressant would be worth trying. Mizoribine, like azathioprine, is an antimetabolite that exerts its immunosuppressant effect by inhibiting lymphocyte proliferation. Design, setting, participants, and measurements: In this pilot study, we administered mizoribine instead of azathioprine as part of the combination therapy for treatment of 23 children with severe IgA-N and evaluated the efficacy and safety of the regimen. Results: Eighteen patients reached the primary endpoint (urinary protein/creatinine ratio <0.2) during the two-year treatment period. The cumulative disappearance rate of proteinuria determined by the Kaplan-Meier method was 80.4%. Mean urinary protein excretion was reduced from 1.86 g/m 2 /day to 0.20 g/m 2 /day (p<0.0001). After treatment, the mean percentage of glomeruli showing sclerosis was unchanged in comparison with that before treatment. No patients required a change of treatment due to side effects.

The efficacy and safety of the mizoribine combination seems to be acceptable for treatment of children with severe IgA-N. Objectives of study: Alport syndrome is a hereditary renal disease which is normally diagnosed by either histopathological studies or a genetical analysis. We attempted to diagnose Alport syndrome by means of immunofluorescence staining of cultured cells with collagen type 4 alpha chains obtained from voided human urine specimens. Methods: The cells were cultured from the voided human urine of 1 patient with X-linked Alport syndrome, 1 patient with sporadic Alport syndrome, and 1 patient with autosomal-dominant Alport syndrome. For comparison purposes, controls cells were cultured from the voided human urine of 1 patient with IgA nephropathy, 1 patient with FSGS, and 1 patient with purpura nephritis. The cultured cells were stained by immunofluorescence techniques with collagen type 4 alpha 1, 2, 3, 4, and 5 chains. Results: In the cultured cells of the controls staining for collagen type 4 alpha 1 and 2 chains were observed both in the extracellular matrix and in the cytoplasm while for the staining of collagen type 4 alpha 3, 4, and 5 chains were observed in the cytoplasm. In cultured cells of Xlinked and sporadic Alport syndrome staining of collagen type 4 alpha 5 chain was lost or attenuated. In the cultured cells of autosomal-dominant Alport syndrome the staining patterns of collagen type 4 alpha 3, 4, and 5 chains were observed.

The staining patterns of the collagen type 4 alpha 5 chain in cultured cells of Alport syndrome correlated with that observed in renal biopsies obtained from Alport syndrome patients as reported previously. Hence, the staining of cultured cells with the collagen type 4 alpha 5 chain obtained from voided human urine may therefore be a potentially useful means of diagnosing Alport syndrome in a non-invasive manner. The aim of our study: was to examine zeta chain expression in CD4+, CD8+ T cells and NK cells from INS children in active phase of the disease and in remission and to assess the effect of 24 h and 72 h anti-CD3 + rIL-2 stimulation on zeta chain expression. We enrolled 11 INS children in relapse before initiating the therapy, 12 INS children in complete remission of proteinuria on prednisone for 2-4 weeks (2mg/kgBW/d) and 15 age-matched controls. Zeta expression was determined by flow cytometry as mean fluorescence intensity (MFI). Results: CD4+cells: MFI in relapse was higher than in remission and in controls. Anti-CD3 + rIL-2 stimulation had no impact on zeta expression in acute phase and in cotrols, but increased MFI values after 72h in pts with remission. CD8+cells: Zeta expression stayed unchanged irrespective of the examined group or antibody stimulation. NK cells: There were no differences between MFI values before stimulation and in relapse after stimulation. In remission and in controls antibody stimulation decreased zeta expression. In controls, MFI values for NK cells were higher than those for CD4+ and CD8+ populations, but this preponderance disappeared after 72h stimulation. In remission, that NK cell predominance vanished after 24 h stimulation. In relapse, MFI values in all cells were comparable and stimulation had no impact on lymphocyte proportions. Urinary protein, creatinine, and sCD80 were measured. sCD80 was measured using a ELISA kit. sCD80 was expressed as ng/g of urine creatinine. Data were analyzed using ANOVA and Spearman Rank Correlation (SRC) tests.

1) sCD80 urinary concentrations in patients with MLNS in relapse were higher than patients in remission, healthy controls and other patients with proteinuria (ANOVA p 0.0001) but similar to those seen in SLE.

2) In patients with MLNS relapse, sCD80 concentration did not correlate with urine protein/creatinine ratio (SRC, r: 0.1719, p: 0.297) 3) In 3 patients with MLNS, serial urine sCD80 concentrations were measured over a period a time. sCD80 was increased at the time of relapse and decreased toward normal range weeks before patients went into remission. Conclusion: Urinary sCD80 is elevated in MLNS patients in relapse. This increased urinary concentration is not due to the proteinuria, since sCD80 was not elevated in other patients with glomerulopathies and proteinuria. Upregulation of podocyte sCD80 during relapse may play a role in the pathogenesis of proteinuria in MLNS.

Aim: Patients with MPGN Type II/dense deposit disease (DDD) and atypical haemolytic uremic syndrome (aHUS) secondary to defective complement control are found to have a high prevalence of Y402H polymorphism of Factor H gene (CFH), which is linked to age-related macular degeneration (AMD). However, no studies have looked into an ocular phenotype of children with complement based renal diseases, yet. Methods: In two Pediatric Nephrology Centres all Patients with MPGN II/DDD and aHUS were identified and screened prospectively for the presence of Y402H polymorphism and drusen maculopathy. All patients have been on immunomodulatory therapy at the time of screening. Results: Four children were identified (male:female=3:1) with MPGN II/DDD and aHUS. There were two children in either group. The median (range) age at examination was 8.6 years (3.5 to 13.3 years). Of the four patients, all were found to have the Y402H polymorphism. None of the patients had evidence of drusen at the time of examination. Two patients with MPGN II/DDD and one patient with aHUS had additional Factor H mutations, which were thought to be responsible for the renal disease. Conclusion: In our study of children with MPGN II/DDD and aHUS we found a 100% prevalence of the Y402H polymorphism of Factor H gene, which puts these patients at higher risk for drusen maculopathy. Therefore, all children with either MPGN II/DDD or aHUS should be screened for Y402H polymorphism; and if found positive have regular follow-up ophthalmologic examination.

In the future, should Y402H be proven to be of functional significance with respect to complement control, there would be a role for plasma infusion or replacement of purified Factor H for the treatment of both the renal and the ocular phenotype. We previously demonstrated that Angiotensin-(1-7) is an endogenous ligand for the G-protein coupled receptor Mas. The aim of this study was to evaluate the role of Angiotensin-(1-7) Mas receptor in kidney structure and function by using transgenic mice with genetic deletion of the receptor Mas. Mas -/-(knockout) mice were compared to Mas +/+ (wild type) mice regarding renal function parameters and kidney histology. The animals were housed in metabolic cages to obtain 24-hour urine samples for measuring urinary volume, osmolality and microalbuminuria. At the end of the experiment, Mas -/-and Mas +/+ mice were sacrificed by decapitation to harvest the kidneys for histological analysis and immunofluorescence of collagen types III and IV. The quantification of collagen expression was determined by confocal microscopy (Zeiss LSM510). Urinary volume was significantly reduced in Mas -/-mice as compared to Mas +/+ animals (1.32±0.49 vs. 1.80±0.83 mL/24 hs in Mas +/+ mice, p<0.05). This change was associated with an increase in urinary osmolality (3846±796 vs. 3219±840 mOsm/kg in Mas +/+ mice, p<0.05) and albumin excretion (0.23±0.16 vs. 0.04±0.02 mg/24 hs in Mas +/+ mice, p<0.05). The histological analysis showed a significant reduction in the glomerular diameter in Mas -/-mice as compared to Mas +/+ animals (51.84±0.73 vs. 58.25±0.79 μm in Mas +/+ mice, p<0.05), where as any significant change was observed in tubular diameter. The immunofluorescence of Mas -/-kidneys revealed a marked increase of the expression of collagen types III and IV in periglomerular region as well as in external and internal medulla. Collagen IV was also augmented in mesangial area of Mas -/-mice. These results suggest that the receptor Mas is critical for the regulation of renal structure and function. A circadian rhythm in calciuria is evident with a peak after 18:00 h, a lower excretion overnight and a nadir in the early morning. During the peak period both Ca/creat ratio (figure) and calcium output frequently surpass the reference values of 0.21mg/mg and 4 mg/kg/day respectively. Conclusion: A significant circadian variation in calciuria is evident in normal school age children, with peaks surpassing commonly used reference values for hypercalciuria. This peak excretion is independent from urine output, glomerular filtration and intake. The average 24 h excretion of 4 mg/kg is rarely surpassed despite this peaks. The management of children with secondary hyperparathyroidism is complicated and should start early in the course of renal insufficiency. In spite of an optimal management hyperparathyroidism is sometimes uncontrolled and calcimimetics like cinacalcet hydrochloride which directly stimulates calcium sensing receptors and potently suppress PTH secretion are an alternative to parathyroidectomy. They are very promising agents, but paediatric experience is lacking. A 11 years old girl with a Bardet Biedl syndrome without medical care came last year with end stage renal failure. Thanks to daily hemodialysis, serum phosphate level was kept within normal limits and phospho-calcic product remains below 4.4 as recommended. In spite of this treatment, serum PTH level increased to 1297 ng/L. This toxic hyperparathyroidism with optimal monitoring of serum calcium, phosphate, vitamin D levels led us to start calcimimetics. A 1,5 mg/kg cinacalcet dose was administrated and induced a decline of PTH level to 684 ng/L one month later. A 11 years old boy with recessive polycystosis and chronic renal failure was treated with calciumbased phosphate binders and sevelamer hydrochloride but with a poor compliance and a free diet which led him to hyperparathyroidism (PTH to 813 ng/L). In addition, a parathyroid gland hyperplasia with two adenoma was individualized. Start of calcimimetics treatment (less than 1mg/kg) led to a rapid decline in PTH level from 813 ng/L to 457 ng/L. The two adenoma decreased in size.

In case of hyperparathyroidism, with close monitoring of serum calcium, phosphate, alkaline phosphatase and vitamin D levels, calcimimetics are an excellent alternative to surgery, with safe use and low dose in these cases. Preliminary favourable experience has been reported in children but paediatric experience is lacking. Side effects result from chronic administration of steroids. The aims of this study are to analyze graft function and metabolic effects of low dose and withdrawal of steroid therapy. This is a single center pilot, one arm and prospective study. Methylprednisone (MP) was decreased to 0.07±0.03 mg/kg/day (low dose) after 4 months. We studied changes in graft function, height velocity, lipid profile, body composition and bone mass after 1 year of low dose MP and after a 2 nd year following MP withdrawal. Patients received daclizumab induction; tacrolimus and mycophenolate mofetil. The inclusion criteria was 1 st living related graft and PRA <10%; 16 patients were enrolled and total follow-up was 2.5 years. Age at transplantation was 3.1-21 years, 5 females, 9 prepubertal, 7 postpubertal patients. Patients and graft survival were 100%, acute rejection (AR) occurred after 14 months of MP withdrawal in 2/9 (22%) prepubertal patients (Banff 97, 1B). In prepubertal patients, at the moment of steroid withdrawal and 1 year later creatinine clearance was 99.7±15.2 and 82.9±3.9 ml/min/1.73 m 2 , p<0.001; height velocity 6.9±2.5 and 7.4±2.9 cm/year, p: NS, with a height increment of 0.31±0.1 SDS, p<0.05 during the last year of follow-up. Graft function did not change in postpubertal patients. In all patients at the moment of steroid withdrawal and 1 year later lipid profile was normal; fat body mass 10.0±6.7 and 9.2±5.5 kg, p: NS; lean body mass 29.3±11.4 and 31.7±12.8 kg, p<0.02; total skeleton BMD -1.0±0.6 and -0.7±0.8 SDS, p: NS and lumbar spine BMD -1.3±1.04 and -0.86±0.86 SDS, p<0.05. This study demonstrates that low dose and steroid withdrawal allow catch up growth, normal lipid profile with no fat accumulation. Steroid withdrawal prevents bone loss with increment of lean body mass, but with a concerning rate of AR and graft function deterioration in prepubertal patients. Children with x-linked hypophosphatemic rickets (XLH) usually present with progressive disproportionate stunting. We therefore conducted a 3 year randomized controlled trial on theeffect of rhGH therapy on body anthropometry (28 parameter) in 16prepubertal children with XLH (each 8 patients in rhGHandcontrol-group). Age at baseline was 7.3±2.0 yrs (mean±SD), height was -3.2±0.8 SD, calcitriol dosage was 23 ng/kg x day, and phosphate dosagewas 55 mg/kg x day (each p>0.05 rhGH-vs. control-group).

Results: Within the whole study population longitudinal bodydimensions were more affected than transversal body dimensions aswell as circumferences (extremities/trunk). Leg length (-3.7±0.9 SD; p<0.0001) was the most impaired longitudinal parameterexplaining 90% of the overall variability of total body height, whereassitting height (-1.7±0.8 SD) was the best preserved longitudinalparameter. Longitudinal body dimensions were significantly increased after 12 months rhGH-treatment (height +0.72±0.18 SD; sitting height +0.61±0.39 SD, leg length +0.57±0.55 SD; arm length +0.74±0.59 SD; each p<0.001). In contrast, progressive stunting was noted in control patients (height -0.16±0.42 SD; sitting height -0.01±0.24 SD; leg length -0.1±0.56 SD; arm length -0.01±0.26 SD; each p<0.001 vs. rhGH-group). RhGH treated patients showed a significant increase in all transversal body dimensions (each p<0.001), as well as a decrease in skin folds (range -0.2 up-to -0.9 SD; each p<0.001).

One year rhGH treatment in severely growth retardedprepubertal children with XLH leads to improvement of longitudinal bodydimensions, harmonization of body (i. e. transversal body dimensions & body proportions), and decrease of body fat. Thalassemia is an hemolytic anemia characterized by decreased production of β globin. The chronic hemolysis requires frequent bloodtransfusions that caused hemosiderosis, including iron deposition in the kidney. Removal of excess iron via iron chelators, the most commonof which is Desferal produce iron excretion in urine and stool. Few studies have been published, the studied patients, mostly adults, exhibited proteinuria, aminoaciduria, low urine osmolarity and excess secretion of the proximal tubular function markers, N-acetyl-D-glucoseaminidase (NAG) and β2 microglobulin. The iron accumulation may causes lipid oxidative peroxidation and this oxidative process cause's tissue damage.

In this study we examined 40 thalassemia major patients treated with Desferal. The degree of hemosiderosis was determined by measuring serumiron and ferritin. 12 children without iron metabolism disorders orrenal disease serve as controls. The renal and tubular function was analyzed.

No differences in Creatinine clearance, blood HCO3, Na and K Fe, Tmp/GFR was found. Serum uric acid was equal in the two groups but itsurine excretion was significantly higher in the thalassemic group probably due to persistent hemolysis. The NAG level and its ratio to Creatinine were significantly higher compared to the control group. The results of our work showed that most of the thalassemic patients have sub clinical disturbances in tubular function and high NAG in theurine.

These results raise the question of treating thalassemic patients with oral chelators which removes iron from cells preventing the oxidative process; moreover, and add antioxidants which may prevent the deposition of iron in tissues. In light of these findings, it would be advisable to routinely check glomerular and tubular function as part ofthe follow-up in these patients.

Objectives of study and methods: Little information is available on the long-term follow-up in patients with biallelic mutations in the two genes SLC12A1 and KCNJ1, encoding the bumetamidesensitive Na-K-2Cl cotransporter and the in wardly rectifying renal potassium channel, respectively. We evaluated the long-term follow-up (>7 years) in 12 patients with these two forms of Bartter syndrome. The SLC12A1 and KCNJ1 genes were screened by DHPLC and sequencing techniques.

Results: The long-term follow-up period was 7 to 22 years, median 11, after diagnosis, in 8patients with mutations in SLC12A1 (4 homozygotes, 4 compound heterozygotes) and 4 patients with mutations in KCNJ1 (2 homozygotes, 2 compound heterozygotes) genes. Medical treatment with indo methacin at last follow-up control including supplementation with potassium in 7patients and medical treatment with indomethacin in 10 patients (meandose 1.1 mg/kg/day). In two patients (one with SLC12A1 and another one with KCNJ1 mutations) growth hormone (GH) deficiency was detected with specific tests. Both patients were treated with recombinant human GH. At the end of follow-up, body height was <3° percentile for agein 2 of the 12 patients, 1 of whom with GH deficiency and body weightwas <3° percentile for age in 3 patients (none of them with GH decifiency Conclusions: these data demonstrate that some patients with biallelic mutations inthe SLC12A1 and KCNJ1 genes tend to present slight impaired glomerular kidney function after a median follow-up of 11 years and that growth retardation and GH deficiency are often present in these patients.

The Cytosolic C-Terminus of NHE3 does not Mediate its Apical Localization or Baseline Activity -Implications for Blood Pressure and PH Homeostasis The epithelial sodium proton exchanger, NHE3, is expressed in the apical membrane and subapical endosomes of the proximal tubule. Apical localization is fundamental to proximal tubular Na+, water and HCO3-absorption, a process necessary for the maintenance of plasma pH and blood pressure. Moreover the redistribution of NHE3 between these compartments alters its activity. For example, acute hypertension leads to an increased endomembrane accumulation of NHE3 and pressure natriuresis. NHE3 is composed of a N-terminus with 12 transmembrane helices and a cytosolic C-terminus. The former is necessary for sodium-proton exchange while the latter regulates activity. The goal of our studies was to evaluate the contribution of the cytosolic C-terminus to apical localization and therefore to NHE3 function. To this end we generated a series of NHE3 constructs with sequential deletions in the cytosolic C-terminus. All constructs contained an extracellular epitope tag to facilitate the delineation between cell surface and endomembrane NHE3. Stable renal epithelial cell lines were generated expressing each construct. Surprisingly, even when the entire C-terminus was deleted NHE3 was still detectable at the apical membrane. We proceeded to evaluate the activity of the truncated exchangers and found they retained activity. Finally, we assayed the attachment of NHE3 to the actin cytoskeleton (a process thought to be mediated by the C-terminus), by measuring their solubility in the weak detergent Triton X-100 and by measuring their mobility in the plane of the plasma membrane. Both assays confirmed that exchangers lacking the C-terminus retained their association with the plasma membrane. In conclusion, the cytosolic C-terminus of NHE3 is not necessary for apical localization nor baseline NHE activity. Further studies will be needed to confirm its role in specific regulatory processes. Background: IBU is used as a safer alternative to Indomethacine for PDA treatment. However, safety/efficacy balance has not been extensively studied. Animal and a few clinical studies suggested that IBU might also have significant side effects.

Objective: to evaluate renal function at one week of life in infants treated with IBU as compared to infants not exposed to IBU, within the first days of life.

Methods: multicentric prospective cohort study of 27 to 31 weeks gestation (GA) infants exposed or not exposed to IBU. Infants presenting with renal impairment at birth, urinary tract malformation, or contraindication to IBU treatment were excluded. Infants exposed to IBU were paired to Controls according to GA, centre and CRIB score. Creatinine clearance (mL/min/1.73 m 2 ) was measured for glomerular function evaluation; fractional excretion of sodium (FENa) and 1microglobinuria/creatininuria (1/UCr) for tubular function evaluation.

Results: 120 infants were studied: 60 exposed to IBU for PDA closure with 83.3% efficiency and 60 controls. Birth weight was 1100±278 g (Mean+SD), and GA 28.2±1.2 wks. Glomerular filtration rate (GFR) significantly decreased on day 7 in IBU exposed infants. Noteworthy, diuresis remained in the normal range, but was significantly lower after IBU treatment (given on day 2) as compared to controls. 

Antiresorptives, particularly bisphosphonates (BP), offer a promising treatment inpediatric bone disease. BP have been successfully used to treat childrenwith osteogenesis imperfecta (OI), secondary osteoporosis, fibrousdysplasia, hypercalcemia. Concerns exist regarding bone mineralizationand bone growth and transient adverse reactions. According to available literature, BP were successfully used in ~1000 children, intravenous pamidronate (PM) being the most frequently used one (>500 children, mostly with OI), followed by alendronate (AL) (~300 patients with OI, secondary osteoporosis, hypercalcemia), risedronate, etidronate, zoledronate, clodronate, olpadronate. OI treatment with BP resulted in an increase in BMD, improved growth, relief from pain, mobility improvement, improved quality of life and a drop in fracture rate There are sparse data comparing oral and i. v. BP. Oral and i. v. BP seem to have a similar effect in children with OI. Daily AL therapy seems to be safe and effective in children with OI, and daily or weekly administration of AL led to increase in BMD in patients with secondary osteoporosis. There is scarcity of randomized, double blind, placebo-controlled or active comparator trials with BP in children. Currently, double-blind, placebo-controlled study with risedronate andactive comparator trial with intravenous zoledronate in children with OI are planned. BP therapy should be used in context of a well-runclinical program with specialist knowledge in the management of pediatric metabolic bone disorders. Other emerging antiresorptive agents include denosumab, glucacon-likepeptide-2 and calcitonin tablets. These drugs are tested in phase III trials in adults. Their applicability to children is likely to be discussed in the coming years. The current KDIGO recommendations on classification or renal osteodystrophy recommend assessment of three areas of bone histology: turnover, mineralization, and volume. While lesions of bone turnover are prevalent in children treated with dialysis, little is know about the prevalence of mineralization defects and their response to therapy with vitamin D sterols and phosphate binders. We evaluated the skeletal mineralization (osteoid thickness (O. Th.) and osteoid maturation time (OMT)) in 207 patients ages 13±1 years treated with maintenance dialysis who were not receiving vitamin D sterol therapy. Serum biochemical markers were: Ca: 9.2±0.1 mg/dl, P: 6.2±0.2 mg/dl, PTH: 660±40 pg/ml, Alk P'tase: 390±21 IU/dl. 53% of patients with high turnover bone disease (95% CI: 43-62%) and 29% (18-41%) of patients with normal or adynamic bone had abnormal skeletal mineralization as reflected by both a prolonged OMT and widened O. Th. Subsequently, a subset of 103 patients underwent treatment with calcitriol and calcium carbonate. While serum PTH levels decreased by 36% (p<0.05) and bone formation rate decreased by 41% (p<0.05) with therapy, there was no change in O. Th or OMT from baseline. Indeed, 67% (55-77%) of patients had abnormal mineralization after therapy. We conclude that mineralization defects are prevalent in children treated with dialysis and are not affected by current therapeutic options. Further studies are needed to determine the pathophysiology and optimal treatment of these defects. Introduction: Clara cell secretory protein (CC16) is a protein synthesized primarily by non-ciliated bronchiolar epithelial cells, the Clara cells. Like other low-molecular size proteins, plasma CC16 is rapidly eliminated by glomerular filtration and reabsorbed by proximal tubular cells. This protein has been rarely studied in the paediatric age. The sensitivity of CC16 in urine was compared to that of b 2-microglobulin (b 2m) and N-acetyl-b-D-glucosaminidase (NAG Conclusions: CC16 is a good marker of the proximal tubular function. CC16 is related better with the urinary b 2m elimination, since both are low-molecular size proteins that are reabsorbed by the proximal tubule.

SD. Kim, BS. Cho Kyunghee University Hospital, Pediatrics, Seoul, South Korea Background: Many studies have demonstrated that ARB prevents renal progression in patients with glomerular nephritis or diabetic nephropathy by inhibition of HMC proliferation and reduce of extracellular matrix expansion and glomerulosclerotic changes. However, the molecular effects of ARB in cultured HMC have not been completely defined. We investigated differential gene expression by ARB treatment on cultured HMC according to time sequence using cDNA chip (Affymetrix).

Methods: MC was grown in DMEM with 10% FBS and then ARB was treated on cultured MC. RNAs of HMC at different time points (4, 8 , and 24 h after ARB treatment and no treatment) were compared using affymetrix cDNA chip. To validate the patterns of gene expression analyzed by the microarrays, some genes were selected and semi-quantitative RT-PCR was performed.

Results: Among genes, humoral immune response, cytokine activity, IL-8 receptor binding, chemotaxis, cell cycle arrest, and morphogenesis associated genes were down-regulated for 4, 8, and 24 h after ARB treatment. They also showed different clustering according to their changing patterns.

Conclusion: The present study demonstrates profile of gene expression as time goes by after ARB treatment on proliferation of human MC. Gene expression by ARB treatment on cultured HMC showed sequential changes. Our results showed that chemotaxis and immune response associated genes were suppressed by ARB treatment on HMC. Further evaluation of individual genes will be conducted to elucidate molecular mechanism. Podocin is the major component of the slit diaphragm, the site responsible for size and charge selectivity of filtration. Mutations in the NPHS2 gene, which encodes podocin can lead to steroidresistant nephrotic syndrome (SRNS). In this work we studied whether genetic changes of podocin might predispose to the development of sporadic non-familial SRNS in childhood. We screened for podocin mutations 50 children (26M/24F; mean age 11.9±0.7 years) with sporadic SRNS and 50 healthy controls. Renal biopsy in SRNS patients revealed mesangial proliferative glomerulonephritis (n=21), focal segmental glomerulosclerosis (FSGS; n=13), membranoproliferative glomerulonephritis (n=13) and membranous nephropathy (n=3). The mean age of onset of SRNS was 8.8±0.7 years. All 8 exons of podocin gene of patients with SRNS and controls were amplified and direct DNA sequencing was performed. There is one novel nonsense heterozygous mutation of c.328 G>T p.87Glu>Stop was identified in the 1 st exon of NPHS2 gene in SRNS child with FSGS who has renal transplantation at the age of 2 years without recurrence of FSGS in her graft. We found one kind of single nucleotide polymorphism c.872+7A>G in the 7 th exon of NPHS2 gene in 6% (3/50) SRNS patients (2 with FSGS; 1 with membranoproliferative glomerulonephritis) and 10% (5/50) children in controls. Allele frequency of this polymorphism of the NPHS2 gene in SRNS patients and controls was not different significantly. Our results indicate that mutation-detected rate in the NPHS2 gene in Russian children with sporadic SRNS was 2%. The low mutation-detected rate and identified polymorphism c.872+7A>G in NPHS2 gene unlikely predispose to the development of sporadic SRNS in Russian children. Further determining the slit diaphragm genetic profile of children with sporadic SRNS is warranted in order to improve disease classification and tailoring of treatment. For diagnose of essential hypertension is necessary except all causes of secondary hypertension (SH). Case: family history of 17-year-old female patient was unremarkable for hypertension, incl. renal diseases. During last 6 months she had often headaches with intermittent vertigo. She was not anywhere examined. At admission on intensive care unit patient had headache, her pulse rate was 130/min, respiratory rate 12/min, BP (right arm) was 220/180 mmHg and the lower extremity BP 225/188 mmHg. Other physical examination was normal, incl neurological exam. Fundoscopy of the eyes did not show any evidence of hypertensive retinopathy. Cardiac ultrasound showed mild left ventricular hypertrophy. Abnormal laboratory parameters (without medication) were: hypokalemia (3.0 mmol/l), metabolic alkalosis (pH 7.48, HCO 3 26.3 mmol/l), low urinary output of sodium (22 mmol) and chloride (<18 mmol), high urinary output of potassium (34 mmol). Renal function tests were normal and no abnormalities were detected by renal ultrasonography, incl. Doppler exam of renal blood flow. By large hormonal analyse were detected high plasma renin activity (PRA; 12.8 ng/ml/hod; n.r. 0.5-1.9) and very mild increased serum aldosterone (Ald; 0.63 nmol/l; n.r. 0-0.60). During the CT renal angiography was found solid mass in the upper part of the left kidney. A partial left nephrectomy was performed and histological exam revealed juxtaglomerular cell tumor (so-called reninoma, RE). After the resection we stopped subsequently patients antihypertensive therapy. In a 3-month follow-up our girl was normotens. RE is a very rare cause of SH. RE typically present during adolescence or young adulthood. This cause of severe SH should be considered along renal artery stenosis in adolescents presenting with secondary hyperaldosteronism or in causes with renin-secreting tumor of non-renal origin. We report our preliminary molecular findings in twelve Turkish cystinosis patients. The patients were 3 to 22 years; male/female ratio was 7: 5. All presented initially with severe failure to thrive, polyuria and polydipsia. Cystinosis was diagnosed at age 1 month to 6 years. Six of the patients reached end stage renal failure at ages ranging from 6.5 to 15 years necessitating renal replacement therapy; 3 are currently on hemodialysis, one is on CAPD, and two were transplanted. While three of remaining 6 have renal Fanconi syndrome with proteinuria, 3 had kidney failure in varying degrees. Molecular analyses involve an initial multiplex PCR, checking for the presence or absence of 57 kb founder deletion, and subsequent sequencing of the 9 coding exons of CTNS. Interestingly, none of the 12 nephropathic cystinosis patients carried the 57 kb deletion. Instead, one patient had a new homozygous 10 kb deletion of exons 4 to 9 of CTNS. One patient was homozygous for a known 4 bp deletion in exon 3, i.e., c.357del GACT. Two patients were homozygous for new missense mutations in exons 7 and 9, i.e., c.451G>A (R151G) and c.518A>G (Y173C), respectively. The most common mutation in our Turkish patients was a new exonic splice site mutation in exon 9, i.e., c.681G>A (E227E). Of 24 alleles studied, 7 carried this mutation, which is expected to disrupt proper splicing. Two patients were compound heterozygous for one of the above-mentioned mutations and a known missense mutation in exon 12, i.e., c.1015G>A (G339R).

In two patients, we could not find any disease-causing mutation; in two patients, we could find only one disease-causing mutation. In summary, cystinosis patients of Turkish ancestry show CTNS mutations different from those of Western European patients. These findings will be of relevance for molecular-based screening and diagnostic methods for cystinosis.

Introduction: The association of hypertension with Bell's palsy in adults has been reported from 4-11%, but there is few data in children. The presence of Bell's palsy in children requires a complete evaluation for hypertension, solid tumors, leukemia, neurofibroma, and trauma. Hypertensive children usually present with clinical manifestations of underlying disease, but with substantial elevation, symptoms of hypertension develop. Although headache, dizziness, blurred vision and seizure are common neurologic symptoms of hypertension, but facial paralysis is not a wellrecognized presenting feature of hypertension in children.

Case report: This paper describes two severely hypertensive children who referred to Children's Hospital of Tabriz with periferal hemifacial nerve paresis and initial diagnosis of Bell's palsy. Case 1: A 12 years old girl who admitted with blood pressure of 230/120 mmHg on admission. Renal ultrasound study revealed left small size kidney and renal scintigraphy followed by angiography confirmed renovascular hypertension. Case 2: A 5 years old boy with blood pressure of 180/100 mmHg on admission. Sonography of kidneys was normal except for a small size (4 mm) stone in left kidney. Renal scintigraphy and angiography were normal. All other evaluations for etiology of hypertension including cardiac and endocrine investigations were negative. Treatment of hypertension with antihypertensive drugs resulted in complete recovery of facial paresis in both cases within 3-4 months.

Conclusion: Unilateral peripheral facial nerve paresis is a rare presentation of hypertension in children. Unawareness of this presentation may result in delay in diagnosis of hypertension which may increase further with steroid therapy for Bell's palsy. To uncover the frequency and the spectrum of NPHS2 mutations in Egyptian children with non familial steroid-resistant nephrotic syndrome (SRNS), 16 patients were screened by PCR-singlestrand confirmation polymorphism analysis of NPHS2 gene followed by direct sequencing. NPHS2 mutations were evident in 5 patients (31.3%) who were bearing five novel mutations including two frame shift mutations (713-714insG and 132-133insG), two missense mutations (556A>C and 647T>A) and a silent mutation (408A>T). There were no phenotypic or histological characteristics of patients bearing NPHS2 mutations, apart from the earlier onset of the disease, compared to those who were not bearing mutations. In conclusion, NPHS2 mutations are prevalent in Egyptian children with non-familial SRNS and this may in part explain the less favorable prognosis reported in these patients. , which is an inherited systemic disease of connective tissue primarily affecting the skin, retina, and cardiovascular system, also leads to RVH. These symptoms of PXE are usually apparent in adulthood and rarely observed in children. Here, we describe a very rare pediatric case of RVH caused by PXE.

Case report: A 6-year-old boy was noticed to have severe hypertension (183/128 mmHg) when he was admitted to our hospital for an operation for exotropia. He had no previous or family history of PXE or hypertension. Laboratory examination showed that plasma renin (517.0 pg/ml) and aldosterone (71.3 ng/dl) concentrations were markedly elevated. His systolic and diastolic blood pressure (BP) decreased 12.7% and 22.2% from baseline after administration of captopril, respectively. A computerized tomographic scan of his abdomen showed multiple calcified vessels in kidneys and spleen. Yellowish papules on the bilateral axillary regions and inguinal area were detected. Characteristic histological changes of PXE such as elastic fiber mineralization and calcification were noticed in the biopsy of affected skin lesions. Conclusion: PXE is characterized clinically by high heterogeneity in the age of onset and extent and severity of organ system involvement. Although its symptoms usually appear in the second or third decade of life, gastrointestinal bleeding and acute myocardial infarction have been reported in childhood. We should also consider PXE as one of the causes of RVH in children, because its prognosis depends largely on the extent of extracutaneous organ involvement. The CLCNKB gene is rarely reported as having a large deletion mutation, but all cases reported previously were large homozygous deletions and a large heterozygous deletion is impossible to detect by direct sequencing. Patients and Methods: This report concerns a genetic analysis of 5 Japanese patients with type III BS. To identify the mutations in the CLCNKB gene, we used polymerase chain reaction (PCR) and direct sequencing to investigate all exons and exon-intron boundaries in the patients and their family members. To detect large heterozygous deletion mutations of the CLCNKB gene, we conducted semi-quantitative PCR amplification using capillary electrophoresis.

Results: Four mutations were identified, comprising 1 novel 2 bp deletion mutation (c.1334_1335delCT), an entire heterozygous deletion and a heterozygous deletion mutation of exon 1 and 2 of the CLCNKB gene. The nonsense mutation W610X in the CLCNKB gene was detected in all patients (2 of them were homozygous and 3 were heterozygous) and this finding indicates that this nonsense mutation is likely to constitute a founder effect in Japan. Two patients had large heterozygous deletion of the CLCNKB gene, which was proved by semi-quantitative PCR amplification.

Conclusions: Capillary electrophoresis is a new method and extremely useful for detecting large heterozygous deletions, and should be employed to examine type III BS cases in whom only a heterozygous mutation has been detected by direct sequencing. Obesity defined as body mass index (BMI) above 95 th percentile for age and gender is regarded as a risk factor for cardiovascular (cv) target organ damage (TOD) in children and adults with PH. However, when using percentile-based definition of obesity one may miss children at risk of cv complications. The aim of the study was to compare sensitivity of traditional definition of obesity (BMI>95 th pc) and BMI thresholds (tBMI) for cv complications described by Katzmarzyk et al. (2004) Majority of children with idiopathic nephrotic syndrome (frequent relapsers, steroid dependent and steroid resistant) require adjunctive therapy. The response to cyclophosphamide (CP) in these children is variable and difficult to predict. There may be an effect of polymorphic expression of GST on the remission with CP. In this study, we have tried to evaluate the correlation of GST polymorphism and response to CP therapy in these children We studied GST polymorphism in 73 consecutive children (54 males, 19 females) with steroid sensitive (n=44) and steroid resistant (n=29) nephrotic syndrome, receiving CP therapy. We evaluated the inter-relationships between GSTM1, GSTT1, and GSTP1 genotypes and correlated it with the response to CP therapy in these children. The mean age of onset was 5.2±4.4 years. Out of 73 children, 67% children responded to cyclophosphamide therapy. The null genotype of GSTM1 and GSTT1 was observed in 39.7% and 64.4% respectively while Val105 genotype of GSTP1 was seen in 22% children. There was no significant correlation among the various individual genotypic combinations. However, a trend was seen towards remission in children with a combination of GSTP1 polymorphism with GSTT1 null genotype (p=0.08) or combination of GSTP1 polymorphism with GSTM1 wild type genotype (p=0.0885) Another important finding in our study was that there was a significantly higher frequency of Val105 allele of GSTP1 in responders to cyclophosphamide as compared to nonresponders (p=0.01). The results indicate that the presence of the Val105 allele correlates with the response to cyclophosphamide in these children. GST gene polymorphism may be a significant therapeutic tool in the management of children with idiopathic nephrotic syndrome receiving therapy. Objectives of Study: Primary vesicoureteral reflux (VUR) is a common pediatric disease that may lead to reflux nephropathy and end-stage renal disease. The renin-angiotensin system (RAS) was proposed to be associated with primary VUR. The objective of this study was to investigate whether the gene polymorphisms of the RAS are involved in primary VUR and correlation with the severity of VUR in Taiwanese children. Methods: We studied the angiotensin II type 2 receptor (AT2R) C3123A gene polymorphism for association with susceptibility to primary VUR and disease severity in 100 VUR children and 60 healthy controls. Fifty four of the 100 VUR patients had low-grade VUR (grade I-III) and 46 had high-grade VUR (grade IV and V). To analyze the polymorphisms in the C3123A of AT2R gene, the SNP genotyping assay were performed. The genotypic frequency and allele frequency for four RAS genes were analyzed to detect the correlation between the patients with mild, severe VUR, and healthy control. Results: We found that the C3123A of AT2R gene was associated with the development and severity of VUR. Significantly higher C and lower A allele frequencies were presented in VUR patients (C allele 0.67 and A allele 0.33) compared with controls (C allele 0.56 and A allele 0.44, P<0.005). The similar results were observed in both mild (C allele 0.73 and A allele 0.27) and severe (C allele 0.62 and A allele 0.38) VUR compared with controls (P<0.005). The CC genotype was higher in VUR patients compared with controls (P<0.005).

Conclusions: AT2R C3123A gene polymorphism was associated with the development and the severity of VUR in Taiwanese children. It raises the possibility to utilize the genotype of AT2R as a risk factor to evaluate the development and severity of primary VUR. Results: Stone analysis led to diagnosis of cystinuria in 12 patients (1% of all), but only 5 were children (1.4% of the paediatric stone patients). Age at diagnosis in three patients was 17-30 years and in four 30-49 years. Time from first manifestation (pain 7x, gross haematuria 3x, urinary retention 2x, UTI 4x) until diagnosis was 0-2 years in seven, 5-10 in three and even 34 and 39 years in two. Renal function was impaired in 1 patient (CKD stage II). The urinary cystine test was positive in all 9 patients with cystine stones examined, but was negative in 2 family members thus excluding cystinuria in them. Family history of urinary stones was positive in two; the brother of one had died of renal failure due to bilateral urolithiasis. Conclusions: Delays in diagnosis of cystinuria in Armenia are unacceptable. Production of tablets containing nickel/dithionite which is non-toxic in contrast to Brand test (cyanide/nitroprusside) is planned and could allow screening of all patients with stones of unknown origin. Background: Classically, childhood hypertension has always been recognized as secondary and frequently demanded an exhaustive etiological investigation. However, in the last two decades, many studies have been shown that pediatric patients also present primary hypertension and, sometimes, the adult disease probably begins during childhood. The aim of this study was to analyze a cohort of patients followed-up at a single tertiary Unit (Belo Horizonte, Brazil). Methods: In this retrospective cohort study, the records of 220 diagnosed with arterial and followed at our Unit between 1994 and 2004 were analized. A data base was used for statistical analysis.

Results: Of 220 patients, 53.2% were male and 46.8% female. The distribution of patients according to the age at diagnosis was: 0-1.99 years, 3(1.4%), 2 yr-6.99 yr, 51 (23.2%), 7 yr-11.99 yr, 55 (25%), and 12 yr, 111 (50.4%). The causes for hypertension were: renal diseases in 172 (78%), primary hypertension in 33 (15%), renovascular disease in 9 (4%) and ohers in 6 patients (3%). The comparison between primary hypertensive subjects and patients with renal diseases showed that, although blood pressure was similar at admission, a better control was achieved in the first group (p<0.05). The frequency of overweight and/or obesity was higher in primary than in secondary hypertension ( Nephrnophthisis (NPHP) is a very rare cause of CRF in Korea. Identification of five genes mutated in NPHP subtypes 1-5 has linked the pathogenesis of NPHP. Ten percent of affected individuals have retinitis pigmentosa, constituting the Senior-Löken syndrome. We experienced juvenile-onset CRF with Leber's amaurosis in two sibilings. Case 1: A 10-year-old boy presented with pale appearance. He had severe renal impairment and visual disturbance, but no symptom of polyuria and polydipsia. His past annual school screening urinalysis was normal. His growth and development were normal except opthalmological findings and pallor. Case 2: His 14-years-old sister also had a visual disturbance and was found to have CRF. There was no specific problem during perinatal period. Opthalmologic findings were similar to her brother's. NPHP1 and 5 on chromosome 2q13 was analyzed by direct sequencing. Sequencing of mitochondrial DNA-Mbol digestion for 14484 mutation was analyzed by PCR-Sequencing and RFLP. Electroretinogram revealed a decreased in amplitude of a and b waves. On the kidney biopsy, some of glomeruli were globally sclerotic. Remaining showed no cellular proliferation or capillary wall thickening. Interstitium was diffusely fibrotic and in which were scattered lymphocytes. Most tubules were preserved well but a few dilated tubules were intermingled. No positive reaction for immunoglobulines or complements in IF. By EM, tubular membranes showed thickening, splitting and disintegration. NPHP1 and 5 genes were not identified. There was no transition mutation at mitochondrial DNA nt.11778, 3480, 14484, 15257. Late-onset Senior-Löken syndrome were diagnosed in these cases even though there were no polyuria and polydipsia of initial symptoms of NPHP and NPHP1 and 5 were not identified. We need to identify other known or novel mutation genes. Nail-patella syndrome (NPS) is an autosomal dominant disease characterized by classic tetrad of dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. some patients manifest nephropathy and adult-onset glaucoma. NPS is associated with mutations in the LMXIB gene. There is marked inter-and intrafamilial variability in the phenotypes. In this study, phenotype-genotype correlation was analyzed in 7 unrelated Korean children with NPS. The probands were 3 boys and 4 girls. They manifested dysplastic nails (7/7, 100%), absent or hypoplastic patellae (6/7, 86%), elbow dysplasia (4/7, 57%), iliac horns (3/7, 43%) and nephropathy (2/7, 29%) . Four missense mutations/2 in the LIM-B domain (H114Q and L127P) and 2 in the homeodomain (R200Q and A213P)/and 1 frame-shifting deletion (c,680delA) were identified in the LMXIB Gene.R200Q and A2123P are known to be common mutations, and R200Q was detected in 3 patients in this study. Autosomal dominant inheritance was identified in 3 patients by phenotype and genotype analysis of the family members and in 2 patients by phenotype analysis only. Remaining 1 patient had de novo R200Q mutation. One patient and her mother with R200Q mutation developed nephrotic syndrome, which progressed to end-stage renal disease (ESRD). Another patient with H114Q mutation had asymptomatic proteinuria with microscopic hematuria, and her father had ESRD. Galucoma was not detected in any patients or family members affected. There were inter-and intrafamilial variability of the phenotypes, but no genotype-phenotype correlation was identified. This is the first study to characterize mutations in the LMX1B gene in Korean patients with NPS. R200Q is a common mutation in Korean, also. The mechanism underlying the phenotypic variations and predisposing factors to the development nephropathy remain unknown. The pathological mechanism which would be responsible for higher production of digitalis similar compounds in essential arterial hypertension (AH), would be a genetically defect kidney, which causes difficulty in Na + excretion. Higher intake of salts can be an etiological factor inessential AH only patients with inherited abnormalities of thetransport mechanisms in the cell membrane.The objective of the studywas to establish the incidence and type of AH and frequency of genetic factor in the investigated population of 3000 school children (age 7-16years). In children with essential and borderline AH we evaluated the activity of erythrocyte membrane Na+, K+-ATPase in the presence ofvarying ATP concentrations. ATP, ADP and AMP levels and lipid peroxides (as TBARS) in the erythrocytes and TBARS in plasma were measured. Our data have shown that the prevalence of AH is lowest in 7-8 years oldchildren, while it is the highest in 15-16 years oldchildren. Essential AH was established in 11 (0.36%) and borderline in 17 (0.56%) children. Genetic factor were found in 54.5% of children with essential AH and in 60.4% of children with borderline AH. But, statistical analyses of the first and second degree relatives of children with essential and borderline AH suggested normal prevalence of hypertension. ATP, ADP and AMP levels, as well as, lipid peroxides were not significantly altered compared to healthy children. Kinetic profileof erythrocyte plasma membrane Na+, K+-ATPase activity revealed the presence of noncompetitive (allosteric) inhibition of enzyme activityin the children with essential and borderline AH. The differences in the kinetic properties of Na+, K+-ATPase between two investigated groups of children suggested that this dynamic model could be used as potential biological marker for early diagnosis and differentiation of these two type of AH. Majority of these patients were obese and with increasing body weight nighttime hypertension became prominent in these patients. Objectives: It has been shown that weight gain is directly related to increase inblood pressure. The objective of this study was to analyze the frequency of overweight/obesity in children/adolescents with primary hypertension (PH) and the relationship between the overweight/obesityand the stage of hypertension (H). Methods: We analyzed the data of 113 patients aged 10-17.5 years (M 65; F 48) diagnosed with primary hypertension. Overweight/obesity was defined asperc. of BMI -85/95 c. The stage of hypertension was determined according to The 4 th Report on the Diagnosis, Evaluation,and Treatment of High Blood Pressure in Children and Adolescents of the NHLBI Working Group. Results: Out of 113 pts, prehypertension was found in 10 pts (8.9%), Stage I H in 30 (26.5%) and stage II H in 73 pts (64.6%). Stage II H was more frequentin boys (69% vs. 58% in girls). Combined systolic/diastolic H was found most frequently, in 58 pts (51.3%), isolated elevation in systolic blood pressure (BP) was found in 47 pts (41.6%), while only 8 pts (7.1%) had isolated elevation in diastolic BP. Sixty-one pts (53.98%) were found overweight/obese; of which 33 (54.1%) above 95c BMI. Theobese children were predominantly found to have stage II H: 84.8% ofthe obese children. None of the obese children had prehypertension. Contrary to the general perception, boys were found more frequently overweight/obese (67.2% boys vs. 32.8% girls). Conclusion: Our data shows that stage II PH is not rare also in theteen-age group. Frequently it is accompanied with overweight/obesity, especially in boys. We can conclude that the roots of PH in the adultage are already set from the childhood. Our efforts should focus onearly diagnosis of PH and include prevention of obesity as the possible contributing factor for the development of PH. Objectives of study: Alport syndrome (AS) is a progressive renal disease characterized by hematuria, progressive renal failure, high-tone sensorineural hearingloss and ocular lesions. Xlinked dominant Alport syndrome (XLAS) isthe major inheritance form, accounting for almost 80% of the cases, caused by mutations in COL4A5 genes. There are no good cures available for AS at present, but there are some patients who requestfor prenatal diagnosis and genetic counciling. This study performed thefirst prenatal diagnosis in Chinese AS family. Methods: The entire coding sequence of COL4A5 mRNA of peripheral blood lymphocytes was amplified using nest PCR to screen mutations in a ChineseXLAS family. Mutation analysis of the fetus was performed on both cDNA-based level and DNA-based level of amniocytes. Fetus sex was determined by PCR amplification of SRY as well as karyotypes analysis. Maternal cells contamination was excluded by linkage analysis.

Results: Mutation screen showed that there was a G to A substitution at position 4271 in exon 46 of COL4A5 gene (c.G4271A), it was subsequently confirmed at genomic DNA level by PCR amplification of exon 46 of COL4A5gene. The mutation was identified in the index case, family members aswell as the pregnant lady. The prenatal diagnosis showed that fetus didnot carry the same mutation as the mother detected by both cDNA-basedand DNA-based mutation analysis. PCR amplification product of SRYas well as karyotypes analysis revealed a male fetus. Linkage analysis of the three X chromosome markers showed that there was no contamination of maternal cells in amniocytes.

Conclusion: After mutation identification of COL4A5gene in a large Chinese AS family, a successfully prenatal diagnosis was performed in one of the female members in this family based on both cDNA as well as genomic DNA level of amniocytes. Objectives of study: Alport syndrome (AS) is a clinical and genetic heterogenousdisease. Autosomal recessive AS (ARAS) is caused by mutations in COL4A3 and COL4A4 genes, accounting for 10% of the cases. Thin glomerular basement membrane nephropathy (TBMN), is also caused by mutations in COL4A3 and COL4A4genes, inherited as an autosomal dominant trait. Differentiation between early stages of ARAS and TBMN may be difficult in clinic, itdepends on gene mutation analysis of COL4A3 or COL4A4. Methods: The whole entire coding regions of COL4A3 and COL4A4 mRNA of peripheral blood lymphocytes were analyzed using reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing to screen mutations in three Chinese ARAS families, the corresponding exon with flanking intronic sequence was further amplified to confirm the abnormality.

Results: Both the entire coding regions of COL4A3 and COL4A4 mRNA were successfully amplified and completely sequenced by seven overlapping PCR products, respectively. Results showed that there were 10 variations of COL4A3 and 4 variations of COL4A4, respectively. Among the 10 variations of COL4A3,three were SNP reported previously, four were new SNP, one nonsense mutation, one small insertions and one splicing mutation, the latter three were the pathogenic mutations for the three families, respectively. All the four variations of COL4A4 were SNP reported previously.

We concluded that RT-PCR and direct sequencing using peripheral blood lymphocytes RNA is a practical, sensitive and feasible approach for analysis COL4A3 and COL4A4 gene variants in autosomal recessive Alport syndrome patients, which offers a useful, inexpensive and timesaving approach for systematic gene analysis in patients with ARAS. Objectives of study: Gitelman syndrome (GS) is an autosomal recessive tubular disorder characterized by metabolic alkalosis, hypokalemia, hypomagnesemia and hypocalciuria. The majority of GS patients carry inactivating mutations of the SLC12A3 gene encoding the sodiumchloride cotransporter located in the distal convoluted tubule. This study aimed to detect mutations in a Chinese family with GS. Methods: Two brothers presenting muscle weakness, hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria were clinically diagnosed as Gitelman syndrome. The two brothers, as well as their healthy brother and parents, were detected for mutations in SLC12A3 gene by direct PCR for each exon and then sequencing on genomic DNA extracted from peripheral blood cells.

Results: The two patients were found to have the same compound heterozygous mutations (c.917C>T and IVS 14-8T>C) in the SLC12A3 gene. The two mutations were also detected in paternal and maternal genomic DNA, respectively. The unaffected brother had one mutation (c.917C>T) only.

Conclusion: A novel compound heterozygous mutation on the SLC12A3 gene was revealed in a Chinese family with GS.

The Objective: To determine the clinical value of ambulatory blood pressure monitoring (ABPM) in pediatric kidney disease. Methods: 83 patients with common kidney diseases aged from 5-16 yrs were enrolled. 24-hour ABP were performed by Welch Allyn ABPM6100. The number of cases whose Ccr>90mmol/L/1.73 m 2 , Ccr 60-89 mmol/L/1.73 m 2 , Ccr 30-59 mmol/L/1.73 m 2 , Ccr 15-29 mmol/L/1.73 m 2 and Ccr<15 mmol/L/1.73 m 2 is 64, 4, 5, 1 and 9, respectively. Seven patients only took fosinoprilto control blood pressure did ABPM again more than one weeks after therapy. 1141 healthy children performed in German in 1997 was used asthe normal data. Casual BP was measured by sphygmomanometer. 23 children took echocardiography to calculate left ventricular mass index (LVMI).

Results: The incidence of nocturnal hypertension was significantly higher than that of diurnal hypertension (P<0.001).Theincidence of non-dipper in 83 children with kidney disease was 68.7%. Nocturnal dipping rate in the patients was significantly lower than that in the healthy children (P<0.01). The incidence of masked hypertension and white coat hypertension inchildren with kidney disease were 3.6% and 9.1% respectively. Nocturnal systolic and diastolic dipping rate of the children with lupus nephritis and acute glomerulonephritis were lower than those of the children with Henoch-Schönlein purpura nephritis (P<0.05). LVMI hadpositive correlation with 24-hour diastolic blood pressure load (r=0.414, P=0.036), but it had no correlation with casual BP. After taking fosipril, 24-h, diurnal and nocturnal average ABP decreased significantly (P<0.05). Nocturnal dipping rate increased, but did not reach statistical difference (P>0.05).

Conclusions: ABPM was an effective tool for diagnosis and management of hypertension in childhood with kidney disease.

Identification of 6 Novel Mutations in the COL4A5 Gene of Japanese Patients with X-linked Alport Syndrome Background: Alport syndrome consists of nephritis, often progressing to renalfailure, and sensorineural hearing loss. X-linked phenotype (OMIM#301050) is the result of mutation in the gene for the alpha-5 chain of collagen IV (COL4A5). Objectives of study: To find mutations causing X-linked Alport syndrome in Japanese patients. Patients and Methods: Diagnosis criteria of Alport syndrome were proteinuria, familial history of renal failure andchanges of GBM in electron microscopy. To identify the mutations in the COL4A5 gene.

Results: For the time being we finished genetic analysis of 8 patients with suspected X-linked Alport syndrome, 6 males and 2 females. We identified mutations in 7 of 8 patients; 6 of them were novel mutations. They comprise: 2 nonsense mutations, 2 missense mutations and 3 mutations of splicing acceptor site resulting in exon skipping or truncation, and establishing of premature stop codon. In previous reports of X-linked Alport syndrome, mutation detection rate was around 60%.

The present study provides a detection rate of 87.5%, although our number of examined cases is limited.

Conclusions: Direct sequencing of RT-PCR and PCR products is efficient method of finding mutations in COL4A5 gene. We found mutations in high percentage of investigated patients. Objectives of study: To make a genetic diagnosis of juvenile nephronophthisis for a Chinese boy.

Methods: Analyze the presentation, family history, laboratory investigations, and histological features of a patient suspected of juvenile nephronophthisis, make a clinical diagnosis. To confirm the diagnosis on genetic level by PCR amplification of satellite markers located within the known homologous deletion of NPHP1,including del-2, del-9, del-16, del-5-(5)2, del-10 and markers outside the deletions (RanBP11/12 and D2S1896)as control.

Results: The boy was nine years old, he was admitted becauseof renal failure for 6 months. This case manifested by school age, negligible onset, anemia, polyuria, renal failure at 9 years old,without hypertension and abnormal urine analysis. His sister presented with anemia at 1 year old, and died of uremia at 6 years old.Laboratory investigations showed no proteinuria and hematuria. Thekidney size is normal, and the cortical medullary boundary is obscure.The histological features consist of the disintegration of tubularbasement membrane, the atrophy and dilation of renal tubules, theinterstitial cell infiltration and fibrosis. He was suspected asjuvenile nephronophthisis. By PCR amplification, we found the missingof the satellite markers of del-2, del-9, del-5-(5)2 and del-10, which indicate that there is the common large homologous deletion (250kb) in the child's NPHP1. Conclusions: Nephronophthisis is the major hereditary cause ofchronic renal failure. The boy was suspected of nephronophthisis because of chronic renal failure, family history, normal kidney sizeand hitological features. According to the age of renal failure, he was suspected as juvenile nephronophthisis. The diagnosis was confirmed by gene analysis. It is the first juvenile nephronophthisis case for Chinese confirmed by gene analysis. Cutaneous small-vessel vasculitis is a rare condition in children and is commonly associated with a wide spectrum of systemic inflammatory conditions, malignancies, infections or drug hypersensitivities. Enalapril is anangiotensin-converting enzyme inhibitor, commonly used for the treatment of hypertension. Cutaneous vasculitis due to enalapril has very rarely been reported and only with adults. We report a case of an 8-yea-old boy presented with a pruritic eruptionover his lower legs that started 6 hours after he had initiated treatment with enalapril at a dose of 0.5 mg/kg/daily. He had a history of hypertension due to a shrieked right kidney since infancy and he wason treatment with nifedipine and propranolol for the last three years. This medication was discontinued because it was ineffective, the day before initiation of enalapril. Clinical examination revealed palpable purpuric lesions involving lower legs and ankles. He was otherwise well. A skin biopsy of the lesions showed leucocytoclastic vasculitis of small vessels. Abnormal investigations were elevated C-reactive protein, ESR and leucocytosis. Further laboratory tests including creatinine, liver function tests, urineanalysis, antinuclear antibody, cryoglobulins, viral serology, complement levels, were normal or negative. Enalapril was discontinued and he was started oral prednizolone and ceterizine over the next ten days. The skin eruption regressed rapidly. Cutaneous vasculitis induced by enalapril is a rare adverse effect and it is essential a prompt recognition and withdraw of the suspicious drug. Objectives of study: Barttin, the gene product of the BSND gene involved in Bartter's syndrome with sensorineural deafness, is an essential b-subunit for ClC-Ka and ClC-Kb chloride channels, and it is expressed in the kidney as well as in the inner ear. One patient affected by deafness and renal Bartter phenotype without BSND mutations has been previously reported with simultaneous mutations in both CLCNKB (responsible for classic Bartter syndrome) and CLCNKA genes. We report here on a new case of a 6-months-old boy presenting such a disease. A severe polyhydramnios was detected during the pregnancy. He presented also polyuria, growth retardation, nephrocalcinosis and sensorineural deafness. Laboratory studies revealed metabolic alkalosis (plasma HCO3 47,7 mmol/L), hypokalemia (2,4 mmol/L), hypercalcuria (CaU/CrU 1,6 mg/mg) and elevated plasma renin (320 pg/ml). The aim of the study was to identify the cause of the severe renal salt wasting and sensorineural deafness in this patient. Methods: DNA sequencing analysis was performed on the BSND, CLCNKB, and CLCNKA genes. Results: No mutation was detected in the BSND gene. We identified a reciprocal partial homozygous deletion of exons 1-6 for the CLCNKB gene and theloss of exons 7-19 for the CLCNKA gene.

Conclusions: The disruption of both ClC-Ka and ClC-Kb chloride channels leads to a syndrome clinically not distinguishable from BSND, characterized by severe salt wasting and deafness. This digenic disorder is due to simultaneous mutations on the two genes CLCNKA and CLCNKB respectively. The tight topology of the highly homologous CLCNKA genemight predispose to an unequal crossing over leading to partial orcomplete deletions of the CLCNKB gene. We hypothesize that thischimaeric resulting gene interferes with the correct function of both the channels ClC-Ka and ClC-Kb, and leads to a BSND-like phenotype. Familiary hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a nautosomal recessive tubular disorder that is frequently associated with progressive renal failure. Mutations in CLDN16 which encodes the renal tight junction protein paracellin-1 were identified as the underlying genetic defect. In this work we present a Gipsy family with FHHNC in which the mother and daughter both showed homozygous mutations in the CLDN16 gene. A three-year-old girl was investigated after acute pyelonephritis and was found to have medullary nephrocalcinosis, hypomagnesemia (0,5 mmol/l), hypercalciuria (10,5 mg/kg/d), hypermagnesuria (FEMg 15%) and incomplete distal renal tubular acidosis. Her renal function was normal. Her mother demonstrated also bilateral medullary nephrocalcinosis, hypomagnesemia (0.2 mmol/l) with high FEMg (86%), moderate renal failure (creatinine 234 umol/l) and high iPTH levels (398 pg/ml). As a child she had afebrile seizures, but serum Mg levelwas not measured. Index patient's uncle had history of recurrent passage of calculi in childhood, bilateral medullary nephrocalcinosis, normocalcemic hypercalciuria but his serum Mg was not determined. He developed obstructive uropathy due to impaction of the calculus in urethra and eventually progressed to terminal uremia and later was transplanted. Mutational analysis confirmed that the index case, motherand uncle were homozygous for the common mutation in the CLDN16gene (Leu 151 Phe), while the father was heterozygous. We present a new family from Macedonia with FHHNC with unusual presentation over two generation. Mutational analysis confirmed also the diagnosis of FHHNC in the uncle although as a child he was considered to have idiopathic hypercalciuria. Thus, serum Mg should be routinely checked in children with nephrolithiasis/nephrocalcinosis.

M. Pan ' czyk-Tomaszewska, J. S ' ladowska, J. So l /tyski, M. Roszkowska-Blaim

Arterial hypertension is one of the complications of reflux nephropathy. The aim of the study was to assess the risk factors of arterial hypertension in children with primary vesicoureteric reflux (VUR). We studied 150 children aged from 4 to18 years mean 9±3.3, 82 with unilateral and 68 with bilateral VUR. In all children ambulatory blood pressure monitoring (ABPM) and 99m Tc DMSA renal scanning (DMSA) were performed and Z score body mass index (Z-score BMI) were calculated.

The following criteria were examined as predictive risk factors: age, gender, age at diagnosis andat resolution of VUR, period between diagnosis and resolution of VUR,grade of VUR, type of VUR (unilateral or bilateral), treatment modality (medical, surgical), Z-score BMI, grade of DMSA and birth weight.

Results: I grade of DMSA scan was diagnosed in 27 children, IIgrade in 85, III grade in 31 and IV in 7 patients. Hypertension (HP) was diagnosed in 20 children (13%). The mean value of Z-score BMI in children with hypertension was significantly higher in comparison withchildren with normal blood pressure (0.043±0.21 and 0.74±0.86). The multivariate discriminate analysis showed that Zscore BMI and grades of DMSA scars were significant risk factors for developing arterial hypertension in children with VUR. Both parameters had the same influence on development of hypertension (standardized coefficient of discriminate analysis 0,748 and 0,736 respectively).

Conclusion: The development of hypertension in children with VUR is associated with higher BMI and higher grades of renal scars in DMSA scan. Grange syndrome comprises arterial stenoses with hypertension, brachy syndactyly, bone fragility, learning disability, and cardiac defects and it has been reported in the members of two families up to now. We report here a 14-year-old boy with hypertension, multiple arterial stenoses, microcephaly and brachysyndactyly. Severe hypertension (200/120 mmHg) was detected on his routine control for acute rheumatic carditis and he was hospitalised for investigation. He had no complaints. His parents were first degree relatives. His physical examination revealed microcephaly, bilateral brachysyndactyly between the forth and the fifth fingers of hands and the second and the third fingers of feet. Complete blood count, electrolytes, renal, thyroid, and hepatic functions and acute phase reactants were all in normal limits. Echocardiography showed aortic and mitral insufficiency and left ventricular hypertrophy. Renal and cerebral magnetic resonance angiographies demonstrated stenoses at bilateral renal, internal carotid, superior cerebral and posterior cerebellar arteries. Association of hypertension with microcephaly and finger abnormalities and multiple arterial stenosis suggested Grange syndrome. Chromosomal analysis showed 46 XY karyotype. Hypertension persisted despite triple antihypertensive agents and percutaneous renal angioplasty was performed leading to a reduction of antihypertensive medication. With this case report we wanted to remind the recognition of this extremely rare syndrome in a hypertensive child with multiple morphological abnormalities and percutaneous angioplasty as a treatment modality in cases with persistent severe hypertension. Hypertension is usually indicative of an underlying disease process in children. The combination of severe hypertension with hyponatremia is called hyponatremic hypertensive syndrome (HHS). In this report we present a case of HHS. The boy was referred to our hospital at the age of 7 years old with generalized tonic clonic convulsion. His past history was insignificant and positive findins of the patients were as follows: hypertension (170/115 mm/hg), agressive behaviors after convulsive period, metabolic alkalozis (blood gases, pH: 7,51, HCO 3 : 24,8, PCO 2 : 27,3), hypocloremia (87 mEq/L), hypokalemia (3 mEq/L), hyponatremia (123 mEq/L), low urine density, polyuria and high serum aldosterone levels (1000 pg/ml, range: 20-240). The serum renin, cortisol, tyroid and antidiuretic hormones were within normal range. Abdominal color Doppler ultrasound were revealed double renal arteries in both kindneys. Cranial and abdominal tomography examinations and cebrospinal-fluid examination were normal. The diagnosis of HHS was suggested based on these clinical and laboratory findins and therapy of nifedipine was started. The arterial pressure improved with this therapy. In HSS due to renal ischemia, activation of renin angiotensin system which induce pressure natriuresis and thus, thence hyponatremia. We think that presence of renal arterial anomaly might be a cause of an ischemic condition and activation of renin-angiotensin-aldosterone system in our patient. Also, activation of aldosterone could enhance with hyponatremia and it could be suppressed of renin secretion in our patient. [Hadtstein et al. Hypertension 2004] . The aim of this study was to analyze whether children with renal scars have altered rhythms of mean arterial pressure (MAP) and heart rate (HR). Study design: Ambulatory 24-hour blood pressure profiles of 61 untreated patients with renal scars associated with recurrent urinary tract infections and VUR were investigated and compared to 938 healthy controls.

Results: Pre-pubertal, but not pubertal patients with renal scars displayed a number of significant differences to controls. Before puberty, the MESORs of MAP and HR were significantly elevated, and the peak-trough difference of the 24 h curve was blunted by 7.5 mm Hg for MAP and 7.8 bpm for HR. The amplitudes of 24 h and 8h MAP rhythms were blunted by 2.0 and 1.5 mmHg, and those of 24 h and 12h HR rhythms by 1.9 and 1.2 bpm (all p<0.05). Pubertal patients did not display any abnormalities of BP or HR rhythms. We did not find any correlations of the degree of renal scarring, BMI or GFR with the abnormalities in cardiovascular rhythms. Conclusion: In summary, pre-pubertal children with renal scarring due to VUR show blunted circadian and ultradian rhythms of BP and HR. This phenomenon may reflect subtle alterations of autonomous nervous signaling in children with damaged kidneys; it remains to be addressed whether such abnormalities constitute an independent cardiovascular risk factor. Mutations in the EYA1 gene are associated with BOR/BO syndrome and rarely with an isolated renal phenotype. We present a family from Macedonia displaying a novel EYA1 gene mutation. A six-year-old female was found to have bilateral grade III vesicoureteral reflux (VUR) after an episode of acute pyelonephritis. Mutational analysis detected a novel EYA1 gene mutation [an inframe 3bp deletion (c.4_6delTTG), resulting in L2del of EYA1A]. She had no clinical stigmata for BOR/BO syndrome. The paternal grandmother died due to end stage renal failure. All first grade relatives underwent detailed physical and ophtalmological examination, audiometry, ultrasound screening of the urinary tract and mutational analysis of the EYA1 gene. The father and older sister were mutation carriers and both had normal ultrasound findings. The physical examination did not reveal abnormalities suggestive for BOR/BO syndrome, except the sister had esotropia/ hypermetropia and horizontal nystagmus. The male sibling was found to have mild hydronephrosis on the left side. He was not a mutation carrier and cystographic study was not performed at that time. On repeat ultrasound examination he demonstrated dilatation of the right prevesical ureter. The cystography revealed presence of right sided VUR grade III. In conclusion: we present two siblings with VUR; although EYA1 gene mutation was found in one of them, it can not be incriminated for the renal phenotype in this family, as co-segregation of the mutation with the VUR does not occur in all affected members of the family. Decision to perform cystographic study should be still based on clinical grounds.

Associations Asymmetric dimethylarginine (ADMA) is a novel predictor of cardiovascular (CV) outcomes in adults. Aim: To evaluate ADMA in children with hypertension. Subjects: 23 children (4 girls/19 boys; median age: 15 yrs) with primary (n=10) and secondary (n=13) hypertension. Methods: ADMA levels were analyzed by ELISA method. In study subjects antropometrical data, ambulatory blood pressure monitoring (ABPM), left ventricular mass index (LVMI), carotid artery intimamedia thickness (cIMT), 24-hour urinary albumin excretion (UAE) and serum biochemical markers (lipids, uric acid) were also evaluated. Results: ADMA concentration was positively correlated to serum uric acid (r=0.42, p<0.05) and UAE (r=0.45, p<0.05). When analyzed in boys separately, more apparent correlation was found for UAE (r=0.57) and a tendency for ADMA to be associated with LVMI r=0.44, p=0.059). Interestingly, when analysis restricted to older children (above the median age), ADMA correlated to LVMI more significantly (r=0.65, p<0.05). No relation was found of ADMA to cIMT, lipids, and ABPM parameters. Moreover, patients with left ventricular hypertrophy (43%) and microalbuminuria (55%) had a tendency for higher ADMA values compared to those without these abnormalities (2.5±0.83 vs 1.74±1.1 μmol/l, p=0.081 and 2.39±1.23 vs 1.66±0.74 μmol/l, p=0.13, respectively). When data analyzed on the basis of ADMA values, patients in the top quartile showed the worst profile. When compared to the lowest quartile, they had higher LVMI (p<0.05), higher UAE (p<0.05; inter-quartile comparison p=0.012), and higher uric acid concentration (p=0.052). Conclusions: The associations of ADMA with known factors of CV damage found in this study provide evidence that ADMA is closely linked to the early CV dysfunction in hypertensive children. Nephrogenic diabetes insipidus (NDI) is a disease characterized by unresponsiveness of distal tubule and collecting duct to vasopressin. Although NDI usually presents with polydipsia and polyuria, most infants do not have any of these symptoms and presentation is with features of dehydration like fever, constipation, vomiting, failure to thrive and developmental delay. So, the diagnosis is usually delayed until hypernatremia is noted. Almost all infants go through a period of hypogammaglobulinemia at approximately the 5th-6th months of age. At this time, the serum Ig G level reaches its lowest point, and many normal infants begin to experience recurrent respiratory tract infections. The clinical findings of NDI and transient hypogammaglobulinemi of infancy (THI) may be seen at the same period. Here, we report a five-month old boy with NDI. On his history, he was admitted because of recurrent fever attacks and was diagnosed as THI when he was three-months-old. On his follow-up, hypernatremic dehydration was detected and he was diagnosed as NDI. At the time of diagnosis, he had intracranial calcification secondary to delayed diagnosis of NDI. In infants with NDI, recurrent fever attacks due to dehydration may occur and incorrectly lead to think as an infectious disease. We think that this report can be an important warning for clinicians. We analyzed NPHS1, NPHS2 and NEPH1 gene in 8 Japanese CNS patients independent of the patients in previous report (K.I. 2005) from different Japanese group which suggested that the mutation of NPHS1 was not a major cause of CNS in Japanese patients. We extracted genomic DNA from leukocytes and analyzed all exons and exon-intron boundaries for NPHS1, NPHS2 and NEPH1 using polymerase chain reaction and direct sequencing after informed consent had been obtained. The study was approved by the ethics committees of Okayama University medical school. Results: We found compound heterozygous mutations of NPHS1 in 4 patients and homozygous mutations in 2 patients. One of these 2 homozygous mutations was already reported in paper from Europe and was not found in more than 50 healthy Japanese. Another one cause defection of trafficking to the membrane as we reported before (K.I.2000 (K.I. , AJKD 2002 . The other 2 patients have only heterozygous mutation in NPHS1 that healthy parent also has. We could find any mutations in neither NPHS2 nor NEPH1 in the 2 patients with heterozygous mutation. One of these 2 patients has mild form of CNS. Another one has neither expression of Nephrin nor Podocin protein on kidney tissue by immunohistochemistry. Interestingly, 4 patients out of 8 have the same mutation in NPHS1 as nt2515(delC). Parents who have this mutation heterozygously were from neighboring prefectures. All mutations including this mutation but one have never been reported out of Japan which was isolated from continent. All amino acids substituted by missense mutations which seem to be causative were preserved among mouse, rat and human.

Conclusions: Our studies clearly demonstrated that NPHS1 is a major cause of CNS even in Japanese patients. Moreover, nt2515(delC) is a common mutation in Japanese CNS patients like Fin major or minor. Long-term survival of childhoodonset CKD is mainly limited by the manifestation of cardiovasculardisease (CVD). The development of early stages of CVD can be assessedby non invasive methods, e.g. flow mediated vasodilation (FMD) ofperipherial arteries and measurement of intima media thickness (IMT) of the common carotid artery. Wetherefore performed FMD and IMT investigations in 24 children and adolescents (mean age 15.8±5.1 years) suffering from CKD (mean GFR 44±33 ml/min/1.73 m 2 ) on conservative treatment (n=11), dialysis treatment (5 HD, 1 PD) and after renal transplantation (n=7), and in 24 sex-and age-matched healthy controls. CKDpatients showed significantly decreased FMD (5.2±3.1% vs 9.8±2.3%, p<0.001), where as IMT did not significantly differ between patients and controls (0.48±0.06mm vs 0.46±0.08 mm, p=0.13). Within the CKD group the presence of arterial hypertension tended to be associated with increased IMT (0.48±0.006 vs 0.45±0.05 mm, p=0.05). In contrast, duration of CKD, mode of renal replacement therapy and degreeof renal dysfunction was not significantly associated with FMD and IMT findings. Conclusion: Children and adolescents suffering from CKD show decreased arterial elasticity irrespective of the mode of renal replacement therapy, the rebycontributing to increased long-term cardiovascular morbidity and mortality.

The genetic researches have shown the connection between the essential hypertension and angiotensinogen gene. The researches of preeclampsia also showed the connection with angiotensinogen gene. According to established connection of angiotensinogen gene with essential hypertension and also preeclampsia the aim of our research was to determine by the help of M235T, G-6A andA-20C polymorphisms of angiotensinogen gene whether there is a genetic disposition for essential hypertension in those children whose mothers had preeclampsia. At the same time we wanted to establish whether the polymorphisms of angiotensinogen gene can be connected with preeclampsia in women in our population. Two groups of children were studied: children of mothers who had preeclampsia and children of mothers without hypertensive disease in the pregnancy. We also studied two groups of mothers: mothers who had preeclampsia and mothers without hypertensive disease in the pregnancy. M235T, G-6A and A-20C polymorphisms of angiotensinogen gene were performed using the PCR method. In investigating the differences between the two groups of children no statistically significant differences were found in M235T,G-6A and A-20C polymorphisms of angiotensinogen gene. In investigating the differences between two groups of mothers no statistically significant differences were found in genotype distribution. The results of our study failed to confirm that with help of M235T, G-6Aand A-20C polymorphisms of angiotensinogen gene we might establish genetic disposition for essential hypertension in those children whose mothers had preeclampsia. We did not confirm the association between M235T, G-6A and A-20C polymorphism of angiotensinogen gene and preeclampsia either. (11) previously treated also with cyclosporine. Before start of fosinopril treatment all had proteinuria 0.7-4.2 g/24 h and GFR >60 ml/1.73 m 2 /min. All active steroid and immunosuppressive treatment were discontinued. Eleven children also were treated with calcium channel blockers to control hypertension. After twelve months of fosinopril (0.3-0.4 mg/kg) treatment a DNA analysis for ACE-gene polymorphism was performed. Three patients carried II, 10-ID and 4-DD gene polymorphism of ACE gene. No significant differencein proteinuria at start of fosinopril treatment between all polymorphism types was observed. All 3 patients with II polymorphism had a good antiproteinuric effect of fosinopril with more than 4-fold decrease in proteinuria in comparison with just 2,3 fold decrease in ID polymorphism and no response in DD. Renal function remained stable in all children except of 2 with ID and 2 with DD gene polymorphism who demonstrated decrease in GFR. We suggest that II polymorphism of ACE gene may be associated with better antiproteinuric effect of ACEi while DD predicts poor response. Wider study is required to confirm genetic predisposition for ACE blockade efficacy in proteinuric diseases. Introduction: Dent disease is X-linked recessive proximal tubulopathy, due to mutations in the CLCN5 gene. It is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis and progresive renal failure. Aim: Case report of patient with short stature and proximal tubulopathy where Dent disease is determined by gene analysis.

Method: Seven-year-old boy is refered after endocrinological exemination where abdominal ultrasound showed nephrocalcinosis. There are anamnestic data neither of oedema, macrohaematuria, nor poliuria or hypertension. There are also no data of chronic renal failure in the family. We describe detailed diagnostic procedures performed in the boy and his family. Results: We determined: proteinuria (1,8 g/day), elevated urinary excretion of Beta-2microglobuline, microscopic hemathuria, hypercalciuria (8-10 mg/kg/day), nephrocalcinosis, decreased tubular reabsorption phosphate (65-72%). Values of grow hormone, parathormone on thyroid hormone are normal. Except hypercalciuria, which is registered in patient's mother, all other analysis performedin family members are betwen referent values. Diagnosis is finalized by mutation analysis, which has showed S244L substitution on CNCL5. Mutation carrier is mother with normal fenotype. Conclusion: Dent disease is rare X-linked nephrocalcinosis. Definitive diagnosis ofthis proximal tubulopathy which leads to progressive renal demage, is not possible without evidence of gene mutation in renal chlor channel. Introduction: The segmental renal infarction is a rare disease, allthough it is more frequent in children than in adults and can be clinically veryrelevant.

Objective: We describe the clinical course of two children with idiopaticsegmental renal infarction who suffered severe arterial hypertension. Cases description: The typical clinical picture of this disease, as seen in our twopatients, is characterized by metabolic alkalosis, hyponatremia, hypokaliemia, hyper-reninemia, hyperaldosteronism and renal salt lossfrom the contralateral enlarged kidney. Hypertension was diagnosedduring the study of haematuria in the first case and due to ahypertensive emergency in the second case. The ethiology was found tobe renovascular in both patients, involving the occlusion of small renal arteries causing segmental renal infarction. Our first patient was treated with partial nephrectomy, and the second patient wastreated with antihypertensive medication given the impossibility ofremoving the renal infarcted area. Conclusions: In the clinical picture, the sodium depletion with increased urinary volume of the contralateral healthy kidney can be explained by the Goldblatt model. The gold standard test for the diagnosis is theselective renal arteriography, which is the most sensible and specifictest for diagnosing renovascular hypertension secondary to a segmental renal infarction because it helps identifiing the segmentary artery ofthe infarcted area, this being the source of increased focal renin production. The definitive treatment is the surgical segmentectomy. If segmentectomy is not feasible because of the localization of the infracted area as inour second patient, a medical treatment is needed. Conclusion: Although an inverse association between birth weight/blood pressure has been suggested in several large studies, interpretation is still controversial. In our study, we have found only a weak inverse correlation between birth weight and PAD (ABPM): No statistical significance has been found among other variables, although graphs show a trend of low birth weight children towards hypertension. Probably a long term follow-up is necessary. He took longer to have improvement, but his calcemia, phosphatemia and alkalinephosphatase are normal. The coding region of the VDR was amplified by PCR and directly sequenced. Results: Three mutations (two novels) were identified. Two patients had anovel mutation in exon 7, changing the amino acid Glutamine to Glutamicacid at position 259 (Q259E). One patient had a novel mutation in exon 8 changing Glycine to Valine at position 319 (G319V). Those mutations are in the ligand binding domain and belong to the patients with better control of the disease. One had mutation in exon 3, in the DNA binding domain, changing Arginine to a stop codon at position 73 (R73X) and it was from the patient with worse response to the treatment.

Conclusions: two novel mutations are presented in the Vitamin D receptor and it could be possible to do a correlation between the clinical evolution and the localization of the mutations. We aimed to evalute the effects of intrauterine growth retardation (IUGR) on blood pressure (BP) in small for gestational age (SGA) children. 23 SGA children (6F,17M) aged 9.4±3.9 y (5 preterm and 18 term) and 13 (8F, 5M) agematched control with appropriate for GA (AGA) were included in the study. 24-hr ambulatory blood pressure monitoring (ABPM)was performed using an oscillometric device (MOBILOGRAPH). 95th centile limit was set according to published data sets, nocturnal threshold was 10% less than awake limits. BP was classified as normal if the mean SBP is <95th percentile and SBP load is >25%. Nocturnal BP dip for SBP and DBP were evaluated. In 2 SGA and in 1 AGA case, office SBP were above 95th%, all DBP values were normal in both groups. According to the mean of 52 ABPM records, 2 systolic,1 diastolic HT were determined in SGA group, and 3 systolic, no diastolic HT were in AGA group. There were 9 SGA and 5 AGA children whose SBP load over 25%, and only 5 of them remarked as hypertensive according to mean SBP values. 5 children considered as hypertensive had significantly higher SBP loads than those that were not hypertensive(38% vs 10%, p<0.05). ABPM records were not different between preterm and term SGAs. SGA group had lower nocturnal BPdip for SBP and DBP in comparison to AGA group(13.5% vs 14.5% for SBP,15.4%vs 18.1%for DBP, p: 0.62). Although it was not statistically significant, the frequency of non-dipper children was higher in SGA group (22.7%) than those in AGA group (8.3%). Except the lower nocturnal BP dip and higher SBP loads in SGA group which may be a marker for further hypertension, no clear association between being SGA and hypertension could be found in our study population. PRES is a rare clinico-radiological entity associated with acute hypertension, renal insufficiency and immunosuppressive therapy. It is typically reversible but cases with irreversibility had rarely been reported. We report 2 contrasting cases of PRES associated with renal disease, one with full recovery and the other subsequently had epilepsy. First patient had steroid sensitive nephrotic syndrome with acute hypertension, fluid overload and acute renal failure while the second patient had severe flare of lupus nephritis with malignant hypertension, renal failure and thrombotic thrombocytopenia. Both had acute onset of drowsiness, blindness and seizures and MRI findings of subcortical oedema in the parietal-occipital-temporal regions. While the second patient had full recovery, the first patient developed temporal epilepsy and repeat MRI showed mesial temporal sclerosis. PRES is attributed to capillary leak from functional cerebral vascular changes of hypertension, rather than infarction. Prolonged vascular disruption may lead to ischemia resulting in neurological sequelae and chronic epilepsy. Using MRI, PRES can be readily diagnosed and normalisation of blood pressure is imperative in patients at high risk of PRES. Efforts have been done to describe the significance of various genetic polymorphisms (SNPs) in acute renal failure (ARF). Available reports do not investigate the predictive value of SNPs in disease forecasting, because so many interacting factors influence ARF that classical statistical methods become unstable. High-dimensional nonparametric methods such as random forest technique overcome this problem and help to identify each clinical and genetic factor that possibly contributes to disease. We tested the classification value of basic clinical data available at birth and 19 SNPs in ARF of 111 preterm infants. We determined the relative importance score (RI) of each parameter in classification. Low birth weight and gestational age had the highest RI; just few SNPs had medium RI, while the majority of SNPs had small RI. Then we created variable-patterns and searched for pattern with the highest accuracy of classification. For each complication, the accuracy was 0.71 solely basic clinical data were considered. If SNPs were incorporated, the accuracy of classification for ARF was not improved. In contrast with previous observations these findings suggest that the SNPs do not provide additional information about ARF-risk of the general preterm population. Conclusions: SRBD in children with elevated blood pressure is higher than that of the general pediatric population. The prevalence appears highest in patients with pre-hypertension and may be higher in patients with essential and secondary hypertension than in patients with white-coat hypertension.

The Renal Phenotype in Lowe Syndrome is Similar to Dent's Disease 

A 22-month-old girl presented with heart failure due to severe hypertension (200/120). Doppler ultrasonography (US) revealed a right renal artery stenosis. Biological findings showed normal serum creatinine (sCr) (35 mmol/l), hyponatremia (131 mmol/l) and hypokalemia (3 mmol/l). Aldosterone plasma level was increased as were epinephrine (429 pg/ml N<185) and norepinephrine (1230 pg/ml N<450) plasma levels measured 3 times. Renal arteriography confirmed the presence of a nearly obstructive right renal artery stenosis with a normal left kidney. PTA failed to improve signifcantly the renal artery flow. In the following hours after PTA, her sCr level increased, up to 160 mmol/l. Doppler US showed an unchanged right kidney but 3 hypoperfused area in the left kidney confirmed by the Tc 99 -DMSA scan. Both aspects were strongly in favor of focal ischemic events. Secondarly, her renal function improved but hypertension remained difficult to control Autotransplantation of the right kidney was then done, but unfortunately, thrombosis of the right renal artery occured in the following hours. Six months later, her plasma creatinine level is of 55 mmol/l. Her cardiac function is normal but she has to remain on antihypertensive drugs. What exactly happened during arteriography in her left kidney, in order to provoke such ischemic injury, knowing that the left renal artery was not catheterized during arteriography and PTA? One hypothesis is that arterial vasospasms occured, explained by a high vasospastic predisposition due to enhaced cathecolamines secretion. Such increased has already been drescribed in patients with renal artery stenosis. This case raised the question of preparing patients in this condition with efficient antispasm therapy agents before radiological vascular investigations are done. RTD is a cause of oligohydramnios leading to Potter's sequence and neonatal anuria. It is characterized by absent or hypoplasic proximal tubules. These lesions can be secondary to non genetic conditions involving renal hypoperfusion. Genetic forms of RTD have autosomal recessive transmission. Mutations of genes encoding for the renin-angiotensin system have been reported. Evolution is most often severe with in utero or neonatal death. Case report: This boy was born at 38 weeks of gestation with oligohydramnios, arthrogryposis, large fontanels with poor calvarian ossification. He was referred to intensive care unit for respiratory distress, low blood pressure (BP) unresponsive to vasopressors and anuria (plasma creatinine 370 μmol/l at day 3). Renal ultrasound (US) showed enlarged kidneys with bilateral cortical hyperechogenicity. Weaning from ventilation and vasoactive drugs was possible at day 7. Glomerular filtration recovered (plasma creatinine 45 μmol/l at day 26). At age 10, the child is well with normal growth and a mild chronic renal insufficiency (creatinine clearance 75 ml/min/1,73 m 2 ). BP is in the low normal ranges with plasma renin x40 over the upper range of normal values and normal plasma aldosterone. On renal US, kidney volume normalized with persistent cortical hyperechogenicity.

Genetic study revealed compound heterozygous mutation in the gene encoding angiotensin converting enzyme. One is a nonsense mutation (R1209P), the other is a truncating mutation (K601fsX640). It is possible that the first mutation is less deleterious than the other and this could partly explain the unusually favourable evolution of this RTD.

In conclusion, this is a rare report of a child with autosomal recessive RTD surviving after neonatal period. Further functional studies are needed to explain this unusual phenotype. Data on HBP in children are very limited, and it is unclear how much it is specific in pediatric patients. The objective of our study was to determine the reproducibility of HBP in children and adolescents. Automatic OMRON 705-CP devices, which have been validated for use in children and adolescents, were provided to all families. Hypertensive children measured blood pressure (BP) every minutes, three times consecutively in the morning or early afternoon, and three times in the evening during 13 days. The reproducibility of HBP was quantified using repeated measures analysis of variance test and the SD of differences between average HBP values of consecutive days. Confidence interval (CI) was calculated. We studied 41 patients (14 girls, 27 boys); mean age was 12,1 year, range 4-18 years. There were 78 measurements of systolic blood pressure (SBP) and diastolic blood pressure (DBP). In the morning or early afternoon the mean SBP and DBP were 110,9 mmHg (SD 10, 65) (95% CI 107, 5-114, 3 mmHg) and 64, 4 mmHg (SD 9, 08) (95% CI 61, 4-67, 3 mmHg), respectively. In the evening the mean SBP and DBP was 111,6 mmHg (SD 10,14) (95% CI 108,3-114,8 mmHg) and 65,0 mmHg (SD 8,83) (95% CI 62,2-67,9 mmHg). The mean average difference between the daily measurements of SBP and DBP were analyzed with each period and were not statistically significant (p>0.05). On the basis of these results, we conclude that self-monitoring of blood pressure at home in children has good reproducibility and is not influenced by white coat effect. Case Report: A 3-year-old Caucasian girl presented with history of severe polyuria and polydipsia of few months duration. Past history was significant for head injury and possible seizure activity at age 1 yr. There was no history of headaches, vomiting, or visual problems. Family history negative for DI. Physical examination was essentially normal. Basal plasma and urine osmolality, and plasma vasopressin were 294 and 96 mOsm/kg, and <0.5 pg/ml, respectively. At the conclusion of water deprivation test these readings were 309 and 98 mOsm/kg, and 31.3 pg/ml, respectively. However, urine osmolality increased to 493 mOsm/kg after desmopressin injection, confirming the diagnosis of CDI. MRI scan revealed absence of the bright spot on T 1 weighted images. Genetic analysis detected AVP gene mutation A19T, where the normal alanine at amino acid position 19 is changed to threonine. Elevated levels of plasma vasopressin after water deprivation were misleading and intriguing. We believe that elevated plasma vasopressin, although immunoreactive was devoid of biological activity.

Conclusion: Molecular genetic evaluation should be performed in all children with CDI without an identifiable cause, even in the absence of a positive family history of CDI. Mutations of the NPHS2 gene encoding podocin lead to autosomal recessive corticoresistant nephrotic syndrome, focal and segmental glomerulosclerosis (FSGS), and early end-stage renal disease (ESRD). In mice, podocin inactivation by homologous recombination results in diffuse mesangial and glomerular sclerosis, ESRD and death within the first 5 weeks of life. This early demise precludes extensive study and elucidation of the molecular pathways engaged by podocin in the mature kidney. We have, therefore, generated a novel mouse model in which a tamoxifeninducible CreER-loxP system allows for conditional inactivation in a temporal fashion in podocytes. Following tamoxifen administration in Nphs2 flox/-, Cre+ mice, Cre expression was noted in 88% of glomeruli and in 60-70% of podocytes. Two weeks after Cre induction, podocin expression is decreased in podocytes correlating with the appearance of selective albuminuria at 10-16 days. This progresses to massive, nonselective proteinuria by 4 weeks, along with high blood pressure and impaired renal function. Optical microscopy of kidneys showed no lesion at 1 week and FSGS progressively developed by 4 weeks along with tubular lesions. However electron microscopy revealed a partial foot process effacement at 1 week with no significant albuminuria that extends by 2 weeks along with abnormalities of the basement membrane and development of albuminuria. No mesangial or vascular lesion has been noted, differentiating it from our previous podocin null model in which renal development may be affected by podocin loss or nephrotic syndrome. This model will allow a better understanding of the mechanisms underlying the development of nephrotic syndrome and the role of podocin in the mature kidney, and will be crucial to test new therapeutic approaches.

Glomerulonephritis is a group of diseases with complex etiology, pathogenesis, morphological features and clinical course. The renin-angiotensin and coagulation systems genes are important group of candidate genes involved in pathogenesis of chronic renal diseases. The purpose of our study was to analyze the association of genetic polymorphisms of these genes with glomerular kidney diseases. The study population consisted of 181 patients with immunological glomerular kidney diseases and 19 patients with renal failure with glomerulonephritis as primary disease. The control group consisted of 80 healthy subjects. By means of the polymerase chain reaction (PCR) the following polymorphisms were evaluated: insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin-converting enzyme gene (ACE), 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1). No significant association was found between the ACE and PAI-1 allele and genotype frequencies and the disease. More progressing of glomerulonephritis current was marked at patients with simultaneous has DD genotype of ACE gene and 4G/4G gene PAI-1(c 2 =9,1; p=0,008). Our results suggest that ACE I/D and PAI-1 4G/5G polymorphism is an important modifying gene in the progression of glomerulonephritis.

Captopril Objectives: Secondary causes of hypertension such as renovascular hypertension are more abundant in children unlike adult population. The objective of this retrospective study is to assess the use of captopril renography (CR), which provides a non-invasive approach in the differential diagnosis of hypertension.

Patients and methods: Clinical, radiological and scintigraphic data of a total of 64 patients were analyzed. There were 22 girls and 42 boys (mean age: 13±3 years). None of the patients had parenchymal renal disease or reduced renal function. All patients were orally hydrated before scintigraphic study. CR was performed 1 hour after orally captopril administration and iv furosemide injection was done simultaneously with 1-5 mCi Tc99m-MAG3. When post-captopril study was normal, baseline scintigraphy was not performed. Computed tomography angiography (CTA) was performed in 11 and gadolinium-enhanced magnetic resonance angiography (MRA) was performed in 8 children in addition to routine renal Doppler ultrasonography (DUS).

Results: Nineteen out of 64 patients had other comorbid diseases as follows: obesity n=10, previosly-diagnosed fibomuscular dysplasia n=3, n=2 neurofibromatosis, n=2 demyelinating diseases, n=1 Bartter and n=1 Turner Syndrome. CR was normal in 48 patients. In 8 children abnormal CR findings in correlation with radiological methods were reported. Correlation with radiological methods could not be done due to suboptimal technique in 7 patients, of whom DUS in 5 obese children could not be interpreted. In the other 1 patient, although CR was abnormal, radiological methods could not confirm scintigraphy. Conclusions: Captopril renography is a useful and simple-to-perform imaging modality in children suspected of having renovascular hypertension. Takayasu's arteritis (TA) is a chronic, inflammatory, large-vessel vasculitis affecting the aorta and its main branches, which causes stenosis, occlusion, rarely aneurysm and distal ischemia. The disease is most common in young women, it is rare in inviduals before the age of 16 years. Clinical presentation may be heterogeneous. In this report, we present a pediatric patient with TA who had hypertension as the sole manifestation of multipl critical arterial involvement but no other symptoms. A 14-year-old boy was admitted with hypertension. The acute-phase reactants were moderately elevated with an erythrocyte sedimentation rate 70 mm/h, and a C-reactive protein value of 26 mg/L. Serologic tests including ANA, Anti-ds DNA, c and pANCA, complement C 3 , and C 4 were negative and other laboratory data were normal. MR angiography showed multiple severe stenosis or occlusions of the thoracic and abdominal aorta together with bilateral renal arteries, and saccular aneurysm in the abdominal aorta. Immunosuppressive treatment including pulse steroid and methotrexate was prescribed. The patient underwent angioplasty of bilateral renal arteries and suprarenal aorta, and a stent was placed in the right renal artery. TA should be kept in mind in the differential diagnosis of hypertension in children, even if they do not have other associated symptoms of the disease. Human urotensin II is the most potent vasoconstrictor which circulates in the plasma of healthy individuals. It was suggested that it has an endocrine role in sodium handling and even in metabolic syndrome. The aim of this study was to investigate the role of U-II in obese adolescents with hypertension. Fourteen obese adolescents with essential hypertension (group 1) were compared with thirteen age-and sex-matched obese adolescents with white-coat hypertension (group 2). They underwent twenty-four hour ABPM and echocardiographic investigation, complete physical examination, including adiposity indexes. Plasma and urinary levels of U-II were measured by RIA. Obese adolescents in group 1 have significantly higher blood pressure measurements than those in group 2 confirmed by ABPM. There was no significant difference in left ventricular mass index between two groups. No significant difference was found in plasma U-II concentrations (pg/ml) between group 1 and group 2 (35.23±4.90 and 35.98±5.74, respectively), whereas mean urinary U-II level (pg/mg urinary creatinine) was significantly higher in group 2 than that of group 1 (28.80±6.83, 44.44±16.78, respectively). Considering the renal synthesis and vasoactive role of U-II, these results suggest that U-II may have a role in adolescents with white-coat hypertension. Distal renal tubular acidosis (dRTA) and deafness is a rare autosomal recessive disease characterized by severe metabolic acidosis in childhood and inappropriately high urinary pH along with sensorineural hearing loss. The disease is caused by defects in the ATP6V1B1 gene. The aim of the present study was to determine the molecular basis for dRTA with deafness in eight patients from four families (A-D) in Israel. Molecular testing was done by sequencing the coding exons of the ATP6V1B1 gene in one affected child from each family. A population screen was performed for mutations found in family A. The results yielded a different mutation in the ATP6V1B1 gene, as follows: Families A and D: missense mutation, 1037C>G (P346R), in addition to a single nucleotide polymorphism (2T>C) in the first codon; Family B: insertion mutation, 1155-1156insC (I386fs); Family C: a novel nonsense mutation, 340 C>T (R114X). In conclusion, the phenotype of dRTA and deafness concurs with mutations in the ATP6V1B1 gene. In the present study, four families of different origins with the same phenotype had three different genotypes, indicating that there is no single common mutation in Israel. These findings have implications for genetic counseling during pregnancy and testing of families. The fact that all the patients that were examined have harbor mutations in the ATP6V1B1 gene, pointed for the specific clinical phenotype. Making correct and early clinical diagnosis is a fundamental step in finding the molecular basis of this rare disorder. Delta F508 is the most common cystic fibrosis (CF) mutation worldwide. The prevalence is approximately 70% in Caucasian and 14-55% in Asian while F311L is demonstrated in only 0.2%. Homogenous Delta F508 mutation is recognized as the most common genotype however there are small numbers of CF patients having Delta F508/F311L. In the present study we report a 2 year-old Thai boy, originated from North India, presented with recurrent episodes of febrile illness, hyponatremia, hypokalemia and metabolic alkalosis since 4 months of age. He was transferred to our hospital for further investigation. Blood chemistry revealed serum electrolytes: sodium 122, potassium 3.69, chloride 79.7, bicarbonate 33.8 mEq/L, and urine electrolytes: sodium<10, potassium 45.7, chloride<10 mEq/L. After intravenous fluid administration, hyponatremia and metabolic alkalosis improved. DNA sequencing analysis of his blood demonstrates compound heterogenous mutation for Delta F508 and F311L in CFTR gene. T to G transversion at nucleotide 2694 and G to A transversion at nucleotide 4521 are found without altering amino acid encoding gene. In conclusion, we report a rare case of CF with Delta F508/F311L genotype presented with recurrent hyponatremia and metabolic alkalosis. Awareness of electrolyte abnormalities during febrile illness, proper genetic counseling and long-term follow-up are necessary in this patient. Objectives of Study: About 10% of families with congenital nephrogenic diabetes insipidus (NDI) have mutations in the aquaporin 2 gene (AQP2), which codes for the vasopressin-sensitive water channel. Only seven AQP2 mutations are known to cause a dominant form of the disease. In this study we performed genetic and clinical studies in a 5 generation family with autosomal dominant inheritance of a partial DI phenotype. Methods and Results: The proband (man, 37 yrs old) was initially diagnosed with partial central diabetes insipidus due to antidiuretic effect of dDAVP. His daughter (1.3 yrs old) also showed polyuria and polydipsia which was responsive to high doses of intranasal dDAVP. The pedigree was consistent with an autosomal dominant inheritance pattern. Sequence analysis of the entire coding region of the AVP gene and AQP2 gene was performed in the proband and his affected daughter and in 2 unaffected family members. The AVP gene was normal in all subjects. In the two affected patients but not in the healthy subjects we identified a novel missense mutation in one allele of exon 4 of the AQP2 gene (c.760C>T) which predicts a substitution in the C-terminal part of the AQP2 protein (p.R254W). Conclusion: Partial NDI can be caused by heterozygosity for a p.R254W substitution of the AQP2 water channel. The substitution is likely to significantly alter the C-terminal tail of aquaporin 2 which is important for proper trafficking to the apical plasma membrane. The preservation of some residual antidiuretic function indicates that some AQP2 tetramers are processed correctly. The study further illustrates the importance of molecular diagnostic tools in establishing a correct differential diagnosis in familial cases of DI.

A Background and Aim: Dent's disease is a renal tubulopathy characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis and nephrolithiasis. Mutations in the CLCN5 gene encoding the chloride/proton exchange transporter ClC-5 cause this disease. We have described an Alu insertion in CLCN5 that leads to exon 11 skipping in the patient's mRNA. In this study, we investigated the consequence of this mutation on the function of two putative exonic splicing enhancers (ESEs) in exon 11 and the role of Alu 5'-end sequences on splicing inhibition. Methods: Minigenes were constructed by inserting exon 11 and exon 11-Alu with their intronic flanking sequences into the Exon Trap vector. Artificial mutations were introduced by site-directed mutagenesis. Plasmids were transfected into COS7 cells by electroporation. Pre-mRNA splicing analysis was performed by RT-PCR. The ESE Finder Web resource was used to predict the mutagenesis effects on the ESEs. Results: Alteration of one of the putative ESEs, the predicted binding site for SRp40, induced exon 11 skipping. Restoration of this site within the Alu sequence promoted the incorporation of exon 11-Alu in the mRNA. However, restoration of both ESEs leaving the Alu sequence intact resulted in exon skipping. Furthermore, substitution of the ESEs for the first seven nucleotides of the Alu element, and insertion of this sequence next to the ESEs increased exon skipping. Deletion or modification of the Alu 5'-end enhanced exon 11 inclusion in the mRNA.

In the patient carrying the CLCN5 Alu insertion, Dent's diseases is caused by disruption of an ESE and by inclusion of splicing inhibitory sequences leading to exon skipping. This work was supported by grant PI042620 from Fondo de Investigación Sanitaria. Factor H-associated Hemolytic Uremic Syndrome (FHD-HUS) is a rare disease with incomplete penetrance. It is not clear why and how carriers of the same mutation will eventually develop or not develop the disease and this uncertainty is sometimes responsible for anxiety in the carriers badly affecting their quality of life (particularly of parents with children carrying the mutation).

In the attempt of estimating disease risk in subjects with factor H gene mutation, the 6 families of FHD-HUS patients (all of which had a documented mutation on the SCR20) currently being treated at our Center, were screened to identify the carriers after having been informed on the purpose of the analysis. Twenty-eight subjects (age range 0-89 yrs), out of 55 analyzed, revealed heterozygous mutations in the carboxy-terminal region of FH1 gene (51%). Among subjects carrying the mutation, 9 (32%) had exhibited the disease at a mean age of 12 years (range 0.2-32), 6 of which (67%) before age 10, whereas the remaining 19 subjects (mean age of 53 yr -range 11-89) were healthy at time of the study. The figure shows the probability of carriers to be HUS-free by age (no event occurred after age 32 yrs). In the meantime that predisposing factor are identified, the presented survival curve (Fig.1) can be an useful tool to estimate the residual risk of HUS in individual carriers according to their specific age. Cerebello-oculo-renal syndrome (COrS) (also called Joubert syndrome (JS) type B) and Meckel (MKS) syndrome belong to the cilliopathy group of developmental autosomal recessive disorders associated with primary cilium dysfunction. Nephronophthisis (NPHP), the most frequent genetic cause of renal failure in children and young adults, is associated with retinal degeneration and cerebellar vermis aplasia in CORS. MKS is characterizd by renal cystic dysplasia, central nervous system malformations and hepatic developmental defects. These syndromes are genetically heterogenous: mutations in AHI1 and NPHP1 can cause COrS and mutations in MKS1 can lead to MKS, while mutations in MKS3 and NPHP6 are found in both syndromes. Using SNP mapping, we identified missense and truncating mutations in a novel genee, nPHP8, in both CORS and MKS. Interestingly, all sequence changes were either nonsense or frameshift mutations in fetuses with MKS whereas patients with CORS had either only one or no truncating mutation. We then show that inactivation of NPHP8 mouse orthologue recapitulates the cerebral and renal defects of CORS/MKS. We further demonstrate that NPHP8 protein co-localizes at the basal body/centrosomes with nephrocystin-6 and nephrocystin-4, the protein products of both NPHP6 and NPHP4, known disease genes for NPHP. In addition, missense mutations of NPHP8 protein found in CORS patients diminishes its interaction with nephrocystin-4. Taken together. our findings demonstrate that mutations of this novel ciliary gene can cause the multiorgan syndromes of either CORS or MKS, which therefore represent a continuum of the same underlying disorder.

Severe Antenatal Bartter's Syndrome GA 25 + 4, BW: 750 g). Both had classical signs of antenatal BS including very poor thrive, polyuria (5-10 ml/kg b.w./h) and responded to indomethacin treatment. Direct sequencing was performed on PCR-amplified genomic DNA. The entire coding region of both genes was analyzed. The KCNJ1 gene was normal but both children were homozygous for a single base substitution (39671T>A) in exon 12 of the SLC12A1 gene predicting a premature stop codon (Y538X). The parents of both children and two siblings were heterozygous for the same mutation. By restriction enzyme analysis, the 39671T>A substitution was absent among 100 chromosomes from healthy subjects. Conclusion: Two children with severe antenatal BS were identified and the clinical phenotype was characterized. We identified in both children a novel mutation causing a premature stop codon of the bumetanide-sensitive-sodium-potassium-chloride co-transporter (NKCC2). Despite large potassium supplements and indomethacin treatment, both children show persistent polyuria, vomiting, and insufficient thrive.

Background: Mutations of NPHS1 encoding the transmembrane slit diaphragm protein nephrin cause congenital nephrotic syndrome of the Finnish type, characterized by massive proteinuria and the development of nephrotic syndrome before 3 months of age. About 70 different NPHS1 mutations have been described. A large number of these are missense mutations resulting in single amino acid replacement mostly located in the extracellular domain. Some NPHS1 mutations have been associated with mild phenotypes responding to angiotensin-converting enzyme and prostaglandin synthesis inhibition. Patient history: We report on a son of consanguineous turkish parents with a novel NPHS1 alteration and steroid-resistant congenital nephrotic syndrome. After normal pregnancy and delivery at 37 weeks of gestational age the boy presented with edema and proteinuria at the age of 2 months. He responded to Angiotensin Converting Enzyme inhibitor treatment reducing his proteinuria from a maximum of 66 g/g creatinine to 10 g/g creatinine and allowing him to develop normally until the age of 7 months when cardiovascular insufficiency in the course of a hyperpyretic infection led to hypoxic encephalopathy. Genetic testing revealed a homozygous in-frame 3-bp insertion in exon 11 of NPHS1. Both parents were found to be heterozygous. No mutations were found in NPHS2 or in exons 8 and 9 of WT1. The alteration results in an insertion of a glycine in an extracellular immunoglobulin domain of nephrin. The pathogenicity of this alteration is unclear. Nephrin may be misfolded and mislocalized as in some missense mutations of the extracellular domain. Alternatively the alteration might lead to an altered extracellular homo-and heterodimerization of nephrin. Functional studies are currently underway to determine the effect of this novel alteration in NPHS1. Objectives of Study: Interleukin 1 receptor antagonist (IL-1Ra) gene polymorphism has been found to affect disease susceptibility and activity in several inflammatory diseases. We investigated the association between IL1Ra gene polymorphism and childhood nephrotic syndrome (NS) in a Turkish population. Methods: We analyzed the genetic polymorphism of IL-1Ra gene in 91 patients with childhood NS and 100 healthy controls by using PCR. Five alleles of the IL-1Ra gene were identified and designated as IL-1Ra*1, IL-1Ra*2, IL-1Ra*3, IL-1Ra*4, and IL-1Ra*5, according to the variable number of tandem repeats in intron 2.

Results: In the NS group, the allele frequencies of IL-1Ra*1, IL-1Ra*2, IL-1Ra*3, IL-1Ra*4, and IL-1Ra*5 were 74.7, 13. 2, 4.4, 2.2, and 5 .5% compared with 58%, 28%, 1%, 0%, and 12% in the controls. A high allele frequency of IL-1Ra*1(x 2 =5.28, P=0.021) and a lower allele frequency of IL-1Ra*2 (x 2 =6.31, P=0.012) were found in childhood NS. The other polymorphisms were not significantly different from normal controls.

Conclusions: A high allele frequency of the IL-1Ra*1 allele may affect the disease susceptibility in childhood NS. Objectives of study: Congenital anomalies of the urinary tract (CAUT) are common in humans, and the incidence is increasing with recent advances in prenatal ultrasonographic examinations. Interstitial fibrosis, which correlates with infiltration of inflammatory cells is common finding in the kidney with long-term ureteral obstruction. Up-regulation of monocyte chemoattractant protein-1 (MCP-1), may be a common regulatory pathway involved in the progressive renal damage with any etiologies leading to interstitial fibrosis. MCP-1 gene polymorphism -2518 A/G had been suggested to influence circulating MCP-1 levels and gene expression thus, might be one of the genetic markers for progression of renal damage. Our aim was to investigate the frequency of MCP-1 genotypes and allele -2518G in patients with CAUT. Objectives of study: Congenital urological anomalies are well recognized as causing renal dysfunction. On the other hand, patients without congenital anomalies but with urinary bladder dysfunction (BD) could also develop renal parenchymal damage. It has been reported that angiotensin converting enzyme (ACE) I/D polymorphism was a risk factor for renal parenchymal damage in certain renal diseases including vesicoureteral reflux. The aim was to determine I/D polymorphism as a potential risk factor for renal parenchymal damage in patients with congenital obstructive uropathy and to compare them to patients born with normal anatomy and innervation of bladder, sphincter and pelvic floor but which could develop upper urinary tract abnormalities. Objectives od study: To determine the frequency of pyelocaliceal dilation (PCD) in asymptomatic infants and its connection with presence of other urinary tract anomalies (UTA) and urinary tract infection (UTI). Methods: Ultrasonographic screening (US) of urinary tract (UT) was performed on unselected population of 1000 healthy infants ranging between 7 days and 6 months of age (511 boys and 489 girls). Kidneys were divided into two groups according to grade of PCD. Group I consisted of kidneys with PCD, whose anterio-posterior diameter was 5-10 mm, while patients from the group II had A-P diameter wider than 10 mm.Patients were followed up (ranging 5-58 months) by serial ultrasound examinations and with other methods for presence of UTI and UTA if necessary. Results: In examined population 2,2% had UTA, and 8,4% had UTI. PCD was found in 74 infants (7,4%). In the group I, consisted of 63 infants (35 males and 28 females) PCD increased during the time in 3,2% infants, remained unchanged in 11,1%, decreased in 14,3%, and disappeared in 71,4% patients. UTA was found in 4 (6,3%) infants, and UTI in 9 (14,3%) infants. In the group II, consisted of 11 male infants, PCD has not changed in 5 (45,4%) infants, decreased in 2 (18,2%), while dilation disappeared in 4 (36,4%) patients. UTA was found in 6 (54,5%), and UTI in 4 (36,4%) infants.

Conclusions: US of UT is useful and valuable method for detecting PCD. Our results indicate that mild PCD in infants increases the risk for UTA approximately 3 times and UTI 2 times, while severe PCD raises the risk for UTA approximately 24 times, and UTI 4 times. Early diagnosis and early treatment of UTA and alertness for possible UTI should be the final goal of the kidney damage prevention. Therefore we recommend that US of UT should be done in all children in the first months of life. In order to determine factors involved in kidney development, the spatial and temporal expression pattern of intermediate filaments (cytokeratins, vimentin) , epithelial growth factor (EGF) and transforming growth factor alpha (TGF-α), was investigated in developing kidneys (mesonephros and metanephros) of 5-9 week human embryos. Immunohistochemistry for detecting specific antibodies was used on paraffin sections. In the 5-9 week human mesonephros, vimentin was moderately expressed in all mesonephric structures, while cytokeratins were seen only in the mesonephric nephrons. Moderate to strong expression to EGF and TGF-α detected in all mesonephric structures, decreased with advancing development. In the 5-6-week metanephros, vimentin was mildly expressed in all metanephric structures. Later on, its expression increased in collectin system and interstitium. In the 5 th developmental week, first to appear were cytokeratins 8 and 19 in the ureteric bud and ampullae, while from the 8 th week onward, both cytokeratins showed increasing expression in the collecting system and nehrons. At early stages, EGF and TGFá showed moderate to strong reactivity in the collecting system, the metanephric mesenchyme and cups. From the 7 th week onward, expression of both factors decreased in differentiating nephrons. Expression of all investigated developmental factors was in line with subsequent mesonephric degeneration. Expression pattern of intermediate filaments in the metanephros might be associated with mesenchimal to epithelial transformation of developing nephrons. some mutations of cytokeratins are lethal, while others might lead to some multifactorial disorders. EGF and TGF-α expression patterns of the metanephros indicate their role in induction, proliferation and growth of metanephric structures. Their disturbed expression might cause reduction in kidney growth. We have demonstrated that renin-angiotensin system (RAS) and mitogen-activated protein kinase (MAPK) family constribute to the renal development. Growing evidences indicate that aldosterone, a final element or RAS, is an independent and powerful mediator of various renal disease. Purpose of this study was to evaluate the role of endogenous aldosterone in renal development including cell proliferation and apoptosis, and the expression of MAPK family. Newborn rat pups were treated with spironolactone (200 mg/kg/d) in olive oil or vehicle for 7 d. To identify cellular changes, kidneys were examined for proliferating cell nuclear antigen (PCNA) by immunohistochemical (IHC) stain, and apoptotic cells by TUNEL stain. Immunoblot, IHC stain and RT-PCR for MAPKs, phospho-MAPKs, and p53 gene were performed. Spironolactone treatment resulted in decreased body weight, decreased PCNA-positive proliferating cells and increased TUNEL-positive apoptotic cells, especially renal cortical epithelial cells (p<0.05). In the spironolactone-treated group, c-jun N terminal kinase (JNK)-2 and phospho-JNK-2 protein expressions were significantly increased, whereas extracellular signal -regulated kinase (ERK)-2 and p38 protein expressions were sigificantly decreased compared with the control group (p<0.05) in immunoblot and IHC stain. Expressions of ERK-1, phospho-ERK-1 and 2, and p53 sere not changed by spironolactone treatment. In RT-PCR, ERK-2 and p38 mRNA expressions were significantly increased in the spironolactone-treated group (p<0.05). We conclude that aldosterone inhibition in the developing rat kidney decreases cellular proliferation and increases apoptosis, and modulates the expressions of JNK-2, ERK-2 and p38. MAPK family expression may be implicated to differentially participate in aldosterone-related intracellular signaling pathways in the developing kidney. Objectives: Early detection of anomalies of the kidney and urinary tract (UT) helps to prevent complications but is hampered in Moldova by diagnostic and logistic problems. To assess the extent of late diagnosis we studied the clinical data of all children referred to us for suspected UT infection (UTI) in 2004/5 and found to have renal or UT anomalies. Methods: 92 children (27 males; age 3 months-15 years) found to have anomalies of the kidney and UT and treated conservatively were studied (newborns and infants <3 months were seen elsewhere). Work-up included ultrasonography in all, voiding cysto-urethrography (VCUG) in 40%, urography in 57% and scintigraphy in 3% of patients. Results: Reasons for referral were febrile UTI (38%); abdominal pain (31%), diarrhea and vomiting (16%), enuresis (9%) and dysuria (6%). UTI was confirmed by urine culture in two thirds of cases. Age at diagnosis of renal or UT anomaly was <1 year in 9%, 1-3 years in 6%, 3-7 years in 7%, 7-10 years in 30% and >10 years in 48%. Renal hypo/dysplasia was found in 14, solitary kidney in 10 and a horseshoe kidney in 9 children. Anomalies of the UT included hydronephrosis due to ureteral obstruction (13 UP and 11 UV-obstruction), vesico-ureteral reflux (8), duplex systems (17) and bladder anomalies or mild infravesical obstruction (10). Serum creatinine was in the normal range in all children. Urolithiasis was found in 2 patients. Conclusions: Anomalies of the kidney and UT were diagnosed in nearly half beyond the age of 10 years, thus with considerably delay. Based on the results of this study a new strategy of renal ultrasound screening in newborns including prenatal diagnosis and of closer co-operation with referring physicians has been implemented. Objective of the study: The purpose of this study was to report the outcome of infants with antenatal hydronephrosis.

Methods: Between May 1999 and June 2006, all patients diagnosed with isolated fetal renal pelvic dilatation (RPD) were prospectively followed at asingle tertiary Renal Unit. Inclusion criteria were presence of RPD equal to or greater than 5 mm on prenatal ultrasound after 28 weeks gestation, at least six-months of follow-up, and at least two postnatalUS scans. The events of interest were presence of uropathy, RPD resolution, urinary tract infection (UTI), and hypertension. RPD was classified as mild (5-9.9 mm), moderate (10-14.9 mm) and severe (>15 mm Objective of the study: The aim of this study was to compare the accuracy of ultrasound renal parameters to discriminate between significant uropathy and idiopathic renal pelvis dilatation. Methods: 193 neonates who were found to have isolated fetal renal pelvis dilatation (RPD) underwent systematic investigation and were prospectively followed. A US scan was performed after the first week of life and all infants underwent VCUG. Neonates with RPD larger than 10 mm were examined by renal scintigraphy. Receiver-operating characteristic (ROC) plots were constructed to determine the accuracy of three indexes: fetal RPD, postnatal RPD, and SFU grading system. Results: A total of 193 infants were included in the analysis. Ninety-five fetuses (49%) presented bilateral renal pelvis dilatation. Seventy-nine infants (41%) presented urinary tract anomaly, corresponding to 95 renal units. The most frequent detected uropathy was ureteropelvic junction obstruction (61), followed by primary vesicoureteral reflux (26), and megaureter (8) Conclusions: Our data support the view that fetal and postnatal US renal parameters are useful markers to identify infants with clinically significant uropathies. There was no significant difference in performance among the indexes. Objective of the study: The aim of this study was to evaluate the diagnostic accuracy of ultrasound (US) renal parameters to identify VUR in infants withisolated antenatal hydronephrosis. Methods: 193 neonates who were found to have isolated fetal renalpelvis dilatation (RPD) underwent systematic investigation and wereprospectively followed. A US scan was performed after the first week of life and all infants underwent VCUG. Neonates with RPD larger than 10mm were examined by renal scintigraphy. Receiver-operating characteristic (ROC) plots were constructed to determine the accuracy of three indexes: fetal RPD, postnatal RPD, and SFU grading system. Results: A total of 193 infants were included in the analysis. Seventeen infants (8.8%) presented VUR, corresponding to 26 renal units. To discriminate between renal units with and without VUR areaunder the curve (AUC) was estimated by the ROC curve, which was 0.52 (95% CI=0.47-0.57), 0.58 (95% CI, 0.53-0.63), and 0.55 (95% CI, 0.50-0.60) for fetal RPD, postnatal RPD, and SFU grading system, respectively. There was no statistically significant difference between the indexes. The optimal threshold for fetal RPD was 7 mm with a sensitivity of 69% (95% CI, 48-86) and specificity of 45% (95% CI, 40-51), For postnatal RPD the respective figures were: 54% (95% CI, 33-73) and 72% (95% CI, 67-77) for the cut-off of 8.8 mm.

Conclusions: Our data shown that the magnitude of RPD is a poor predictor of presence of primary VUR. There was no significant difference in performance among the indexes. Objetive: We investigated the prevalence of renal calcification in children with autosomal ressecive polycystic kidney disease (ARPKD) and studied the metabolic changes thats could cause this complication.

Methods: 9 patients with ARPKD. 6 girls/3 boys; range age 2 m to 15 y. Criteria inclusion presence typical imaging findings: enlarged kidney and diffusely increased renal echogenicity and poorly defined renal margins on sonography; suggestive imaging features with positive results renal or liver biopsy, Results 7 patients, 5 girls and 2 boys, range of age 9-15 y, had CT scan renal clacification bilaterally. Without renal clacifications <1 year. 7 children renal calcifications, 7 sistemic hypertension, 4 portal hypertension and gastrointestinal bleeding and one renal colic. Renal insufficiency 6 patients, it was mild in 3 (GFR >50 ml/min/1,73 mt 2 ), moderate in 2 (GFR 30-50), and severe in one (GFR<30). All with renal insufficiency had distal tubular acidosis. Hypocitraturia urine 7 patients. Urinary calcium, uric acid, oxalates, and cystines normal in all. Tuberoussclerosis (TSC) -an autosomal dominant inherited genetic disorder -is characterized by development of hamartomatous growths in many organs.Two causative genes, TSC1 (chromosomal locus 9q34) and TSC2 (chromosomal locus 16p13.3) have been identified. TSC2 gene is adjacent to PKD1, the major gene for autosomal dominant polycystic kidney disease (ADPKD) on chromosom 16p13 and contiguous germline deletion of both genes results in severe polycystic kidney disease phenotype at birth. At 6 months of age bilateral abdominal masses were occasionally palpatedin a previously healthy girl. Ultrasonography demonstrated enlarged (approximately 15 cm) kidneys with multiple large cysts resembling those seen in ADPKD. Renal function and blood pressure was normal. Suspicion of tuberous sclerosis was raised due to numerous hypopigmented cutaneous macules on the trunk and extremities. Echocardiography demonstrated 2 rhabdomyomas in the left ventricle with no hemodynamic significance. An isolated juxtapapillary astrocytoma was found in the left eye. Her psychomotor development was normal with no history of seizures. Cerebral magnetic resonance imaging revealed multiple subependymal nodules with noobstruction of the cerebral fluid pathways. By multiplex ligation-dependent probe amplification (MLPA) a large DNA deletion was identified spanning from TSC2 exon 10 to PKD1 exon 46 permitting the diagnosis of TSC2-PKD1 contiguous gene syndrome. Cardiac rhabdomyoma and cutaneous manifestations were found in her father as well but no renal changes. At 3 years of age the girl is doing fine with ACE blockers against hypertension. Renal function is still normal. The size of the cardiac rhabdomyomas is diminishing while the cerebral and ocular hamartomasare unchanged. This additional report focuses TSC in an infant presenting with polycystic kidneys and cutaneous lesions. Improvements in ultrasound technology and the appropriate timing of antenatal ultrasound has led to refined prenatal diagnosis and enhanced accuracy of diagnosis of fetal renal anomalies and makes it possible to treat obstructive and/or refluxing uropathies before the onset of clinical symptoms.A retrospective review of 165 patients; 44 girls (26,7%) and 121 boys (73,3%) admitted to our clinic between January 1999-December 2006 with antenatal urinary anomalies were investigated to determine the urinary tract anomalies, and the follow-up results are presented. Routine prophylaxis was started at admision and the imaging studies were performed. The mean gestational age at detection was 28,4±5,87 weeks. The mean age of admittance was 32,95±29,63 days and the average follow-up period was 19,15±26,05 months. Antenatal ultrasonoghrapy examination showed anomalies in 220/330 renal units. Of these 220 antenatally observed renal units, 216 had postnatal urinary tract anomalies. Of these 216 postnatally observed renal units, 235 urinary tract anomalies were detected (multiple urinary tract anomalies in 48 patients) ( Table 1) . Fifty-two (31,5%) children had 59 surgical interventions such as; ureteroneocystostomy, pyeloplasty, nephroureterectomy, PUV resection. Eighty-one (49%) of our patients had urinary tract infection during follow-up and renal scar was detected in 58 (35%) patients. Acute renal failure developed in 6 patients and chronic renal failure developed in 3 patients and three patients died. We conclude that all infants with fetal urinary abnormalities should be evaluated, so that we can recognize and treat congenital anomalies that may affect renal function or cause urinay tract infection, renal scarring. The majority of patients with fetal urinary anomalies can be managed safely with close conservative follow-up. Fetal urinary tract obstruction at 50 days gestation (E50) produces small kidneys with cysts, whereas obstruction at 60 days (E60) generates large kidneys with cysts. In the present study, we investigated the mechanism for the generation of small kidneys by urinary tract obstruction at an earlier gestational age, E50. Fetal lambs underwent urethral and urachal ligation at E50 (n=17) or E60 (n=39). Fetal lambs were delivered by C-section 5, 7, 20 days after obstruction, or at term (145 days gestation). Unoperated kidneys of E50, E60, E80, and at term served as controls. The percentage cystic area of kidneys obstructed at E50 and E60 was not different 5 days after obstruction (17±5% vs 17±6%). After 7 days, however the percentage of cystic area became larger in kidneys obstructed at E50 (40±17% vs 23±5%), and was significantly larger 20 days after obstruction (51±18% vs 17±17%). Proliferating cells, detected by PCNA staining, were found in cysts and tubules of obstructed kidneys increasing toward term, and were more abundant in kidneys obstructed at E60. On the other hand, PCNA-positive cells in the nephrogenic zone were reduced in obstructed kidneys. The decrease was more prominent in kidneys obstructed at E50. Apoptotic cells, identified by TUNEL staining, were detected in the inner medulla of obstructed kidneys equally in kidneys obstructed at E50 and E60 during the fetal stage. At term, TUNEL-positive cells were rarely present in normal kidneys or kidneys obstructed at E50, but were found abundantly in the interstitium and occasionally in cysts and tubules of kidneys obstructed at E60. In conclusion, urinary tract obstruction at an earlier gestational age produces small kidneys by inhibition of mesenchymal cell proliferation, which may be due to compression by cysts.

A. Results: Detrusor hyperreactivity, most commonly in I and IV or V grade was found in 47.9% of VUR children. The maximum detrusor pressure was above 70 cm H 2 0. Detrusor-external dyssymetry was found in 17% of children, most frequently in grade I and IV or V grades, and detrusor-internal dyssymetry was recognized in 19.4% of children with VUR, most frequently in grade I and IV or V. In 12.5% of children with I-III grade of VUR cystometric capacity was reduced but 1 child with V grade had increased capacity of the urinary bladder. Glomerular filtration according to Schwartz equation was normal and independent of VUR grade. Decrease in osmolality below 800mOsm/kg H 2 0 in nocturnal urine was only detected in the group of children with IV and V grade of VUR,. There was no correlation between detrusor tension and osmolality of urine and glomerular filtration rate. Conclusions: 1). Dysfunction of the lower urinary tract, with detrusor hyperactivity was detected, as the most frequent dysfunction in 74% of children below 2 year old with I-V degree of VUR, 2). The maximun detrusor pressure in the voiding phase was highest in grade I and IV IV-V reflux children. Hypomelanosis of Ito was first described as a disorder characterized by unusual unilateral or bilateral macular hypopigmented whorls, streaks and patches. Subsequently, neurologic, skeletal and ocular involvement were described. Kidney involvement has only been exceptionally reported. Herein, we describe a case of a male infant with hypomelanosis of Ito and renal involvement. The patient was born at 40 weeks of gestation by cesarian delivery. The ultrasound scan at 34 weeks of gestation revealed bilateral enlargement of kidneys, decreased corticomedullary differentiation and cysts located in the cortical and subcapsular regions. These findings were confirmed at two months of life by CT scan. Skin examination showed hypopigmented linear and round diffuse lesions located on the right leg and arms. The ophthalmological examination showed anterior capsular and posterior subcapsular cataract of the left eye. As previously reported in other cases of hypomelanosis of Ito, the patient presented a transient leucocytosis (max 30.000/mm 2 ) during the first 8 months of life.The renal biopsy showed a classic picture of glomerulocystic kidney disease, whereas the skin biopsy confirmed the clinical diagnosis of Hypomelanosis of Ito.Three other cases of kidney disease in hypomelanosis of Ito have been reported. Of these, one case presented abnormalities of the glomerular basement membrane, and one case presented with polycistic kidney disease. The third case had renal cystic dysplasia with a histological picture containing glomerular cysts. Alltogether these reports suggest that genes involved in hypomelanosis of Ito are important for normal renal development and may be implicated in cystogenesis, when mutated. Here we report on a male newborn (birth weight 3070 g, length 51 cm) who presented with progressive edemas, oliguria and failure to thrive during the first week of live. On clinical examination he showed bilateral microcoria and decreased muscle tone. Laboratory work-up revealed large proteinuria (28 g/g creatinine), hypoalbuminemia (13 g/l) and renal failure ( Objectives. To investigate the incidence, nature, and management of associated genitourinary malformations in children with multicystic dysplastic kidney (MCDK).

Methods. In this retrospective study, we analyzed the medical records and imaging studies of 24 children with MCDK. In 20 children (83%) anomalies of the urinary tract were suspected prenatally in ultrasound studies. In the remaining 4 children the diagnosis of MCDK was made postnatally.

Results. The male/female sex ratio was 8: 16. The left side was involved in 11(46%) children.

Voiding cystourethrography was done in 14 (58%) children, the isotopic 99m Tc-DMSA scan of the kidney in 15 (63%). Urogential anomalies were present in 10 (42%) children. Among them, contralateral urologic anomalies were found in 3 patients (vesicoureteral reflux in 2 and hydronephrosis in 1), and ipsilateral in 8 (vesicoureteral reflux in 1, ureterocele in 3, and hydroureter in 2). Genital abnormalities such as uterine didelphys and hydrocele were found in 2 children. Fourteen (58%) patients underwent follow-up examinations with ultrasonography (mean follow-up 4.15 years, range 7 months to 12 years). Compensatory hypertrophy of the contalateral kidney was found in most children and decreased size of ipsilateral dysplastic kidney was found in 9 out of 14 children with follow-up. No cases of hypertension or tumor developed during the follow-up.

Conclusion. Ultrasound can be used safely to diagnose unilateral MCDKs and associated genitourinary malformation. Although the risk of hypertension and development of malignancy is low, follow-up evaluation of contralateral renal function and genitalia will be needed. In cases of hydronephrosis and/or urinary tract infection, voiding cystourethrography is necessary and possibility of association with genital anomalies should be considered until the puberty. 

A. Background: Ectopic ureter is a rare anomaly. Its incidence is at least four times higher in females and also more than 80% of the ectopic ureters drain duplicated systems in females. The most common presenting symptoms of an ectopic ureter are urinary tract infection and incontinence. Diagnosis is often delayed and may remain undiagnosed until adulthood. Case report: A 3-month-old girl was admitted to our hospital with the complaints of fever and discomfort. Her mother recognized intermittent dribbling of urine while changing her napkin. Physical examination revealed fever (38.3 °C), diaper dermatitis and intermittent dribbling of urine. Urinalysis revealed leukocytouria, acute phase reactants were elevated (CRP: 1.45, ESR: 27) and renal function tests were normal. The patient was hospitalized with the diagnosis of acute pyelonephritis. Tc99m Dimercaptosuccinic acid (Tc-DMSA) scan revealed an increase in the size of the right kidney and decreased uptake in the upper half of the same kidney. Ultrasound was performed with the suspicion of an ectopic ureter and it showed right duplicated kidney with marked dilatation of the upper collecting system. The ureter was also dilated in its whole length and ended ectopically distal to the bladder. Contrast-enhanced magnetic resonance urography (MRU) demonstrated right obstructed duplicated system with vaginal ectopic insertion of upper pole ureter.

Discussion: This case was presented to underscore the role of careful physical examination in the diagnosis of this rare anomaly that is by paying attention to the complaints of the family. Ultrasound is the initial, important diagnostic modality in these patients especially if done by experienced radiologists. The diagnosis can be confirmed with MRU by depicting the exact insertion of the ectopic ureter. Objectives of study: To evaluate the occurrence and severity of vesicoureteral reflux (VUR) in young infants with a history of mild prenatal hydronephrosis. The usefulness of voiding urosonography (VUS) in the diagnosis of VUR was also evaluated. Methods: Forty seven infants (31 males, 16 females) with a history of mild prenatal hydronephrosis, diagnosed between 21 st to 30 th week of gestation, were enrolled in the study. Postnatal ultrasound was performed within the first month of life. Voiding cystourethrography (VCUG) and at the same time, contrast-enhanced harmonic VUS was performed at the age of 1.5-2.5 months.

Results: The prenatal ultrasound revealed an anterior-posterior pelvic diameter of 5-7 mm in 33 fetuses and 7-10 mm in 14. Postanatal ultrasound showed an anterior-posterior pelvic diameter of 5-7 mm in 34 infants and 7-10 mm in 13. VUR was found in 9 of 47 (19.1%) infants (grade I: 2, II: 4, III: 3). The VUR was detected by both VCUG and VUS in 4 of 9 children, only by VCUG in 2 and only by VUS in 3 of 9 infants. The VUR that was missed by VCUG was more severe (grade II and III), compared with this one missed by VUS (grade I).

Conclusions: Even though prenatal hydronephrosis was associated with a quite important occurrence of VUR, this was of mild or moderate severity. Comparison between the two imaging modalities showed that the VUR missed by VUS were with no clinical significance (grade I), whereas the VUR missed by VCUG were more severe. Although further study is needed, VUS could be an alternative method, mainly in girls, in whom the imaging of the urethra is not necessary, thus avoiding the radiation exposure.

Early Treatment with Indomethacin in a Neonate with a Bartter Syndromea Case Report Neonatal BS is a rare genetic disorder characterized by sodium, potassium and chloride urinary wasting, hypokalemic metabolic alkalosis with hyperreninemia and hyperaldosteronism in the absence of hypertension and high level of urinary prostaglandins. Indomethacin therapy is controversial because of toxicity for gut and kidney. A premature boy of unrelated couple was born by cesarean section at 28 weeks because of early rupture of membranes and fetal distress. Birth weight was 900 g, length 36 cm and Apgar score 2/6/8. Pregnancy was complicated by severe polyhydramnios. Baby was mechanically ventilated for first 12 hours and treated with antibiotics because of suspected sepsis. Marked polyuria and dehydration were present from 1st week. Metabolic parameters revealed hypokalemia, hyponatremia and hypochloremic metabolic alkalosis. Serum creatinine was slightly elevated and GFR in normal ranges. Blood pressure was normal with raised plasma renin activity and aldosterone level. Sodium excretion via urine and level of renal and systemic prostaglandins were increased. Nephrocalcinosis was detected on US from 2 week. Additonally to electrolyte supplementation indomethacin was started on the 18th day at a dose of 1 mg/kg/day. In first 2 months child experienced 4 septic episodes, candida pyelonephritis and was operated because of bowel obstruction. DNA analysis of affected child found 2 new mutations in ROMK gene: P185L and Q289X in herited from parents who carried one mutation each. At 18 months height and weight are at 3 and head circumference at 50 percentile with slightly retarded psychomotoric development. He continues on 1.2 mg/kg/day indomethacin therapy. Blood electrolyte profile is normal without supplements. US shows no progression of nephrocalcinosis. Early treatment with indomethacin may prevent life-threatening complications and reduce the development of nephrocalcinosis. Nimuselide, a COX2 inhibitor is widely used in India for relief of pain and fever. We describe 6 cases of fetal renal abuse leading to neonatal renal failure due to maternal ingestion of Nimuselide in the third trimester of pregnancy. Results: All 6 patients were diagnosed as having renal failure in the first few days of life.There were 5 boys and one girl.. All the mothers had normal pregnancies except for oligohydramnios that was detected during the last 2 months of pregnancy in all cases.4 children presented with anuria from birth. The remaining two had non-oliguric renal failure with metabolic acidosis as the presenting feature in one and poor feeding and lethargy in the other. USG revealed normal sized kidneys. One patient also showed increased echogenicity. 3 out of the 4 anuric children underwent peritoneal dialysis for a period varying from 3 to 4 weeks without recovery of renal failure. The remaining 3 were managed conservatively. Two of these patients are now in chronic renal failure at ages 2 and 5 years. Only one patient recovered completely after 5 days of anuria. All the mothers had taken nimuselide in the last trimester for periods varying from few days to several weeks for relief of pain or fever. Some of them had taken multiple courses of short duration. The mother of the child who recovered completely had taken Nimuselide in the last 5 days before delivery. Renal biopsy done in one baby revealed renal tubular dysgenesis. Conclusion: Nimuselide intake in the last trimester of pregnancy can be associated with oligohydramnios and neonatal renal failure that can be irreversible. Renal tubular dysgenesis may be the underlying pathology. Objectives of study: PKD is the most common inherited renal disease. Aim of ours study was to analyse clinical and laboratory features of the different types PKD. Patients and methods: We described the clinical presentation of 47 children with PKD (26 boys, 21 girls) diagnosed in pediatric nethrology department between 1989 and 2007. The patient's age range was from 3 months till 18 years. We retrospectively studied the family histories, clinical and biochemical data (physical examination, level of arterial blood pressure, blood and urine creatinine levels, serum levels of Urea, glomerular filtration rate), ultrasonography, scintigraphy.

Results: The analysis of the family histories revealed ADPKD in 27 patients (14 boys, 13 girls), ARPKD in 6 (2 boys, 4 girls) and nondifferential PKD in 14 (10 boys, 4 girls) children. PKD diagnosed by antenatal ultrasound in 6 cases (2 ADPKD, 4 ARPKD).

The mean follow-up ADPKD were 4,4 year (range 1 -13 years), ARPKD -5,3 year (range 1 -14,5 years). Conclusion. Patients with ARPKD demonstrated the early beginning of an arterial hypertension and progressing chronic renal failure. One girl with neonatal form of ARPKD died. Chronic renal failure developed in 9 (19,1%) cases of PKD. Objectives: This prospective study was to answer the question on the need of long-term follow-up and correlation of renal functions with the age at surgery and grade of o.u. prior to surgery in patients after surgery of obstructive uropathy (o.u.). Methods: Selected biochemical markers of glomerular and tubular functions and ultrasonographic findings in 62 patients (40 boys) who underwent surgery due to uni-or bilateral o.u. of grade III. and IV. (age at surgery <12 months) in 1994-1997 were examined at mean age of 6.3±0.9 years. The results were compared to 32 healthy controls and/or to reference values according to age. Consequently, patients were devided into groups according to the age at surgery (0-3 months, 4-6 months, 7-12 months) and grade of o.u. prior to surgery. Results: Serum concentration of cystatin C (s-cysC) was significantly higher in patients when compared to control group (p<0.001). While s-creatinine was within reference interval in all patients, s-cysC was increased in 63.3% when compared to reference interval. Decreased tubular resorption and concentration ability was found in 67% and 26% patients, respectively. Non-specific aminoaciduria was detected in 42.9% patients. On ultrasound, 66.7% kidneys after surgery had residual dilatation of renal pelvis. The differences in renal functions in patients according to their age at first surgery were not significant except for u-NAG activity with significant negative linear trend with higher age at surgery. The grade of o.u. prior to surgery did not have significant influence on renal functions. Conclusions: Mild tubular dysfunction and slightly reduced GFR in the part of patients make longterm nephrologic follow-up reasonable. Our results support the trend of postponing early postnatal surgical intervention in patients with positive ultrasound screening of o.u. and normocreatininemia. Objectives of study: To evaluate, during almost five years of follow-up, the changes among preoperative and postoperative renal function in 46 infants (36M/10F) with prenatal severe hydronephrosis (HN) and UPJ obstruction. Methods: UPJ obstruction was diagnosed by a MAG3 renal scan, performed at 4-6 weeks of age to establish baseline differential renal function; Surgery was made if there was evidence of obstruction injury, and/or progression of HN and/or symptoms. The group was re-imaged 3 months after surgery, after 6 months, 1 year and then annually. Results: Initial differential renal function was moderate in 41.6% of males and in 30% of females and good in 58.4% and in 70% respectively. Also,75% of kidneys required surgery because of declining function, with mean differential renal function in the affected kidney of 32% that improved to 44% already at 3 months after pyeloplasty. There was no significant functional improvement, in the kidneys that underwent correction because of increased HN or symptoms and final renal function was >40%. After pyeloplasty T was >30 min. in 21% and 20-30 min. in 79% of cases (p<0.05) There was no statistically significant correlation between initial grade of HN and initial renal function. Surgical treatment was performed between 9-16 months of age and there was no significant difference in postoperative results, ascribed to patient age at surgery. Ma values, greater than controls at diagnosis, reduced at 18 months after surgery in all, but 16% of children.

During the follow-up, the mean Ccr and BP values were in normal range for age in all children.

Conclusions: Our findings showed improvement also in kidney with preoperative uptake less of 40%. This may be to explain in according to an inverse correlation between degree of renal dysplasia and gestational age.

Objective of study: is to determine the postnatal course and follow-up of children with fetal hydronephrosis. Methods: In 6 years period (2000) (2001) (2002) (2003) (2004) (2005) (2006) we followed 72 infants with antenataly detected hydronephrosis. All infants were submitted to ultrasonographic examination of kidneys and bladder. If indicated, the isotope renography, micturating cysto-urethrography, i.v.urography and MR were performed. Results: The diagnosis of hydronephrosis was established during 15 -39 th weeks of gestation by obstetritian. First postnalat ultrasound investigation was performed during neonatal period in most children (69%). In 48 (66,7%) infants we diagnosed idiopathic hydronephrosis, in 12 (16,6%) vesicouretheral reflux (VUR) grade II-IV, in 7 (9,7%) hypofunction of one kidney, in 2 (2,8%) ureteropelvic junction obstruction (UPJO), in 1 (1,4%) ren duplex and ureterocele, in 1 (1,4%) ampular pelvis and in 1 (1,4%) afunction of one kidney. After 6-12 months we found normal ultrasound in 35 (48,6%) children. The ultasound results were stable in 24 (33,3%) children and in 9 (12,5%) there was progression of hydronephrosis. Four (5,5%) infants underwent immediate surgery.

Conclusions: In a group of 72 infants with antenataly detected hydronephrosis the diagnosis was confirmed postnataly in 89% infants. More than 50% of infants required long term follow-up. In 5,5% the immediate surgey was required. This data support the need for antenatal detection of hydronephrosis. In the same period we followed up 207 infants with urologic abnormalities which were not detected antenataly.The fetal ultrasound is reliable screening method in detection of urologic abnormalities. The considerable number of anomalies which were not detected antenataly are the result of insuffitient use of fetal ultrasound investigation. Hemolytic uremic syndrome (HUS) is defined by acute renal failure, microangiopathic hemolytic anemia, and thrombopenia. Perinatal asphyxia (PA) may cause renal failure after birth and is often associated to disseminated intravascular coagulopathy (DIC) with platelet consumption. However, no biological investigation permits to distinguish clearly neonatal HUS from DIC. We report three neonates with renal failure due to different degrees of PA. They presented biological features compatible with HUS such as fragmentocytes (3%), thrombopenia (<50,000/mm3), anemia (<8 g/dl). Serum creatinine on day 5 was 293, 152, 372 mmol/L respectively, requiring peritoneal dialysis in one patient. Haptoglobin was undetectable for all three patients. Factor H and I were in the lower normal range; components of the complement system (C3, C4) and ADAMT13 activity were decreased. Two patients received daily fresh frozen plasma infusions over the first 4 weeks. Renal function improved in two patients until day 30; one patient has chronic renal failure. All other parameters suggestive for HUS were normal on day 12, 30, and 60 respectively. No severe neurological consequences were noted for either of them. PA may be responsible for multiorgan damage via ischemic lesions. Ischemia may result in endothelial cell injury, the crucial event for the development of thrombotic microangiopathy. We hypothesize that endothelial cell damage concomitant with PA may lead to a vicious circle resulting in consumption of platelets and plasma factors involved in hemostasis and/or fibrinolysis. Early use of fresh frozen plasma may correct these alterations. Renal biopsies might have been useful but are technically difficult in newborns.

In conclusion, PA and neonatal HUS are difficult to distinguish and endothelial cell damage may be a common pathyphysiological aspect and might requirespecific treatments. 

A. Medynska, M. Nalesniak, K. Kilis-Pstrusinska, D. Zwoliñska

Congenital posterior urethral valves (PUV) are the most common cause of lower urinary tract obstruction in male neonates. We aimed to review our experience with PUV children (24 boys) in respect to retrospective analysis of the clinical course of disease. We analyzed: ultrasound during pregnancy, age of disease onset, clinical symptoms at admittance to hospital, outcome. Average lenght of follow-up was 7,3 years, varying between 2 month and 20 years.Obstruction of urinary tract was suspected by prenatal ultrasound in 9 patients. The initial presenting symptoms were as follows: urinary tract infection 7 boys, failure to thrive 3 patients, increased abdominal circumference -2, abdominal pain 1, enuresis -3, acute renal failure 1, and chronic renal failure 14 children. In association with PUV renal dysplasia/hypoplasia in 4 patients, undescended testis 3, bladder trabeculation 4 were found. The diagnosis of PUV was confirmed by voiding cystourethrograms and/or cystoscopy. Primary vesicouretral reflux was documented in 7 pts. Hydronephrosis and/or megaureter were observed the most often in 14 boys. The diagnosis of PUV was established in 10 pts at the age of less 1 month, in 6 pts between 2 -12 months, and in 8 between 1-15 years. Surgery was performed in 7 pts in neonates period including primary valve surgical ablation and/or cutaneostomy vesicostomy. Chronic renal failure was diagnosed in 7 boys in first year of live. 4 of them progressed to end-stage renal disease. Globally during the follow-up 7 pts developed end-stage renal disease. 4 pts have done a graft. Only 5 boys survive without progression to chronic renal failure. The presentation of PUV is variable and currently antenatal detection is the most common mode. Outcome boys with PUV is poor. Patients need nephrologic assesment from birth. Background: Furosemide is among the 10 most frequently used drugs in the neonatal unit but few studies analyze the beneficial effect and complications in this patient group.

Objectives of the study: To analyze the therapeutic clinical effect and to document side effects of furosemide therapy in extremely preterm infants born <28 weeks gestational age (GA). Methods: Twelve infants born <28 weeks GA were prospectively included during the fall 2006. The following parameters were documented prior, during and after furosemide administration: Clinical status, serum/urine electrolytes, creatinine, albumin, blood gases and furosemide exposure. Ultrasound of the kidneys and a wrist radiograph were performed at 6-8 weeks to rule out osteopenia/rickets and nephrocalcinosis respectively. No statistical analysis were done due to the small study size. Results: General oedema, respiratory rate, apneic spells and oxygen supplementation decreased. Arterial/venous PCO 2 decreased and partial oxygen saturation increased indicating improved lung function. HCO 3 increased and pH decreased. Urinary excretion of sodium, potassium, chloride and calcium increased while phosphate excretion decreased. Serum sodium and chloride decreased and potassium increased initially. Six infants had electrolyte disturbances and metabolic alkalosis. One infant died during the study period. In the remaining 11 infants, 3 of 5 had worsening of their patent ductus arteriosis, 3 had osteopenia or rickets and 1 had nephrocalcinosis. The total side effect score was increased in the infants with the highest furosemide exposure.

Conclusions: This small study suggests that furosemide is beneficial in extremely preterm infants born <28 weeks GA and that the associated side effects correlate to the total drug exposure. We recommend caution for long term administration of furosemide. Conclusion: Although children in our study suffered significant neonatal HIE resulting in ARF, glomerular and tubular function recovered sufficiently to cope with increasing body mass and metabolic needs. Unlike reported studies, we did not find any significant evidence of CRI in the survivors of neonatal HIE and ARF. One with marginal microalbuminuria will need further observation. C was born after a monozygotic monoamniotic twin pregnancy (gestational age=34 weeks). She presented with twin-twin transfusion syndrome with hypotrophy (birth weight=2020g, other twin=2950 g), severe hypovolemia, anemia and acute renal failure. She required a blood transfusion, mechanical ventilation (5 days), and peritoneal dialysis (10 days). She recovered without bronchodysplasia but with chronic renal failure (creatininemia at 2 months=90 μmol/L). The following months were uneventful but, as usual in TTS, she exhibited growth retardation and slight mental delay compared to her twin. She reached terminal renal failure at 12 years of age and was successfully kidney transplanted. After age of 6 years, she presented with increasingly frequent and severe pulmonary infections predominantly in lower lobes of both lungs. After extensive explorations, the diagnosis of bilateral bronchiectasis was made. The search for classical aetiologies of such pathology was negative. The symmetric aspect and the absence of other etiologies lead to the consideration of bronchiectasis as a congenital pathology. Numerous publications demonstrate the role of the renin-angiotensin system (RAS) in renal and cerebral damages in TTS. Authors demonstrate the role or RAS in development of vasculature in fetus but also of cartilage and muscle in different organs including lung. Associations between TTS and lung pathologies need to be further investigated.

Urofacial ( The urofacial (Ochoa) syndrome (UFS) is a rare disease that occurs in both sexes and is more frequent when the parents are closely related. It has both urinary and facial abnormalities. UFS is a rare autosomal recessive disorder and a potential gene has been mapped to chromosome 10q23-q24. They present a bladder voiding dysfunction due to impaired neural communication between the bladder and the spinal cord, resulting in incomplete emptying of the bladder. This usually results in enuresis, urinary tract infection, hydronephrosis and in some severely affected patients, end-stage renal disease developed. The facial abnormality is a characteristic expression that, when these patients smile, their facial musculature inverts and they appear as if they are crying. We report a 15year-old girl who has inverted facial appearance, voiding dysfunction and vezicoureteral reflux. She had constipation and did the intermittan uretral cathaterization for five years. After a detailed evaluation, she was diagnosed as Ochoa syndrome due to inverted facial expression. We report this case, because early diagnosis of UFS is very important for early assessment and management of urinary problems to prevent development of chronic renal failure. We think that only a smile can give a strong high light for this unusual 'inverted' facial expression and patients can be screened earlier for severe voiding dysfunction. TAR syndrome is a congenital malformation syndrome characterized by bilateral absence of the radii and a thrombocytopenia. The known urinary anomalies with TAR are duplex ureter, dilatation of renal pelvis, horseshoe kidney, and functional problems like vesicouretheral reflux and pyelonephritis.

Case: Nine years old patient with TAR syndrome was admitted with a complaint of bright red urine repeated three times. The microscopic hematuria without dysmorphism of erythrocytes accompanied with no proteinuria were determined in repeated urine sample microscopy. IgA, ANA, anti DNA serology were negative. Urine culture was clean. Stone formation (6x7 mm) in the upper pole of the right kidney was established by the abdominal ultrasonography. Postoperative chemical analysis of the stone, revealed that it was consisted of oxalate monohydrate and dihydrate. But the patient discontinued his follow-ups afterwards for a year. In this period, he had macroscopic hematuria attack once. When he applied for the second time, he reported macroscopic hematuria. Cystoscopy was done for etiology. Many tortuous and engorged vessels were seen by this evaluation in the bladder mucosa ( Figure 1 ). There was no active bleeding point.

Result: In this report, kidney stone and telangiectasia found co-incidentally in the bladder of a patient with TAR syndrome during the examination of hematuria are discussed as there is no case report demonstrating nephrolithiasis and telangiectasia in TAR patients in the literature. Figure 1 : Many tortuous and engorged vessels in the cystoscopy. Antenatal hydronephrosis (ANH) is one of the common fetal abnormalities detected on ultrasound (US). The long-term renal prognosis for infants with mild to moderate postnatal hydronephrosis (HN) is unclear and controversial. A systematic review of the published literature was performed to determine an evidence based approach in infants with antenatally diagnosed HN and to identify those at risk of significant post natal nephro-uropathy (PNU). Key questions were identified. Does ANH predict renal tract pathology in neonates? What is the value of prophylactic antibiotics in infants with ANH? Can postnatal US diagnose significant PNU? When is the optimal time to screen infants postnatally? Which imaging modalities are necessary to diagnose the cause of the HN? How many neonates with ANH would need to be investigated to prevent one case of ESRF/CRF? A search strategy was formulated. Out of 362 titles only seven studies met the validity criteria for inclusion. The results indicate that antenatal US is a valid screening test for PNU (sensitivity 16%, specificity 98%), but is not a predictor of PNU. The detection rate of HN by US is the same whether it is done early or late in neonates. Two normal ultrasounds over a minimum of one month are required to screen for PNU. Infants with a renal AP diameter over 7mm are at risk of a significant PNU and should be investigated further. US is not a substitute for cystourethrogram or dynamic isotope studies to determine the cause of HN. None of the studies addressed the role of prophylactic antibiotics. There was insufficient data to calculate the total number of cases that would need to be investigated to prevent one unfavourable outcome (ESRF/CRF). High quality population based cohort studies with long term follow-up into adulthood are required to determine the optimum postnatal management of mild to moderate HN in infants with ANH.

Jeune Asphyxiating Thoracic Dysplasia: a Case Report Jeune Asphyxiating Thoracic Dysplasia (JATD) is one of the congenital hepatorenal fibrocystic syndromes. It is characterized by renal, hepatic, pancreatic abnormalities with associated skeletal abnormalities including a long and narrow thorax, metaphyseal irregularities, and shortness of the ribs and long bones. This report describes a pediatric patient with JATD developed end-stage renal failure. A 7-year-old boy was admitted with complaint of vomiting and pallor. He had dysmorphic appearance including trigonocephaly, short stature, long thorax and short limbs and fingers, polydactyly and fascial dysmorphism. Laboratory findings revealed severe anemia (Hb 3.8 g/dL), high BUN and creatinine levels (111 mg/dL and 7.9 mg/dL respectively) and normal liver tests. Abdominal USG showed a severe intrahepatic biliary tract dilatation and intraparenchymal cysts in liver, pancreas and kidneys. MR pancreatocholangiography was consistent with Caroli's disease. JATD should be considered when Caroli's disease exists with skeletal abnormalities.

Follow-up Antenatal Hydronephrosis: One Centre Experience The most common renal abnormality detected antenatally is hydronephrosis (1% to 5% of all pregnancies). In this paper, we report follow-up our patients with antenatal hydronephrosis (AH) between 2001 and 2006. Diagnosis of hydronephrosis was made >5 mm of antero-posterior diameter (AP) of the renal pelvis. AH was detected in 74 patients on antenatal ultrasound examination. Of the 74 patients with AH, 46 (62.1%) were found to have hydronephrosis postnatally and 34 (37.8%) postnatal scans were normal. In 17 of these patients (36.9%) had bilateral and 29 (63.1%) of these patients had unilateral hydronephrosis. In these patients with AH, uretero-pelvic junction obstruction (UPJ) 28 (60.8%), reflux 12 (26.2%), uretero-vesical junction obstruction 3 (6.5%), posterior urethral valves 2 (4.3%) and mega-ureter 1 (2.2%) were identified. In follow-up period, 2 (16.6%) patients with reflux, 19 (41.3) patients with UPJ were treated with surgery (p<0.05). In conclusion, UPJ was most important cause of AH and most of them were treated with surgery.

Hyponatremia and Renal Tubular Acidosis in Severe Vesicoureteral Refluxa Case Report

Sahlgrenska Academy, Department of Pediatric, Gothenburg, Sweden Case report: 1st child to healthy parents without heredity for kidney or metabolic disease. Antenatal bilateral hydronephrosis. Postnatal examination showed bilateral VUR grade V, normal urethra. Antibiotic prophylaxis was started, no urinary tract infection (UTI) occurred. Normal s-creat and s-Na + at 2 weeks of age. The electrolytes remained normal during the next 3 months. Normal growth. The boy was thirsty with high urine volumes. At 3 month of age feeding problems began with retarded weight gain. No vomiting or diarrhoea. At admission to the hospital the child was dehydrated, s-Na + 120 mmol/l, s-Cl -99 mmol/L, s-pH 7.11, bicarbonate 11 mmol/L, s-creat 36 μmol/L. CRP 8 mg/L, urine culture negative. U-Na + 10 mmol/L, u-pH 6.0, u-osmolality 214 mosm/kg. The anion gap was normal and there was no lactacidosis. The s-aldosterone was elevated 53,1 nmol/l, s-cortisone normal. Treatment included intravenous rehydration, Na + supplement and oral bicarbonate. Blood chemistry normalised and the child's general condition improved rapidly.

Conclusions. Children with severe reflux are at high risk for UTI but may also develop impaired tubular function with diabetes insipidus, renal tubular acidosis and hyponatremia. The mechanisms include down-regulation of vasopressin receptors and impaired distal tubular function. Close clinical monitoring of these children with regular blood chemistry and weight controls is important. Purpose: We aim to prospectively study the natural history of minimal to severe grades of Antenatal Hydronephrosis (ANHN) in our local Chinese population and correlate the renal pelvic diameter (RPD) with the outcome. Patients and methods: Cases of ANHN were prospectively followed up along a predefined protocol using US, MAG3 and MCU in all. Obstruction (PUJO or VUJO) was defined as a need for surgery based on symptoms and deteriorating function, not on MAG3 drainage time.

Results: 174 neonates were followed up for minimum of 5 years. Eighty percent had normal or minimal HN on postnatal scans (RPD 5-9 mm), 11.4% had mild (10-14mm) or moderate (15-19) HN and 8.5% severe HN (>20 mm). Seventy-eight percent infants had benign course; 6.9% had partial obstruction which improved; 11.5% had vesicoureteric reflux (VUR) one of which required surgery. Another 5.7% required surgery for obstruction. The ROC curve for obstruction requiring surgery showed optimal cut-off point of 18.5 mm (sensitivity 100%, specificity 99.2%). Prolonged diuretic T1/2 was not predictive of surgery. Severity of HN did not correlate with presence or grade of VUR. Fifteen patients developed UTI despite antibiotic prophylaxis and 7 had focal scars, all occurred in association with high grade VUR or obstruction.

The prognosis of infants with minimal or mild ANHN is good. However RPD is poorly correlated with VUR. The chances of obstructive lesions requiring surgery are high when the RPD is above 18 mm. In those with high grade reflux or obstruction, urinary tract infection may lead to renal scars.

Objectives of study: Cystinosis is a rare disease presented initially with renal Fanconi syndrome, and renal glomerular failure develops later in childhood. Without cysteamine treatment, patients affected with cystinosis uniformly died during childhood in the absence of renal replacement therapy (RRT). Cysteamine is not available here and in some other areas of the world. The aim of this paper is to describe a beneficial effect of acacia gum in a patient with cystinosis and chronic renal failure. Method: 9 years old girl with cystinosis presented with symptomatic uremia as she didn't receive cysteamine. Serum creatinine 7.4 mg/dl, blood urea 200 mg/dl. The girl was hospitalized and vomiting controlled with intravenous fluid and pyridoxine. Chronic dialysis was not available for her and the parents refused treatment with intermittent acute peritoneal dialysis. The girl was treated with a new therapeutic regimen (Therapy2006;3 (2): 321) combining the traditional conservative management of CRF (dietary and pharmacologic) with addition of Acacia gum (AG) 25 g/day as an urea lowering agent aiming at improving her condition without dialysis. Results: Treatment was associated with amelioration of the uremic symptoms and improved general well being. After 2 weeks of treatment, serum creatinine 1.9 mg/dl, blood urea 69 mg/dl. During 4 months of follow-up she continued in experiencing improved well being and urea levels was kept below 70 mg/dl without dialysis. Conclusion: It was possible to improve the health of patient with cystinosis despite the nonavailability of cysteamine and the appropriate RRT.

Objectives of study: The pattern of renal tubular disorder (RTDs) has been infrequently reported in the literature, and the pattern of RTDs in Iraqi and Arab children is not known. Methods: From June 2000 to August 2006, it was possible to evaluate 40 children with suspected RTD to determine the type of their tubular defect. There was evidence of RTD in only 35 patients; 22 males (63%) and 13 females (37%). Their ages at referral ranged between 8 months and 14 years (mean 4.8 years). In 4 patients with oculo-cerebro-renal syndrome, there was no evidence of RTD and one patient had hyperoxaluria which not a RTD.

Results: Seven types of RTDs were identified. The three most common disorders were: idiopathic hypercalciuria (37%), cystinosis (21%) and renal tubular acidosis RTA (21%). Four of the patients with RTA have proximal RTA, and four have distal RTA. Four of the patients with hypercalciuria have also significant hyperoxaluria >3 mg/kg/day. Conclusion: The pattern of RTDs in Iraqi children differs from the previous studies: In Germany the three most frequent disorders were cystinosis, XLHR, and idiopathic hypercalciuria.

Objectives of study: Few literatures reported the incidence of ocular abnormalities in chronic renal failure (CRF). The aim of this paper is to determine the incidence of ocular abnormalities in childhood CRF. Methods: From January 1993 to December 2005, 80 patients with CRF (at the University Hospital in Al Kadhimiyia) were examined to determine the presence of ocular abnormalitites. Fifty patients were males (62.5%) and 30 (37%) were female. Their age at referral ranged from 2 months to 18 years (mean 9 year). They were followed for a period ranged from 5 days to f years. Results: Corneal cystine crystals were the most common ocular abnormalities associated with childhood CRF observed in 6 patients with nephropathic cystinosis (7.5%). Congenital cataract & glaucoma were observed in 3 patients (3.75%) with oculo-cerebro-renal syndrome (OCRS). Congenital cataract & chorioretinal hypoplasia were present in 1 patient with OCRS. Hypertensive retinopathy occurred in 2 patients. Acquired cataracts occurred in one patient with Hinman syndrome in association with hypocalcaemia and non-compliance with calcium and onealphacalciferol supplementation. Retinitis pigmentosa in one patient with Laurence Moon Biedl syndrome. Bilateral optic atrophy in one patient with familial nephropathy associated with club feet. Proptosis in one patient with membranoproliferative glomerulonephritis. Conclusion: Ocular abnormalities are relatively common in childhood CRF occurring in approximately 19%. Objective: Hypocalcaemia has been reported as a complication of phototherapy especially in neonates. We studied the relation between serum calcium level and urine calcium to creatinine ratio in neonates under phototherapy. Method: 50 icteric newborns (30 males and 20 females) treated by phototherapy entered into study by non accidental sampling. The consent was taken from parents on admission. All were breastfed healthy newborns. Weight was checked and serum samples for calcium and bilirubin and urine aliquots for calcium, creatinine and osmoloality were sent on arrival (group I), after 48 hour of starting (group II) and 24 hour after discontinuing phototherapy (group III). Hypercalciuria was defined by UCa/Ucr >0.8, hypocalcemia was defined by serum calcium <8mg/dl in the term and <7 mg/dl in the premature. Chi2, ANOVA, Wilcoxon rank test and Spearman were used to compare frequency, means, median and correlation. P<0.05 was considered significant. Two groups were designed, pateints whose therapy were finished at least 12 months (group 1) and those either on therapy or less than 12 months passed from the last protocol of cytostat (group 2). Demographic data, cumulative dosages of anticancer drugs, history of other nephrotoxic agents, nephrectomy, radiotherapy and acute renal failure were recorded. We used CTC2 (1999) to evaluate renal function. Chi2 and Mann Whitney U test and biniary logistic regression were used to compare percentage, scoring and correlation respectively. P value less than 0.05 was considered significant.

Result: 58 out of 115 patients were in group 1 and 57 ones were in group 2. The mean of age was 11.86 years (±5.3 SD). The median (range) of therapy and termination was 36 months (1-156 months) and 1 month (0-12 month) in group 2 and 36 month (24-240) and 51 months (15-120 months) in group 1 respectively. The percentage of reversible renal failure, proteinuria, abnormal serum calcium and magnesium, metabolic acidosis and urinary concentration defect was higher in group 2. (Table 1) These differences were statistically significant (P<0.05). We found no correlation between CTC score and dosage of drugs, age, sex, history of radiotherapy or nephrotoxic agents (P>0.05).

Conclusion: mild to moderate tubular dysfunction has been observed in survivors of leukemia. Routine follow-up of renal functions is recommended. 

V. Tramma, K. Giourtzis, V. Fotoulaki, K. Nousia-arvanitaki Aristotle University, 4th Pediatric Clinic, Thessaloniki, Greece

Although CFTR is expressed in the kidney, patients with cystic fibrosis (CF) have not been reported to have major renal abnormalities with the exception of urolithiasis. The aim of this study was to determine renal function and the potential risk factors for renal stone formation in CF patients older than 10 years of age. The findings of metabolic evaluation of 4 CF patients having confirmed urolithiasis (mean age: 22,37±5,78) were compared with those of 27 CF patients without urolithiasis (mean age: 24,25±4,03) and those of 10 healthy volunteers (mean age: 22,13±4,98). Evaluation included plasma sodium (Na), potassium (K), chloride, BUN, creatinine, uric acid, calcium (Ca), phosphorus (P), magnesium (Mg) and parathormone (PTH). Twenty-four hour urine collection for creatinine, uric acid oxalates, Ca, Mg, K + , Na + and microalbuminuria was also performed. Glomerular filtration rate (GFR) was calculated and fresh urine samples were examined for the presence of crystals, erythrocytes, glycosuria and microorganisms. Patients with CF and urolithiasis showed significantly increased values of BUN (p: 0.012), PTH (p: 0.018) and GFR (p: 0.003), very low urine Mg levels (p: 0.014) and microalbuminuria (p: 0.034) as compared to CF patients without urolithiasis. There was no correlation of urolithiasis with hypercalciuria and hyperoxaluria. Furthermore, all CF patients showed significantly increased PTH levels (p: 0.032), very low urine Mg levels (p: 0.024) and microalbuminuria (p: 0.024) as compared to healthy volunteers.

Conclusions: Renal dysfunction was demonstrated in older CF patients, probably, secondary to the primary defect of renal chloride channels. Extracellular volume regulators, such as hormones, may also be implied. Urolithiasis may be the result of renal dysfunction. Conclusions: The morbidity of HSP had obviously increased in recent years. The familial cases, the initial symptoms of no palpable purpura at onset and the cerebral, pulmonary, cardiac and pancreatic involvement should be paid attention. Objectives of study: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organs and tissues including central nerve system, cardiovascular system and kidney. Although etiologic mechanisms of SLE are incompletely known, overproduction of immunoglobulin G autoantibody may contribute to onset of this disease. While still incompletely understood, the etiology of systematic SLE is considered to involve both genetic and environmental factors. We encountered two boys with severe SLE from unrelated families and analyzed polymorphisms of the gene that encodes cytotoxic T-lymphocyte associated (CTLA)-4, a protein important in T-cell activation and immune tolerance. Abnormal function of the gene may participate in causation of autoimmune disease including SLE, resulting in production of immunoglobulin against various self-antigens. Case report: In family 1, a boy showed serious cardiovascular complications associated with heart failure while his mother also had clinically active SLE including nephritis. A boy in family 2 developed severe renal complications and peripheral vasculitis accompanied by disseminated petechiae in the lower extremities; his paternal grandfather had died from fibrinous pneumonia caused by SLE.

Results: Analysis of the CTLA-4 gene indicated that the boy in family 1 and his mother possess a GG genotype in CTLA-4 exon 1 at +49 together with a 106-bp fragment length of the 3' untranslated region (UTR) in exon 4. The boy in family 2 also showed GG at +49. No association with disease activity was found for polymorphism of the promoter region in exon 1 at -318 in either family.

Conclusions: Disorders of the CTLA-4 gene, especially a GG genotype in exon 1 at +49 and/or 106bp fragment length of the 3'UTR in exon 4, may be involved in early development of SLE in Japanese children such as the boys described here. This disorder is transmitted mainly as X-linked trait, and is caused by mutations in the COL4A5 gene encoding α5 chain of type IV collagen. In some families, X-linked AS is associated with diffuse leiomyomatosis. We present clinical, pathologic and molecular-genetic findings in Japanese family with this inheritance mode of AS in association with leiomyomatosis. Case report and Results: AS was diagnosed in a one-year-old boy with recurrent aspiration pneumonia caused by esophageal stenosis from leiomyomatosis. He had macroscopic hematuria and bilateral cataracts. Diagnosis was confirmed by electron microscopy coupled with type IV collagen chain subtype staining in a renal biopsy specimen. Thickening and irregular contours of the glomerular basement membrane (GBM) and splitting of the lamina densa were evident by electron microscopy. Immunofluorescent staining for type IV collagen chains failed to show staining for α3 (IV), α4 (IV), or α5 (IV) in the GBM, associated with lack of α5 (IV) and α6 (IV) staining in the BM of Bowman's capsule. His mother, who exhibited esophageal leiomyomatosis and is heterozygous for AS, showed a discontinuous staining pattern for α5 (IV) along the epidermal BM. Genetic analysis in the boy revealed the deletion of the first two exon of COL4A6 together with deletion of the 5' end of COL4A5. Conclusion: Identification of an AS patient during infancy is extremely rare. Clinical manifestations, including macrohematuria, cataracts and leiomyomatosis caused by the large deletion involved COL4A5 to COL4A6, led to early presentation with AS. Functional voiding disorders of the bladder occur in the absence of any anatomic/neurological abnormality and present with wetting. Invasive urodynamic studies are discomforting, not easily available in emerging countries and costly. This study aims to validate non-invasive urodynamics. Children below 12 years, with possible voiding disorders evaluated prospectively. Non-invasive evaluation included history, examination, frequency volume charting, ultrasonography, urinalysis and renal functions. Micturating cystourethrogram was carried out for children with urinary tract infection. All children underwent invasive Urodynamic Studies (UDS) and the significance of association of the parameters of non-invasive assessment with invasive urodynamics was determined. The Chi square test was used for statistical analysis using the Epi 6 software. 34 children underwent invasive UDS. The commonest abnormality was detrusor instability (DI) in 21 (61.7%). Dysynergic voiding (DV) noted in 6 (17.6%), lazy bladder in 2 and an occult neurogenic bladder in 2. The study was normal in 3. 

Repressing the Disease Progression may be 1.5 mg/kg/day or More Background: Henoch-Schoenlein purpura is classified into the small vessel vasculitis. There may be no reliable indicator of the disease activity. Steroid treatment (1 mg/kg/day of prednisolone) has been thought of as a means with which alleviate abdominal pain. However, this dose seemed to be not effective to intervene the disease progression to nephritis. Objectives: Forty-three Japanese children with Henoch-Schoenlein purpura were enrolled in this study. Fibrinogen degradation product E-fraction (FDP-E) value was measured once or twice a week in the patients. Coagulation factor XIII was simultaneously measured in 36 of the patients in the early phase of illness. With an aim to alleviate abdominal pain, 0.7-2.0 mg/kg/day of prednisolone had been administered to 15 of the patients. Results: At presentation, only 16 of the 36 patients had low factor XIII activity. On the contrary, 33 of them had elevated serum FDP-E value.

Longitudinal FDP-E measurement revealed that patients whose FDP-E value normalized within the second weeks of illness had minimal risk of nephritis. In this group, 2 of 28 had microhematuria.

In the other patients group with prolonged (after fourteen days of illness) elevation of FDP-E values, 8 of 15 had nephritis. Furthermore, 7 of 8 had proteinuria after three months of illness. These 8 patients who had received prednisolone therapy with less than 1.5 mg/kg/day in the early phase of illness. The other 7 patients with 1.5 mg/kg/day or more prednisolone therapy had no nephritis. Summary: The disease activity of HSP and HSPN might reflect the duration of elevated serum FDP-E. More than 1.5mg/kg/day of prednisolone may repress the disease progression to nephrits. Background: All major organs are involved more or less in thalassemia and most of them have been studied thoroughly in previous literature. Renal system involvement has not been scrupulously scrutinized yet. Method: In a randomized prospective study, renal findings of 58 children and young adults, aged 3-24 years, with thalassemia major (group 1) were compared to other 50 cases of thalassemia intermedia (group 2). Blood urea nitrogen, serum creatinine, uric acid, calcium, phosphate, urinalysis, and sonographic findings were evaluated. Results: Mean age was 17±3.5 years in group 1 and 18±3.0 in group 2. Mean serum ferritin level was 3503±201 ng/ml in group 1 vs. 871±81.8 ng/ml in thalassemia intermedia group (p<0.05). 92% of subjects of group 2 had received or was on hydroxyurea at the time of evaluation. Serum uric acid was significantly higher in patients with thalassemia intermedia ( Conclusion: Significant renal involvement is not a frequent complication in children and young adults suffering from thalassemia. Hyperuricemia and microscopic hematuria is more common in thalassemia intermedia than thalassemia major.

Case: a 13-year-old female patient was born at term (weight 3750 g, lenght 51 cm) and for aspiration of amniotic fluid required resuscitation and mechanical ventilation for 17 days. Perinatal hypoxia was a cause of her acute renal failure but dialysis was not needed. Patient's follow-up during next 12 yrs showed mild form of chronic renal failure (CRF) without hypertension: serum creatinine (SCr; range during follow-up [rdf] 95-112 μmol/l), glomerular filtration rate (GFR; rdf 66-73.8 ml/min/1,73 m 2 ) and P (rdf 30-180 mg/24 h). At the age 13yrs we performed renal biopsy (RB) because girl's P and SCr increased (358 mg/24 h, 139 μmol/l, respectively) and GFR decreased (51 ml/min/1.73m 2 ). RB showed C1q-nephropathy (C1qN) with focal glomerular sclerosis and hyalinosis. C1qN is a rare disease and as a first diagnostic step is differentiation against lupus nephritis. Progression of C1qN to CRF is infrequent. Probably two renal diseases were a cause of CRF in our patient -hypoxic renal damage during neonatal period and C1qN. Objective: Renal dysfunction has been reported in survivors of neoplastic disease. Early diagnosis of renal damage may decrease the morbidity in those with partial or complete remission. We studied the frequency of nephrotoxicity in pediatric patients whose therapy were completed. Method: 108 pediatric cancer patients (44 F, 64 M) who were at least one year off therapy, enrolled in a prospective cross sectional study from 2003 to 2005 in oncology department of Ali Asgar Children Hospital. Demographic data, cumulative dosages of anticancer drugs, history of other nephrotoxic agents, nephrectomy, radiotherapy were recorded. Fasting blood and urine samples were collected to calculate fractional excretion of Mg, Ca, P, Upr/Ucr, Clcr, urine osmolality and blood gas analysis. Result: The mean of age was 12.9 years. 80 out of 108 patients had lymphoproliferative malignancies (group 1) and 28 had solid tumors (group 2). The mean of therapy was 35.44 month. Treatment was discontinued for 52.48 month in average. The median of blood Ca, P, Mg, bicarbonate,and Cr were 9.3 mg/dl, 3.6 mg/dl, 2.1 mg/dl, 22.65 mEq/L and 0.6 mg/dl, respectively. The median of fractional excretion of Ca was 0.81% this rate was 7.47% for P excretion and 2.4% for Mg excretion. Clcr was 135.3 ml/min/m 2 in median. The medians of urine osmolality was 850 mosmol/kg/H 2 O. The median of urine protein to urine creatinine ratio was 0.07 mg/mg. These values were not different between two groups (P>0.05) but urine concentration was defective in solid tumors group (P=0.001). Mild to moderate nephrotoxicity was seen in 52.8% of cases. Using binary logistic regression we found no correlated factor (P>0.05).

Conclusion: mild to moderate tubular dysfunction has been observed in survivors of chemotherapy. Routine follow-up of renal functions are recommended.

The study is to discuss the treatment of Hemolytic Uremic Syndrome (HUS) after acute stage. Methods: there were 13 children who lived through acute stage of HUS then continued treating. Besides angiotensin converting Enzyme Inhibitors (ACEI) and early restriction of protein intake, the study was to use therapeutic schedule according to clinical classification, response to Prednisone and pathological manifestation, which referred to clinical classification diagnosis and treatment of child with glomerulus disease (The Program) established by Nephrology Group in Pediatric branch of Chinese Medical Association (CMA). Results: after 5 months to 12 years follow-up 4 mild type children maintained the normal blood pressure and renal function and urine examination, except for 1 recurrence. In 9 gravis type children 6 maintained the normal blood pressure and renal function and urine examination, another 3 children who manifested as durative abnormality of urine examination developed into end stage renal failure (ESRD) and died in the 5th, 8th and 13th month at last. Another 4 gravis type children untreated after stage of HUS died in the 27th day to 48th day of the course. Conclusion: it could improve the prognosis of children after acute stage of HUS evidently to use therapeutic schedule according to clinical classification, pathological manifestation.

Objective: To find the prevalence of hematuria in patients with thalassemia major. Methods: Of total 1000 patients with thalassemia major under regular blood transfusion, 500 cases were randomly selected. History was reviewed and physical examination was done. Urinalysis was performed in all the patients. In those with hematuria (5 or more RBC/HPF) or suspicious to hematuria (3-4 RBC/HPF) second urinalysis was done at the next transfusion time. More investigations were done in those with persistent hematuria. Results: The patients had age range of 6 months to 32 years and male to female ratio was 1.05. Hematuria was detected in 20 (4%) and suspicious in 33 patients (6.6%). Sixty four percent of the patients with hematuria were female and it was persistent in urinalysis in 90% of cases. In 81% of the patients with hematuria, blood transfusion was started before the end of first year. In those with hematuria or suspicious to hematuria, 4% had sterile pyuria and 16% had proteinuria (these figures were 2.1% and 1.4% respectively, in those without hematuria). Hypertension was not detected, but 2 patients had secondary diabetes mellitus. Conclusion: Hematuria is not uncommon in patients with thalassemia major and is more prevalent in girls and in those with early transfusion. Background: it has been widely recognized that cyclosporine A (CyA) is a useful immunosuppressive drug in renal transplantation. Although it has been also accepted that CyA is an effective drug for pediatric nephrotic syndrome in the past two decades, the effective serum concentrations are not revealed. The functional roles of CyA has been reported that CyA inhibits the production of interleukin 2 (IL-2) in vivo and in vitro. Aim: in this study, we investigated the correlation of serum concentrations of CyA levels with IL-2 levels in pediatric nephrotic syndrome cases. Methods: seven children (6 boys and 1 girl, mean age 9.5±4.24 years) with minimal change nephritic syndrome were enrolled in this investigation. CyA (mean dose, 3.49±0.88 mg/kg/day) was administrated in two divided doses before meal with or without administration of predonisolone. Blood samples were collected just before, 1, 2, 3 and 4 hours after administration of CyA. The serum concentrations of CyA and IL-2 were measured immediately. Results: the peak blood concentrations of serum CyA were observed at 1 hour after administration. The concentrations of serum IL-2 levels reduced at 1 hour after administration of CyA, and kept the same levels during 4 hours afterwards. The serum concentrations of CyA which inhibited more than 80% of the serum concentrations of IL-2 required 500 ng hr/ml. Conclusions: we confirmed that CyA inhibited the production of IL-2 in children with nephrotic syndrome. These findings suggest that the necessary serum concentrations of CyA to maintain the sufficient suppressive rate were more than 500 ng hr/ml in pediatric nephrotic syndrome. This study aimed to evaluate the circulating angiotensins in female adolescents with type 1 diabetes (DM1) and to compare with the results obtained in healthy age-matched adolescents to disclose possible changes in plasma peptide concentrations that could be related to microalbuminuria and metabolic control. Patients were divided as female adolescents with DM1 (n=25) and adolescent age-matched controls (n=18). Diabetic patients were evaluated at our Endocrinology Center and healthy adolescents were selected from our Primary Care Unit. Plasma levels of Angiotensin (Ang) I, Ang II and Ang-(1-7) were determined by radioimmunoassay. Glycohemoglobin and microalbuminuria were also measured. Results were expressed as medians or means and standard deviation. Kruskal Wallis was used for median comparisons and t-test for means. The level of significance was p<0.05. Adolescent DM1 patients exhibited high levels of glycohemoglobin (9.5±0.4%). Microalbuminuria was detected in 5 (20%) patients with a disease duration of 8.4±0.7 years. Angiotensin concentrations were significantly increased in DM1 patients (p<0.05 compared to controls) and Ang-(1-7) levels were 4-fold higher than control values. On the other hand, the levels of Ang-(1-7) in microalbuminuric patients were significantly lower than in non-microalbuminuric diabetic adolescents (p<0.05). The comparisons between ratios of Ang-(1-7)/Ang I and of Ang II/Ang I suggested a predominance of Ang II formation rather than Ang-(1-7) in microalbuminuric diabetics when compared to normoalbuminuric patients. Our results showed an overall increase of angiotensins in a young female diabetic population, and further suggested a pathophysiological role for Angiotensin-(1-7) in DM1. 

The pediatric nephrologist is often faced with the difficulty of determining adequate iron supplementation in children with chronic kidney disease (CKD). Soluble transferrin receptor (sTfR) and the sTfR to log(ferritin) ratio (sTfR-F index) have been proposed as markers of iron deficiency (ID) independent of inflammation; however, their relationship with C-reactive protein (CRP) and their age dependency have not been established. We therefore embarked on a prospective study of 436 healthy children undergoing minor surgery to determine reference ranges for sTfR (Dade Behring N-Latex sTfr analyser, Dade Behring BN Prospec) and sTfR-F index. We studied the relationship between CRP and ferritin, transferrin, sTfR and sTfR-F index. We also compared the relationship between mean corpuscular volume (MCV) and ferritin, sTfR and sTfR-F index in 205 children. Results: for ages 0. .0001, 0.0050) with MCV, which we used as a marker of ID in the absence of a non-invasive gold-standard; however, only sTfR-F index, but not ferritin, transferrin and sTfR, was independent of CRP. This study shows that ferritin, transferrin, and sTfR, but not sTfR-index, are dependent on acute phase reactions. It is therefore hypothesized that sTfR-F index provides a more useful marker for monitoring the iron status in CKD patients. Conclusions: Low osmolality is a crucial factor to facilitate water absorption at least in the rat small intestine, while the absorption of sodium may be influenced by the concentration of sodium and glucose. (definition ICCS). Standard treatment consisted of general advice on voiding and drinking habits, alarm treatment and occasionally vasopressin. Constipation was diagnosed on clinical considerations (history, stool charts, physical examination, occasionally X-ray). All patients received general instructions according to bowel habits. Laxatives were prescribed when the patient was diagnosed as constipated. Treatment goal was daily bowel movements. Treatment results were evaluated 3 months and 2 years after discharge. Results: 151 patients were included. Mean follow-up was 2.2 yrs. Overall success rate (full response) was 80.8% (3 months) and 72.6% (2 years). Laxative use: 11.2% (n=17) of the patients received laxatives, 88% (n=133) did not. In 1 patient information was lost. There was no significant difference in success rate between the laxative group compared with the non-laxative group (p=0.14, chi-square). Treatment modality: 6.0% (n=9) received general advice only without laxatives, all but one had a full response. 90.1% (n=136) were treated with advice and alarm, 16 (10.6%) of them received laxatives. Response to alarm treatment was 82.5%. No significant difference in success rate between the laxative and non-laxative group (p=0.13, chi-square). 1 patient was dry after vasopressin and laxatives. Conclusion: the majority of patients with MSE can achieve nocturnal continence without laxatives. Constipation treatment with laxatives may be supportive, but is not essential in the treatment of MSE.

Aim: Hypocalcemic tetany is a known complication of plasmapheresis. We studied the changes in ionised and total calcium, and magnesium concentrations during plasmapheresis, with and without supplementing the replacement fluid with calcium and magnesium. Methods: Plasmapheresis was carried out by using 4.5% human albumin solution (HAS) with or without supplements for the first 85% of the exchange, and fresh frozen plasma (FFP) for the last 15%. We measured ionised and total calcium and total magnesium at the beginning and end of the HAS, and after 15 minutes of FFP infusion. Results: We undertook 31 pairs of plasmapheresis runs with and without supplements in 11 children who had a variety of renal conditions. During the exchange with unsupplemented HAS, the total calcium fell from 2.02 to 1.70 mmol/l (CI 9.9-20.3, P<0.000), the ionised calcium fell from 1. have raised significant problems in minor surgeries. But the developmental mechanism of PONV is not clear until now. Previously, we have experienced a case with IHN and PONV who showed extremely high plasma antidiuretic hormone (ADH) level at the onset of IHN and that elevated ADH level induced by minor surgery was supposed a trigger of IHN and PONV. In this study we investigated various values including plasma ADH in cases taking kidney biopsy in order to clarify the mechanism of IHN and PONV. Methods: Fifteen patients taking percutaneous kidney biopsy were study subjects (mean age 10.5 years). Plasma ADH, serum electrolytes and osmolality were measured before and 4-5 hours after kidney biopsy. Urine samples were collected to measure electrolytes and osmolality. Results: High plasma ADH level (19.9±8.33 pg/ml) was observed in 9 out of 15 subjects (60%). Serum sodium level dropped significantly in these cases. Six of 9 cases showed PONV, we divided all 15 cases into 2 groups: PONV group and non-PONV group. The result was that plasma ADH level was significantly high in PONV group. Conclusion: Our study make it clear that elevated plasma ADH level is frequently seen in children taking kidney biopsy and suggest that hydration with hypotonic saline solution after surgery is inappropriate because of the risk of developing IHN. It also become clear that high plasma ADH level might lead to PONV as the same mechanism seen in motion sickness. It is suggested that ADH secretion by stress after minor surgery is associated with not only IHN but also the onset mechanism of PONV. Polyarteritis nodosa (PAN) occurs more commonly in patients with familial Mediterranean fever (FMF) and visceral hematomas are seen in almost half of the patients. We report here a 14 year-old girl with PAN and FMF presented with multiple visceral hematomas. The patient was on colchicine therapy for four years because of FMF but uncompliant to therapy. She addmitted with the complaints of fever, malaise, abdominal pain and artralgia lasting for two months. She was pale and extremely cachectic with atrophic muscles of extremities. She had fever, hypertension, hepatosplenomegaly and arthritis. She had anemia with normal renal and hepatic function tests, albumin levels, and electrolytes. Multiple hypoechogenic mass lesions were detected on liver and bilateral kidneys on ultrasonography and computerised tomography and diagnosed to be hematomas by laparascopic examination. Urinalysis, hematological tests for bleeding and blood marrow examinations were normal. Bacterial cultures and serological tests did not reveal any infectious agent. Serum complement levels were normal with negative antinuclear antibody, anti-DNA, p and c antineutrophil cytoplasmic antibodies. Renal angiography showed multiple aneurysms in bilateral renal arteries leading to the diagnosis of PAN. She was successfully treated with intravenous pulse methylprednisolone followed by oral perdnisolone and oral cyclophosphamide together with colchicine and antihypertensive agents. She has been followed up for four years without any complaints and normal laboratory and radiological findings except multiple scar formations on kidneys on DMSA-renal scanning. Results: The stone-free rate was 86% after one ESWL session. The above rate increased to 92% and 96% after the second and the third session respectively. Regarding surgical treatment with PCNL, the overall stone-free rate was 93%. In 3 children initially treated with PCNL, an ESWL session was performed later successfully, for residual calculi. Open surgical removal was required in 9 children with structural anomalies. The patients with staghorn calculi underwent nephrolithotomy combined with ESWL in cases of residual fragments. 12 patients underwent ureterscopic procedures to address ureteral stones and complete fragment removal was obtained. No major sideeffect were observed, during the above procedures.

Conclusions: It seems that the advances in instrument technology provide a variety of safe and effective methods in the management of paediatric urolithiasis. The incidence of open surgery has thus fallen. Minimally invasive methods must form the first choice of treatment, while open surgery should be undertaken mainly in cases of coexisting congenital abnormalities. In all children the following parameters were estimated: a) timetable of NE, b) Feeling/volume chart (frequency and biggest quantity of urination=functional capacity of bladder), c) ultrasound of urinary tract (size of kidneys, bladder capacity, bladder wall thickness, postvoiding residual urine) and d) urodynamic parameters (uroflowmetry and water cytometry). The UD bladder parameters were then correlated with the US and voiding diary findings. Results: All children had sufficient data registered to allow reliable analysis. UD studies showed that children with mild PNE had normal urodynamics findings, US parameters and voiding diary findings as well. UD studies reveal a relatively high incidence of instability in children with moderate and mainly in those with serious NE.

Conclusions: In children with PNE, urodynamics did not have a significant additional value compared to baseline diagnostics and it should be avoided. On the contrary, findings from urodynamic studies in children with serious NE show that it has a useful role in this type of enuresis evaluation and management. Objectives of study: Hyperlipidemia, especially when started during early childhood will increase the risk of atherosclerosis. It is also a major risk factor for allograft nephropathy and post-transplant hyperlipidemia, so its diagnosis and treatment is highly suggested. In this study we have evaluated the effect of hemodialysis on the lipid profile of children with end stage renal disease (ESRD). Methods: Twenty-two children with ESRD who were on maintenance hemodialysis in Shiraz pediatric hemodialysis unit were studied. They were asked not to take greater than 30% of their total daily calories as fat at least 1 month before sampling. After a 12-hour overnight fasting and before starting dialysis, blood samples were taken for lipid profiles. For each patient with total cholesterol, TG or LDL-C levels more than 95th percentile for age and gender or HDL-C level less than 35 mg/dl, was defined as dyslipidemia.

Results: Nineteen out of 22 children (86.4%) had abnormal lipid profiles. Atherogenic factor of TG/HDL-C ratio more than 5 as a major risk factor for cardiovascular disease was in 86%. Conclusion: Dyslipidemia is common in hemodialysed children. So, hemodialysis set-up change and antilipimic medication, and replacement of L-carnitinine is recommended for correction of dyslipidemia in this group of patients. Objectives of study: Bipolar renal length measurement is an integral part of the assessment of urinary tract in childhood, and is routinely performed on ultrasonography and renal scintigraphy investigation. Correlation between kidney size measurement on ultrasonography and dimercaptosuccinic acid (DMSA) scintigraphy is not well recognized. The purpose of this study was to comparison renal size measured by DMSA scintigraphy and ultrasonography to find if there is acceptable agreement between renal lengths by these two methods. Methods: As cross sectional retrospective study, 90 patients enrol in this study and their DMSA scan results and kidney ultrasonography reports compared. The agreement between renal size measured by two methods for left and right kidneys were evaluated separately using Bland-Altman Plot. Pearson's correlation coefficient was used to examine their correlation. Statistical significance was calculated by paired-student t-test. The same tests were used to for kidneys with normal DMSA scans.

Results: Correlation coefficient showed close correlation between kidney length measured by ultrasound and DMSA scan, but there were significant differences between two methods (paired t-test, p<0.0001). Comparison between renal size measured by ultrasonography and DMSA scan using the methods of Bland & Altman plot in all patients and the group with normal kidneys showed a systematic bias of about +6.5 mm for left and +6.3 mm for right kidneys. Conclusion: Despite of close correlation between DMSA scan and ultrasonography for kidney length measurement; kidney size is overestimated by about 10 percent in DMSA scan study and this matter must be considered in practice. Medical treatment of cystinuria is often considered disappointing. Patients undergo frequent surgery which is often followed by early relapse. The aim of our study was to prospectively evaluate, in a paediatric population, the efficacy of a conservative medical approach for long-term treatment of cystinuria, to prevent the formation of new renal stones and reduce the number and dimension of pre-existing stones. Twenty-one stone former cystinuric patients were treated with a combined approach which included cystine-binding drugs. Free and bound urine cystine levels were routinely measured every four months. Drug dosage was adjusted in order to maintain a steady free urine cystine level below 100 mmol/mmol creatinine (a three fold increase of normal level). In the 19 patients who completed the study, renal stone episodes were reduced from 0.28 to 0.03 episodes/year, and in several patients the number and dimension of pre-existing renal stones were reduced. During the entire follow-up, percutaneous lithotripsy to remove an obstructive stone was required in only one subject. No relapse was observed 12 months after treatment. The dosage required to achieve target levels was very closely correlated to patient body weight: older children required a lower dose to achieve target levels.

In conclusion: medical management of cystinuria is feasible. The treatment must be personalised, at least in pediatric age. The amount of required drug is strictly depending from body size. It is mandatory to obtain a low free urine cystine level before any invasive procedure to reduce the risk of early relapse. Objective: To study the pathophysiology of nutcracker syndrome (NS) and to assess the role of the upright position imaging and superior mesenteric artery (SMA) angle measurement in the diagnosis. Methods: Doppler US findings in 23 children with NS and in 26 healthy control subjects were compared. The mesenteric angle, peak velocity (PV) and anteroposterior (AP) diameter of the left renal vein (LRV) at the hilar and aortomesenteric portions were measured in both the supine and upright positions. The means ±SD of the SMA angle, AP diameter and PV ratio between the two portions were calculated and cut-off levels for the diagnosis of NS were established. Results: The diameter and PV ratios were significantly different between the patient and control groups both in the supine and upright positions (p<0.001). Differences (D) between the supine and upright positions were also significant for the diameter of the LRV at the aortomesenteric portion, diameter ratio and SMA angle in both groups. Upright position imaging revealed comparatively narrower SMA angles and more pronounced entrapment findings in patients with NS. The SMA angle measurement had a sensitivity of 69.6% and a specificity of 61.5% in the supine position and 87.0% and 76.9% in the upright position when the cut-off values were set to less than 41° and 21°, respectively.

The upright position has significant effects on the LRV hemodynamics and angle of SMA both in patients and healthy subjects. SMA angle measurement may be a useful adjunct parameter in the diagnosis of NS. ). In addition, a statistically higher rate of pathological abnormalities on renal biopsy was noted in the group with microscopic hematuria combined with proteinuria and also in cases with more severe hematuria.

Conclusions: School urinary mass screening has greatly contributed to diagnosing chronic renal diseases. Continuous medical observation is required when abnormal urinalysis is observed, and a more aggressive medical approach such as renal biopsy should also be performed if necessary. This study compared the outcome of children with proliferative LN (WHO class III/IV) using a new protocol comprising pulse intravenous methylprednisolone, MMF +/-cyclosporine, with standard prednisolone and cyclophosphamide/azathioprine. Method: Twenty-three children with proliferative LN (age range at diagnosis 3.7-18.6 years) who were followed up for 6.9-4.5 (range 1.3-21.0) years, were included in this retrospective study. Group I (n=11) received prednisolone with cyclophosphamide and/or azathioprine. Group II (n=12) received the combined MMF protocol with MMF dose of 1200 mg/m 2 /day. Poor outcome was defined as death or chronic renal failure. Survival analysis was performed using the log-rank test. Effect of treatment on growth at last follow-up was assessed using height standard deviation score (HtSDS). Differences between the groups were analyzed using the Mann-Whitney and Fisher's exact test.

Results: At last follow-up, significantly more Group I compared to Group II patients had higher serological activity as defined by low serum complement C3 (50% vs 0% respectively, p=0.014).

In addition, 8-year actuarial survival was higher in Group II (100%) compared to Group I (61%). All the Group II patients achieved complete remission of proteinuria compared to Group I (0.01±0.06 vs 0.79±1.0 g/d/1.73 m 2 respectively, p=0.002). Group II patients also had lower HtSDS on long-term follow-up compared to Group I (-0.26±1.05 vs -1.96±1.73 respectively, p=0.025). Conclusion: Combination immunosuppressive protocol involving MMF +/-cyclosporine resulted in better renal outcome in children with proliferative LN without compromising on growth. This regimen allowed steroid tapering to alternate day dosing without increasing lupus activity. Background: A full dose of corticosteroid is required to induce complete remission (CR) in steroidsensitive nephrotic syndrome (SSNS), unless it is possible to taper and discontinue along with the course after CR. However, the mechanism of this change in steroid sensitivity remains unknown. P-glycoprotein (PGP) has a function to eliminate given corticosteroids from cytoplasm, which results in inducing corticosteroid resistance. Therefore, we analyzed a drug delivery perspective using the real-time polymerase chain reaction (PCR) of multiple drug-resistant gene 1 (MDR1; encoding PGP) messenger RNA (mRNA) expression. Patients and methods: Fourteen patients with steroid-sensitive nephrotic syndrome (SSNS; male/ female: 14/0, Age: 1-23 years old; mean 10.4) were enrolled in this study. MDR1 mRNA gene expression of peripheral blood nucleated cells (PBNC), before and after CR (a total of nineteen sets of blood samples), were quantified using real-time PCR and then carried for analysis. Results: The MDR1 mRNA levels before CR were variable in each patient. However, there was an apparent decrease in the MDR1 gene expression of PBNC after CR (P<0.003).

The results suggest that PGP may play a role in the ability to taper corticosteroids after CR in SSNS. : 6 week prednisone 60 mg/m 2 /day + 6 weeks 40 mg/m 2 every other day). All other patients (B) received daily prednisone 1.5-2 mg/kg/day for 8 weeks and 30-50% of initial dose for 1 week, followed by alternate day steroids (41 week) with tapering by 2.5 mg every 6-8 weeks down to 2.5-5 mg. "Frequent relapses" (less than 2 months after discontinuation of initial steroid therapy or of first relapse therapy) were treated with chlorambucil 0.15-0.2 mg/kg/day for 8 weeks and half of this dose for 6-10 months.

Results: Seven patients (with long treatment) were lost to follow-up and 48 were studied. Six of 11 (55%) of A had a relapse 4.6±1.7 months after the end of initial therapy; 3 became infrequent and 3 frequent relapsers. 19 of 37 (51%) of B relapsed 7.8±1.3 months after the end of initial therapy; 14 became infrequent and 5 frequent relapsers. Frequent relapsers (27% in A and 14% in B) were treated with chlorambucil and all but one achieved long remission (>1 year). Conclusions: First relapse occurred later after onset of SSNS in patients with long (50 weeks) as compared to short (12 weeks) initial steroid therapy but the time interval between the end of initial therapy and the first relapse and the proportion of relapsers were similar. Longer initial therapy may result in a lower number of frequent relapsers. Nearly all patients had long remissions periods that were, however, achieved at the expense of early administration of chlorambucil. Conclusions: the medium age of pts with metabolic stones was found to be higher than the medium age of pts with infectious stones. The familial occurrence of kidney stones was found to be important 46%. The ultrasonographic examination is the most important one. The stones composed by calcium oxalate and calcium phosphate were found to have the highest percentage. Metabolic abnormalities were found in 75% of patients and hypercalciuria was the most common disorder. Hypocitraturia is considered to be a risk factor the calcium stones. In an attempt to explore the new treatment for the childhood-onset intractable steroid-dependent nephrotic syndrome (SDNS), we have recently performed the treatment with high-dose mizoribine (MZR), the inhibitor of inosine monophosphate dehydrogenase, and suplatast tosilate dimethylsulfonium STD), a selective Th2 cytokine inhibitor, which were both made in Japan. MZR has been commonly used for the treatment of frequently relapsing SDNS in Japan at a dose of 3-4 mg/kg/day (maximally 150 mg/day) divided into two doses (Kidney Int 58: 317,2000). We used high-dose MZR (mean: 10.1 mg/kg/day) once before morning meal for 9 adolescent patients with frequently relapsing SDNS who had been treated with long-term cyclosporine (CsA) resulted in moderate to severe CsA nephropathy. With this treatment for 2 years, seven out of 9 patients weaned off CsA and experienced less relapses without apparent adverse effects by high-dose MZR. STD is a both IL-4 and IL-5 inhibitor and commonly used for childhood asthma. We used STD at a dose which is for the treatment of asthma for 13 children with SDNS (mean 9.2 years) without previous CsA treatment. After one year follow-up with STD treatment, the relapse rate of nephrosis was decreased from 1.54±1.20 to 0.15±0.56 per year (p=0.0008 by Wilcoxon signed-ranks test), where as the dosage of orally given predonisolone was also decreased from 0.19±0.21 to 0.04±0.05 mg/kg/day (p=0.0187 by Wilcoxon signed-ranks test). Objectives of Study: To evaluate the efficacy and safety of long-term CyA treatment for pediatric SLE patients. Pediatric SLE patients in their teens suffer from many relapses and severe side effects caused by steroid and cyclophosphamide. There have hardly been any reports on the long-term CyA treatment in children. Methods: We retrospectively compiled 6 cases of childhood-onset SLE female patients (mean: 12.1 years) admitted to our department from 1995 to 2004. The initial treatment was methylprednisolone pulse therapy followed by prednisolone (PSL). At the onset, 4 patients had class 2 lupus nephritis and 2 showed class 3. After several relapses, CyA was added and used for 20 to 68 months. The dose of CyA ranged from 2.8 to 4.9 mg/kg/day, and the target trough level from 50 to 80 ng/mL. Results: Under this low-dose CyA treatment, 5 patients had no relapse while 1 had a relapse after 49 months. In all patients, PSL was reduced to alternate day treatment (mean: 10.8 mg/2 days), and 3 patients under 14 years gained the target height. Of all patients, 5 developed hypertrichosis, 1 gingival hyperplasia, 1 transient elevation of s-Cr with acute gastro-enteritis. Although 1 case had elevated s-Cr after 20 months of CyA treatment, it returned to normal level within 3 months after the cessation of CyA. Five patients had second biopsy after 2 years, and 2 showed mild tubulointerstitial (T-I) changes. Two had third biopsy after 5 years and both showed mild T-I changes only. The presence of T-I changes had no relation to s-Cr, u-beta2 MG and u-NAG. Conclusion: Low-dose CyA treatment might be an effective and safe second line treatment for SLE patients with many relapses in teens. It is also important to perform renal biopsy periodically to detect CyA-induced renal damage which hardly shows any abnormalities in blood or urinary tests. 3 

Hypersensitivity to inulin is rare; two cases of food allergy and some cases of allergy after inulin infusion have been reported. An 11-year-old boy suffering from severe IgA nephropathy (IgAN) is reported with both anaphylactic reaction and concomitant relapse of his nephropathy due to inulin infusion, used for measuring GFR 2 years after first symptoms. Pruritus, sibilants and cough were observed during a first renal function test. Prick and intradermal tests were negative for inulin. The patient presented with pallor and asthenia during a second inulin infusion performed under dexchlorpheniramin, leading to immediate infusion stop. He was read mitted because of fatigue and nausea; acute renal failure was diagnosed 4 days after inulin infusion. A drug-induced acute interstitial nephritis was first suspected. However, due to the presence of macroscopic hematuria and proteinuria, a renal biopsy was performed and showed acute proliferative relapse of IgAN. Few data are available about inulin-induced hypersensitivity. Chandra described anaphylaxis and cardiorespiratory arrest immediately after administration of sinistrin. A retrospective study of all recorded cases of hypersensitivity associated with renal function tests was performed by our pharmacovigilance unit. 6,328 tests using inulin clearance were realized both in adults and children; 31 patients experienced side effects which were divided into 3 groups: respiratory symptoms, rash and general signs. Most side effects were minor and no life threatening complication occurred. The underlying mechanism of inulin hypersensitivity is not well known. Although 55% of patients with inulin-associated hypersensitivity underwent a first renal function test, we can speculate that presensitization with food inulin may occur, sometimes leading to severe problems such as in our patient with IgA-mediated immunological dysregulation. . We have previously demonstrated a composite heterozygous NPHS2 mutation of both V165X and R168H in a Chinese patient with SRNS. However, it is not clear the molecular mechanisms of mutant podocinlead to proteinuria. Some evidences proved the possible interaction between podocin and TRPC6. This study explored the effects of mutant podocin on the free cytosolic Ca2+ and apoptosis of podocyte in order to clarify the possible causative mechanism of mutant podocin. Methods: 1. The pDsRed2 N1-wild/mutant podocin was constructed by using site-directed mutagenesis.

2. Mouse podocyte clone was cultured and transfected with pDsRed2 N1-wild/mutant podocin. 3. Free cytosolic Ca2+ was measured using the fluorescent indicator, fluo 3-AM.

Results: The low level of free cytosolic Ca2+ was detected in normal podocyte and the transfected podocytes with R168H mutant podocin. The V165X mutant podocin increased the free cytosolic Ca2+more evidently than the over-express podocin in transfected podocytes. Podocyte apoptosis were not detected in the Blank-vector (just pcDNA 3.0) transfected podocytes and normal podocyte. The V165X and R168H mutant podocin increased the podocyte apoptosis more evidently than the over-express podocin in transfected podocytes.

Conclusions: The V165X mutant podocin might induce podocyte apoptosis via the increment of free cytosolic Ca2+. However, whether the increment of free cytosolic Ca2+ is induced by TRPC6 and the involved signal pathway should be further investigated.

Y. Xing, Q. Fan, J. Ding

Objectives of study: Podocytes slit diaphragm (SD) associated molecules (nephrin, podocin and CD2AP) play a critical role on maintaining the integrity of glomerular filter. VEGF is produced by podocyte, and acts on endothelium and podocyte itself. But, it is not clear whether there are some relationships between VEGF and SD associated molecules. Our study detected the expression of SD associated molecules and VEGF in adriamycin (ADR) nephrotic rats. Methods: The ADR rat was established by ADR injection. Distributions of SD molecules and VEGF were detected by immunochemistry. The mRNA and protein of SD molecules and VEGF was examined by real-time PCR and Western, respectively. Nephrin phosphorylation were detected by immunoprecipitation. Results: Distribution of nephrin, podocin and CD2AP changed evidently, and the staining intensity of VEGF decreased evidently. Nephrin mRNA increased at day 7, and returned to the normal at day 14 and 28; podocin and CD2AP mRNA constantly increased from day 3 until day 28. The protein of nephrin increased at day 7 until day 28; podocin was dramatically upregulated at day 7, and thereafter recovered again, but was downregulated at day 28; CD2AP prominently increased at day 14 and day 28. Tyrosine phosphorylation of nephrin was decreased evidently at day 28, and VEGF mRNA did not show significantly changes at any time points observed. However, VEGF protein reduced significantly from the 7 th day, and also reduced evidently at days 14 and days 28. Conclusion: The abnormality of nephrin, podocin and CD2AP may be one of the mechanisms that lead to proteinuria in ADR-induced nephrotic rats. The occurrence of proteinuria in ADR rats may be also associated with the reduced VEGF protein, which may be related with the reduction of nephrin phosphorylation. These results suggested there may be some relationship between VEGF and SD molecules.

The Objectives of study: Mutations in genes encoding structural proteins of slit diaphragm can lead to nephritic syndrome. Just recently, another gene TRPC6 mutation was identified in autosomal dominant FSGS. TRPC6 encodes ion channel protein TRPC6, whose expression has not been clarified completely in kidney. This study aims to explore the expression and distribution of TRPC6 in normal human, mouse and rat renal tissue and the mouse podocyte clone (MPC5). Methods: Distributions of TRPC6 in normal human, mouse and rat renal tissue and cultured podocyte was observed with immunochemistry staining. The mRNA expression of TRPC1, 2, 3, 4, 5 and 6 was detected by using RT-PCR. The protein expression of TRPC6 in human, mouse and rat renal cortex and differentiated MPC5 was detected with Western.

Results: TRPC6 showed weak staining in glomeruli and strong in renal tubules and vessels in human kidney, however, strong in glomeruli and was mainly distributed along the capillary loops and mesangium in mouse and rat kidney. The staining of TRPC6 was observed in differentiated MPC5, which is distributed evenly on the cell membrane. The specific PCR band of TRPC1, 2, 3, 4, 5 and 6 was detected in mouse kidney and differentiated MPC5. The sequence of the amplified PCR products is same as that published in Genebank. The specific 106Kda protein band of TRPC6 was detected in normal human, mouse renal cortex and differentiated MPC5. Conclusion: The expression of TRPC6 was verified in normal human, mouse and rat kidneys and in differentiated MPC5. These results will benefit for further screening the possible mutation of TRPC6 in acquired nephrotic syndrome, and investigating the relationship between TRPC6 and the proteinuria-related podocyte molecules. Methods: Twenty children with KD (13 boys and 7 girls, aged from 3 to 78 months) were enrolled in our study. Kidney sizes (including kidney length and kidney volume) were measured during acute stage in these patients. Twenty age-and sex-matched healthy children and 15 febrile children served as healthy controls and fever controls. Left kidney length and age were used for correlation analysis and analysis of covariance. Results: Kidney lengths in patients with KD were significantly larger than those of healthy children (p<0.001). The mean SD score of kidney length was 2.54±0.97 for these patients (p<0.001, vs -0.23±0.82 in normal control). Kidney volume analysis yields the similar result (51.83±17.93cm 3 vs 35.62±11.24cm 3 , p=0.001). There was no kidney enlargement in the fever controls. Up to 70% of the children with KD have absolute nephromegaly (>mean+2SD). This incidence is as frequent as that of lymphadenopathy and extremities change, the 2 diagnostic criteria of KD. Conclusion: These results confirm the presence of large kidneys in the children with KD and also provide another useful indicator for KD diagnosis if the diagnostic criteria is not yet well established. 

During renal inflammation macrophages infiltrate the renal parenchyma, and their number correlates with the intensity of inflammation. Macrophage migration inhibitory factor (MIF) was described originally to be a product of T-cells and macrophages. MIF plays an important role in renal tissue injury. To our knowledge, the studies that assessed the role of macrophages in acute renal infection were few and the role of MIF was not evaluated. The aim of this study was to assess MIF in UTI and compare the urinary excretion of MIF in pyelonephritis, cyctitis and also control group to find a non-invasive and sensitive method to differentiate them. In this prospective case-control study 31 pediatric patients with UTI (25 patients with acute pyelonephritis, 8 patients with acute cystitis) and 40 healthy children were recruited. Urine MIF concentration was quantitated by ELISA and corrected for urine creatinine. The mean ratios of urine MIF/Cr were calculated as 66.14 (SEM=23.78) pg/μmol creatinine in acute pyelonephritis, 1.58 (SEM=0.59) in acute cystitis and 1.85 (SEM=0.35) in healthy individuals. Urine MIF/Cr ratio was significantly higher in pyelonephritis than the ones in acute cystitis (P=0.0001) and control (P=0.0001). ROC analysis was demonstrated that urine MIF/Cr ratio could considered potentially useful index to detect acute pyelonephritis [P=0.0001, area under curve (AUC)=0.959]. The optimal cut-point of 5.39 pg/μmol creatinine for urine MIF/Cr ratio could potentially separates acute pyelonephritis patients from healthy individuals (sensitivity and specificity of 92% and 92.5%, respectively). The underlying histopathological characteristics in biopsied renal diseases are of great importance in determining the long-term prognosis and provides useful information in clinical practice. Ethnicity seems to play a critical role in the epidemiology of biopsied renal diseases The aim of this study is to provide data of clinical manifestations of biopsy-proven native renal diseases in Iranian children.

In this retrospective study, 476 Iranian children who were diagnosed as renal disease between 1980 and January 2003, were evaluated. Diffuse and focal mesangial proliferative glomerulonephritis was present in 31.5% of all biopsies performed. MPGN, FSGS and MCD were observed in 9.2%, 10.2% and 13.4% The most common clinical syndrome at any age is nephrotic syndrome (50.4%), followed by nephritic syndrome (13.8%), nephrotic-nephritic syndrome (13.4%), recurrent macroscopic hematuria (7.3%), asymptomatic urine abnormalities (AUA) (7.7%) and azotemia was seen in 6.7% of patients. Mesangial proliferatiove GN (18/70=25.7%), Poststreptococal GN (15/70=21.4%) are the most frequent pathologies with acute nephritic syndrome presentation. The most frequent causes of AUA were mesangial proliferative GN and HSP. Thrombotic microangiopathy (HUS) was the most prevalent cause of ARF. Inthis study, chronic tubulo interstitial nephritis (33.3%) and Alport (13.3%) were the most common causes of CRF presentation in our patients.

In conclusion, MPGN remains the most common histopathological subtype in children with renal biopsied disease. The incidence of FSGS continues to be high in Iranian children. The aim of this study is to assess postnatal kidney volume development and to compare the intrauterine and extrauterine kidney growth curves in premature infants. One hundred neonates were enrolled in this study. All infants had their kidney volumes measured by renal ultrasound examination. Group GA consisted of 44 neonates whom were evaluated within 48 hours after birth, and their gestational ages were used in the analysis. Group CA included 56 premature infants born before 34 weeks of gestation and was evaluated 14-96 days after birth, and their conceptional ages were used in the analysis. Left kidney volume, body weight, body height and age were used in the correlation analysis. Kidney volumes in Group CA infants were significantly larger before 31 weeks of age, but smaller after 31 weeks of age than those of Group GA infants (P=0.001). There was a significantly better growth in body weight (P=0.001) and body height (P<0.001) in Group GA infants. However, a larger kidney volume was noted in Group CA infants with the same body weight (P<0.001).

Conclusion: Chart of postnatal growth of normal kidney volume before 40 weeks of conceptional age in premature infants is presented. Our data suggests that intrauterine growth may have a regulatory influence on kidney growth, and the reduced kidney volume in the premature infants may start from the early extrauterine period. Objectives of study: To illuminate the role of Prohibitin (PHB), a tumor suppressor which inhibit cell proliferation by repressing E2F-mediated transcription, in tubulointerstitial fibrosis (TIF). Methods: Renal biopsy specimens were obtained from 48 children with primary glomerulonephritis. PHB and α-SMA proteins expression were detected by immunohistochemistry. Subcellular location of PHB in NRK-49F was detected by confocal microscope. Changes of PHB protein and mRNA expression in cells upon TGF-β1 stimulation were detected. After transfected with PHB plasmid, cell cycle and α-SMA protein and mRNA expression in cells treated with or without TGF-β1 were detected. Results: PHB protein was found at normal renal tissues, with a positive distribution in interstitial cells and tubular epithelial cells. PHB was down-regulated in tissues with TIF and negatively correlated with TIF degrees (P<0.05). PHB is majority located at cytoplasm as well as at nucleus in NRK-49F. PHB protein and mRNA expression in cells were decreased when treated with TGF-β1, and the effects were both time-dependent and dose-dependent. Extraneous PHB inhibited cells proliferation induced by TGF-β1, and PHB over-expressing cells failed to enter the cell cycle compared with non-transfected cells (P<0.01). α-SMA was not expressed in control cells while de novo expression of α-SMA in cells upon TGF-β1 stimulation was increased. Overexpression of PHB did not affect basic α-SMA expression but dramatically repressed TGF-β1-initiated α-SMA expression (P<0.01).

Conclusions: Extraneous PHB suppresses renal interstitial fibroblasts proliferation and cell phenotypic change induced by TGF-β1, which indicates PHB as a potential target to halt TIF progression. Results: The prevalence of urine abnormalities of first screening was over 5.00%, and that of the second screening was about 1.00%. The prevalence was different with various methods. The specificity of method B was higher than method A. Testing two urine samples for each child had higher specificity. The direct cost of method A and B was -1.70 and -2.90 RMB, respectively. For screening twice, the corresponding cost was no more than -1.90 and -3.00 RMB, respectively. Using method A to screen twice for each child was convenient and economical, which also reduced the false positive rate effectively. The prevalence of urine abnormalities of junior highschool children was significantly higher than that of elementary school-children in XH and the peak point was seen at the point of 12 years old. However, there was no significant difference between children in JA and YP. More than 10 months of follow-up diagnosed 2 cases of IgA nephropathy.

Conclusions: Urine abnormalities of school-children could be detected through urine screening at school. For Shanghai, method A with screening twice was convenient, economical, and could reduce the false positive rate effectively. Objectives: Angiopoietin-like3 protein (ANGPTL3) is involved in lipid metabolism and angiogenesis. The present study was to examine ANGPTL3 expression in human kidneys with proteiuria, in adramycin rats (ADR), and in puromycin induced podocyte damage. Methods: Immunohistochemistry was performed on kidney biopsies from children with MCD, MN, FSGS, TBMN. In ADR, ANGPTL3 expression was determined by quantitative real-time RT-PCR in glomeruli and tubuli dissected from frozen section of kidneys with laser microdissection system. In MPC5, a conditionally immortalized mouse podocyte cell line in vitro, ANGPTL3, perlecan and agrin were detected through real-time PCR with the induction of puromycin. Detachment assay was performed in podocytes tranfected by ANGPTL3-pcDNA3.1. Results: In human kidneys, co-labeling showed ANGPTL3 expressed in the cytosol of WT1 positive cells. Quantitative computerized analysis showed that ANGPTL3 in glomeruli in MCD and MN were significantly higher than that of TBMN, FSGS respectively (p<0.05). In ADR, ANGPTL3 in glomeruli increased significantly at 21 st or 28 th day (p<0.05) after adriamycin injection compared with control. And the expression of ANGPTL3 in glomeruli was correlated with 24 h urinary protein (r=0.81, p<0.05). In MPC5 both protein and mRNA expression of ANGPTL3 on podocytes were up-regulated with the induction of puromycin. In podocytes transfected by ANGPTL3-pcDNA3.1 the expression of perlecan or agrin increased significantly compared with control (p<0.05). The attachment ratio was shown 95.7%±3.3% 24 hs after puromycin treatment on podocytes transfected by ANGPTL3 compared with 38.6%±4.7% on normal podocytes, and 27.4%±3.5% on untransfected podocytes. Conclusions: ANGPTL3 is predominantly expressed in podocytes which could be involved in podocyte damage and the development of proteiuria. (1), IV (1) and III (1), respectively. Only one patient had microhematuria. We found that 5 of them had a very low C3 serum levels. Clq and C4 deposits were all strong positive in 6 renal tissues.

Our findings suggest that biopsy should be strongly considered in this patient population. The significant renal involvement (Class III, IV, or V LN) could be found in SLE patients with very lower proteinuria with or without hematuria. Patients in BFB group received computer-assisted biofeedback program while those in DDAVP group took Minin. Both therapies were carried out for 1 month and then 3 months follow-up was taken. Parameters of follow-up included enuresis diary-urine flow rate and AQP2 in urine.

Results: 50 PNE patients were recruited (26 boys, and 24 girls), whose mean age was (8.4±0.9) years. At the end of treatment and three months later, total effective rates in BFB group were significantly higher than those in DDAVP group. Uroflowmetry findings showed that in BFB group maximum flow rate, voided volume and ratio of coordinative detrusor-sphincter contraction increased after treatment. Ratio of normal flow curve increased at second follow-up (p<0.05). In DDAVP group voided volume and voiding time decreased after treatment. Ratio of normal flow curve and coordinative detrusor-sphincter contraction had no change after treatment. Two bands of AQP2 (29 000 and 43 000) were detected in the morning urine. Density of patients bands was significantly lower than that of the controls. Density of 29 000 bands in DDAVP group after treatment were significantly higher than that before, but there was no difference between datas before and after treatment in BFB group.

Conclusions: BFB and DDAVP are both effective therapies for PNE in children. BFB is helpful in correcting voiding dysfunction and DDAVP can increase AQP2 protein in the urine. With higher effective rate within four month, BFB is strongly recommended. Objective: To describe the clinical course of non-parasitic chyluria in a Thai pediatric case. This is the first report in children.

Results: The 7-year-old boy presented milky urine lasting for one year. Urine tests showed heavy proteinuria (protein to creatinine ratio 9.1 mg/mg), lipiduria (triglyceride 29 mg/dl). The proof of a pronounced hypertriglyceriduria led to the diagnosis of chyluria. His renal function was normal. Numerous red cells and lymphocytes were observed in the urine, and postprandial cystoscopy revealed milky cloudy urine emanating from right ureteral orifices. Retrograde pyelography demonstrated pyelolymphatic backflow. Serum immunoglobulin G4 for Wuchereria bancrofti and circulating filarial antigen in the peripheral blood were negative. Chest x-ray, abdomen computed tomography and intravenous urography did not demonstrate abnormal mass or malformation. Proteinuria and lipiduria ceased before sixth week of a medium-chain triglyceride-rich diet. There was no recurrent chyluria after 12 weeks of MCT-rich diet were completed. Conclusion: In non-parasitic chyluria with unknown etiology, the low-fat diet with MCT supplementation alone is effective. The prognosis is excellent. There was a significant improvement of WAZ comparing data at admission and at the end of follow-up (p<0.001). There was also a significant improvement of WHZ comparing data at admission and at the end of follow-up (p=0.02).

Only 9 (2.3%) patients presented with a WHZ less than -2.00 at the end of the follow-up. Conclusion: Children with primary VUR presented an improvement in somatic growth with medical management.

Objective: The aim of this study is to investigate the clinical practical value of using Doppler ultrasound to detect renal blood flow in renal parenchymatous diseases of children.

Methods: The renal arteries, segmental arteries and interlobar arteries were detected by Doppler ultrasound. The parameters were peak systolic velocity (Vmax), minimum velocity in diastole period (Vmin), Vmax/Vmin (S/D), resistive index (RI) and pulsatility index (PI). There were 30 cases of healthy children, 20 cases of acute poststreptococcal glomerulonephrits, 20 cases of primary nephrotic syndrome and 15 cases of chronic renal failure. Results: The Doppler renal blood flow in normal school children was high velocity and low resistant type. 15 typical cases of acute nephritis with edema and oliguria appeared low velocity and high resistant type, RI, PI and S/D of all renal arteries were significantly increased, Vmin are significantly decreased (P<0.05). After 2 to 3weeks all parameters returned to normal. During edema period and convalescence, the renal blood flow of primary nephrotic syndrome is low resistant type, RI, PI and S/D of segmental arteries and interlobararteries were significantly decreased (P<0.01). The feature of low circulating blood capacity was not alleviated even though edema was vanished and urine output was increased. The Doppler in chronic renal failure was high resistant and low velocity type. RI, PI and S/D were all significantly increased, Vmin were significantly decreased (P<0.01). When RI was great than 0.8, the extent of damage in kidney function was serious and the prognosis was bad. Conclusion: Renal blood flow provided a new non-invasive method for clinic diagnosis and evaluation of the prognosis in children renal parenchymatous diseases. We concluded that the DMS is an important cause of congenital nephrotic syndrome. The outcome of our patients was poor and most of our patients died before 5 years old.

Objectives: The antiphospholipid syndrome is defined by the association of arterial/venous thromboses or obstetrical fetal loss with the presence of antiphospholipid antibody. This syndrome may be primary or secondary, particularly in association with systemic lupus erythematous. This study is to examine the frequency of anticardiolipin antibodies and the association between anticardiolipin antibodies with some symptoms in children with lupus nephritis. Methodology: Twenty-five children with lupus nephritis from 03/2006 to 11/2006 in Department of Nephrology, Children's Hospital o 1 were included in the study. We find the relationship between anticardiolipin antibodies with hematologic and renal involvement. Results: Anticardiolipin antibodies was positive in 11 patients (44%), 6 for anticardiolipin IgM antibody (24%), 7 for anticardiolipin IgG antibody (28%). There was a positive correlation between the presence of anticardiolipin antibodies and thrombocytopenia. In 11 patients with positive anticardiolipin antibodies, 3 patients had MTA on renal biopsy. Conclusion: Anticardiolipin antibodies are associated with thrombocytopenia and MTA. Aim: The methodologies for quantitating urinary calcium excretion have not been standardized. The aim of this study was to compare urinary calcium/osmolality (UCa/Osm) ratio with calcium/creatinine (UCa/Cr) ratio and to assess the correlation of both ratios with daily urinary calcium excretion for the diagnosis of hypercalciuria in children.

Patients and Methods: 364 children aged 6-14 years (mean 9.4±2.2 years) were included in the study. They were randomly selected from previous study's larger patient population. Non-fasting, second morning urine samples were collected from all children. Children were divided into two main groups: 1) 180 children with UCa/Cr <0.21(mg/mg) and 2) 184 children with UCa/Cr <0.21. 24-hour urine samples were collected from the second group, who were further divided into two subgroups: 2a) 113 children with daily calcium excretion <4 mg/kg/day and 2b) 46 hypercalciuric children (daily calcium excretion >4 mg/kg/day). Results: Mean UCa/Osm ratio was significantly lower in the first (1) group than the second (2) group (0.11±0.07 vs 0.31±0.14 mg/L/mOsm/kg, p<0.05); But there was no difference between 2a and 2b subgroups. The correlations of both UCa/Osm and UCa/Cr ratios with 24-hour calcium excretion were poor (r=0.27 for both). Conclusion: UCa/Osm ratio correlated with spot UCa/Cr ratio. But its superiority on UCa/Cr ratio in the diagnosis of hypercalciuria could not be shown. Interestingly, values of 24-hour calcium excretion as a definite diagnosis test of hypercalciuria; did not correlate mathematically with those ratios of hypercalciuric or non-hypercalciuric children. Using UCa/Osm ratio as a screening test would not separate hypercalciuric children.

Background: Microalbuminuria is a biomarker of renal damage. The presence of microalbuminuria in patients with a solitary kidney has been described, but the pathophysiology leading to its occurrence is poorly understood. It is postulated that microalbuminuria is the early result of hyperfiltration. Methods: We concomitantly measured inulin clearance, filtration fraction (FF) and microalbuminuria in children with a single kidney. Correlation between the occurrence of microalbuminuria and a high filtration fraction was done. Microalbuminuria was defined as an albumin/creatinine ratio (ACR) >3 g/mol for boys and girls. Normal filtration fraction was defined as <26%, and normal inulin clearance as >90 ml/min x 1.73 m 2 . During the same study, we also measured microalbuminuria in children with severe grade III to V vesico-ureteral reflux (VUR). Results: 27 children with a single kidney were evaluated. 18 patients (67%) had a normal FF, and only one (6%) in that group had an abnormal ACR. 9 patients (33%) had elevated FF, and 5(56%) had an abnormal ACR. The presence of an abnormal ACR was highly correlated with an abnormal FF (p=0.008). The mean GFR between the groups with normal or abnormal microalbuminuria did not differ significantly (94±31 ml/min x 1.73 m 2 vs. 83±16 ml/min x 1.73 m 2 , respectively). There was no significant association between microalbuminuria and a high FF in patients with severe reflux (p=0.3). Discussion: We found the presence of microalbuminuria to be significantly associated with an elevated FF in children with a single kidney. This finding goes in line with the pathophysiology of a reduced nephron mass, leading to hyperfiltration, and ultimately to glomerular sclerosis. The benefit of renin-angiotensin-aldosterone blockade in these patients remains to be proven. Chyluria is the excretion of chyle from the urinary tract and indicates the presence of an abnormal communication between intestinal lymphatics and the urinary tract. It can be of parasitic or nonparasitic etiology. Southern Brazil is not an endemic region for filariasis. AIM: report a case of a 14-yrs Caucasian adolescent girl referred to our out-patient clinic. History: 3 yrs before, she started to pass milky urine with white clots. No edema. Normal blood pressure. She was investigated in another hospital and underwent a renal biopsy, that was normal. A diagnosis of nephrotic syndrome was made. She was treated initially with steroids and after changed to cyclosporin, lisinopril and simvastatin. Conclusion: chyluria, although a rare conditione specially in children and adolescent in nonendemic areas, should beconsidered in the differential diagnosis of nephrotic syndrome. Macroscopic examination of the urine, that is milky and cloudy, is simple and very helpful. Also, triglycerides are found only in the urine of patients with chyluria. These simple tests will avoid unnecessary treatment, which is not without side effects.

Low-density lipoprotein apheresis (LDL-A) has been tried in the treatment of patients with steroidimmunosupression resistant nephrotic syndrome (NS) due to focal segmental glomerulosclerosis (FSGS). We would like to report a child case study of FSGS with NS and renal insufficiency due to mitochondrial abnormality treated by LDL-A and to clarify the therapeutic effects of this treatment. A 12-year-old boy was referred to our hospital with complaints of heavy proteinuria and edema. A routine examination revealed proteinuria of 7.0 g/day, serum albumin (Alb) of 1.9 g/dL and creatinine clearance (Ccr) of 58.5 mL/min. Renal biopsy specimen showed FSGS and perceptive deaf nass was recognized, necessitating a hearing aid. The A3243G point mutation in mitochondrial gene was detected by using genomic DNA isolated from peripheral blood leukocytes and by the molecular analysis using an allele-specific polymerase chain reaction (PCR). Oral prednisone (2 mg/kg/day for eight weeks), intravenous methyl-prednisone pulse therapy (1.0 g/day,three times a week on the consecutive days for three weeks) and oral cyclophosphamide (75 mg/day for eight weeks) were not effective to reduce proteinuria. A protocol of LDL-A was designed for treatment twice-a-week for four weeks and then once-a-week for six weeks. Following treatment by LDL-A, serum total cholesterol and LDL were markedly changed form 271 to 118 mg/dL and from 198 to 91 mg/dL, respectively. A small but significant increase in Alb from 1.9 to 2.9 g/dL and a remarkable decrease in proteinuria from 7.0 to 1.4 g/day were also successfully obtained. Conversely, no marked changes in Ccr were detected. The results of the present study indicate that a rapid decrease in proteinuria and an excellent increase in Alb by LDL-A provide a possible therapy for drug-resistant NS due to FSGS with mitochondrial abnormality. 

Glomerular filtration rate (GFR) can be estimated in children by various formulas based on body height and serum creatinine (S Cr ) measurements such as the Schwartz formula (eGFR Sch =kxBH/S Cr ). We evaluate the performance of eGFR Sch in estimating GFR in a pediatric cohort when compared to 125 I-iothalamate clearance (iGFR), used as the reference standard for measuring GFR. Between 1996 and 2006, we obtained 265 iGFR and eGFR Sch on 171 subjects. For subjects who had more than one iGFR, the first measurement was used for analysis. Mean age was 13±6 (range 1-20, 56% age=13), 55% male. Mean S Cr was 1.2 mg/dl (median 0.8), mean iGFR 76±38 ml/min/1.73 m 2 and mean eGFR Sch 116±59 ml/min/1.73 m 2 . Figure 1 shows a scatter plot of the data with a line representing perfect agreement. Figure 2 shows a residual plot comparing the difference between estimated and measured GFR to eGFR Sch . Pearson R correlation between the two variables was 0.87 (ln scale). Accuracy of eGFR Sch within 20% and 50% was 20% and 50%, respectively. The median difference between iGFR and eGFR Sch was 40.1 ml/min/1.73 m 2 (median % difference 50%). For iGFR >60, 30-59, 15-29 and <15 ml/min/1.73 m 2 , eGFR Sch overestimated GFR by 46%, 66%, 48% and 44%, respectively. However, the median difference between iGFR and eGFR Sch for the same groups was 39, 18, 8 and 4 ml/min/1.73 m 2 , respectively. In conclusion, agreement between eGFR Sch and iGFR is poor. eGFR Sch overestimates iGFR at all levels of GFR, but bias of eGFR Sch vs. iGFR increases progressively with higher GFR levels. In clinical instances when an accurate estimation of GFR is critical for patient management, the use of eGFR Sch should be reconsidered. Until a more applicable estimation equation is developed, isotope measurement of GFR remains the ideal method to determine GFR in this population. Background: Immunosuppressive therapies other than corticosteroids, potentially associated with serious adverse effects, are urgently required for children with frequently relapsing nephrotic syndrome (FRNS). This study evaluated the efficacy and safety of long-term treatment with a moderate dose of cyclosporine (CyA) in children with FRNS. Methods: In this prospective, open-label multicenter trial, patients, from 2 to 16 years old, were randomly divided into two groups. For the first 6 months, both groups received CyA (Sandimmune) in a dose that maintained the whole-blood trough level between 80 to 100 ng/ml. During the next 18 months, the dose of CyA was adjusted to maintain a trough level between 60 and 80 ng/ml in Group A, while Group B received a fixed dose of 2.5 mg/kg per day of CyA. The primary end point was the rate of sustained remission. Results: At 24 months, the rate of sustained remission was 52% in Group A (n=24 patients), as compared with only 15% in Group B (n=20) (p=0.006). The hazard ratio for relapse was 0.36 (95% CI, 0.17 to 0.77) in Group A as compared with Group B (hazard ratio=1.0). At 24 months, the rate of progression (to FRNS)-free survival was 78% in Group A and 56% in Group B (p=0.12). Mild arteriolar hyalinosis of the kidney was found in 4 (19.0%) of 21 patients in Group A and 1 (5.6%) of 18 in Group B; no patient had striped interstitial fibrosis or tubular atrophy. Conclusion: CyA given for 2 years in a dose producing a trough level between 80 and 100 ng/ml for the first 6 months, followed by a trough level between 60 and 80 ng/ml for the next 18 months is an effective and relatively safe treatment for children with FRNS. With this regimen, about 50% of patients are expected to remain relapse-free during 2 years of treatment, without the most critical adverse effect of CyA, i.e., interstitial changes of the kidney. Renal stone disease has been regarded as an uncommon problem in children especially in the first year of life. We evaluated clinical findings and metabolic examination of 49 children with urinary tract stone presenting in the first year of life. There were 25 boys (51%) and 24 girls (49%), the mean age of admittance was 6,04±3,15 months. The average follow-up period was 30,91±24,65 months. Urolithiasis was diagnosed during evaluation for UTI and incidentally. Positive family history for urolithiasis was reported in 22 (44,8%) patients. In 28/38 (73,7%) patients urinary metabolic examination was not normal (Table 1 ). In 48 of 49 patients (98%), stones were located in kidneys which was bilateral in 26 (52%) patients and one patient had passing stone which had never seen in ultrasonographic examination. Stones were examined in 3 subgroups. In 39 (80%) patients stones were measured 5 mm or smaller (Group 1), in 9 patients (18%) they were between 5-9,9 mm (Group 2) and in only 1 patient the stone (cystin) was larger than 10 mm (Group 3). Stones measuring 5 mm and larger were found highly associated (in 7 of 10 children, 70%) with abnormal ultrasonographic findings mainly hydronephrosis. In Group 1, stones disappeared spontaneously in 12/23 (52%) patients. Urinary tract infections (UTI) were present in 28 (57%) patients. One fourth of cases had associated genitourinary tract abnormalities mainly vesicoureteral reflux in 9 (18%) patients. We conclude that the presenting symptoms of urolithiasis in the first year of life show a wide spectrum so that high index of suspicion is important for early detection. Stones measuring 5 mm and smaller may have great chance to disappear. We also emphasize the importance of screening for UTI in patients with urolithiasis under 1 year of age. Background: Long term complications of glycogen storage diseases (GSDs) include delayed puberty, hepatic adenoma and renal disease. In the present study we aimed to detect renal involvement in children with glycogen storage disease and to determine the most accurate laboratory test to be the gold standard for early detection of this renal dysfunction. Methods: Twenty-seven children known to have GSD were included in this study. Fifteen healthy age-and sex-matched children were also included as controls. Routine urine analysis, urinary β2 microglobulin and microalbumin were done for all patients and controls. Renal function tests, serum electrolytes, alkaline phosphatase, urinary calcium, blood and urine pH, urinary and plasma aminogram, in addition to calculation of glomerular filtration rate (GFR), bone X-ray to detect rachitic manifestations and abdominal ultrasound to measure renal size were done for all patients. Results: Twenty-one patients had one or more renal abnormality. The most common was increased urinary β2 microglobulin (15/21) followed by abnormal GFR whether low or high (8/21) and microalbuminuria (6/21). Sonographically there was nephrocalcinosis in one case and renal stone in another one. The AUROC curve for β2 microglobulin was 0.86, (P=0.01) and 0.7 for urinary microalbumin/creatinine ratio (P=0.15). The best cutoff level to predict renal abnormality for urinary β2 microglobulin was 0.22 mg/l with 70% sensitivity and 100% specificity and the best cutoff value for urinary microalbumin/creatinine ratio was 4.5 with 86% sensitivity and 50% specificity.

In conclusion: Renal abnormalities are common in patients with GSD. Urinary β2 microglobulin can be considered the gold standard for early detection of renal dysfunction in these patients. The aim of this study was to investigate the role of neutrophil activation, protein oxidation and ceruloplasmin in the pathogenesis of HSP, which has been not investigated previously. Serum activities of myeloperoxidase (MPO) and arylesterase (ARYL) and levels of free thiol, ceruloplasmin (CLP) and total oxidant status (TOS) were measured in 29 children with HSP (16 boys, 13 girls; mean age 9.3±2.7 years) at the onset of the disease and during remission in comparison with 30 matched healthy subjects. Patients at active stage had significantly higher MPO activity (391±277 vs. 155±154 U/L, P<0.001), higher CLP (832±120 vs. 682±114 mg/dL, P<0.001) and TOS values (20.7±11.8 vs. 7.5±2.8 μmol H 2 O 2 /L, P<0.001) than controls. Patients had significantly lower ARYL activity (158000±39000 vs. 187000±46000 U/L, P<0.001) and lower free thiol levels (234±48 vs. 279±26 μmol/L, P<0.001) than controls. There were 17 patients with GIS involvement, 14 with joint and 13 with renal involvement. No significant differences were found in the oxidant stress markers between patients with or without organ involvement (P>0.05).

Significantly positive correlations were found between TOS and MPO (r=0.437, P=0.018), and TOS and CLP (r=0.409, P=0.028) at the disease onset; while a negative correlation was found between MPO and thiol (r=-0.597, P=0.001) during remission. In conclusion, protein oxidation and neutrophil activation may play important roles in the pathogenesis of HSP. Gastrointestinal system, joint and/or renal involvements were not together with different magnitude of oxidant stress. Further studies are required to identify oxidizing substances and to develop therapeutic strategies to reduce oxidant stress in HSP. 1, 21) . If the first remission occurred after 8 days, the median time to relapse after discontinuation of steroid therapy was significantly lower than in children with shorter remission time (0.5 vs 3.0 months; p<0,0001). In conclusion children who fail to achieve a prompt remission after a first episode of NS are more likely to have FRNS or SDNS. These retrospective data provide the rationale for individualizing the initial steroid treatment of MCNS according to the time to obtain a remission. A prospective study is needed to validate this approach. The aim of this study was to determine the influence of osmolality of the first morning urine (OFMU) to efficacy of the desmopressin therapy in enuretic (PNE) children and to compare the values of OFMU in enuretic and non-enuretic children. Methods: We investigated OFMU in group of 50 children with PNE and in group of 36 control non-enuretic children. PNE group was divided into subgroup I (OFMU <600 mOsm/kg H 2 O) and subgroup II (OFMU >600 mOsm/kg H 2 O). Additionally, we measured OFMU 1 months after the initiation of desmopressin therapy and recorded the number of wet nights. Regarding the number of wet nights we divided PNE group to 3 subgroups: subgroup A (<5 wet nights/month), subgroup B (5-10 wet nights/month), and subgroup C (>10 wet nights/month). Results: The statistically significant difference between control group and PNE group regarding OFMU was not found (p=0.612). All 10 children from subgroup I had <5 wet nights/month during desmopressin therapy. 14 children from subgroup II had <5 wet nights/month, and 26 had >5 wet nights/month during desmopressin therapy. The difference between those two groups was statistically significant (X 2 =13.3, p=0.0003). In children from subgroup A the difference between OFMU-s during and before treatment was 413 mOsm/kg H 2 O, in children from subgroup B it was 261 mOsm/kg H 2 O and in children from subgroup C it was 117,5 mOsm/kg H 2 O. There was the statistically significant difference among those subgroups. Conclusion: Children with PNE had usually similar OFMU like non-enuretic children. Low OFMU is a good prognostic factor for desmopressin therapy of PNE, especially in patients whose OFMU is <600 mOsm/kg H 2 O. Children with bigger difference of OFMU before and during therapy had better response to desmopressin therapy. We can conclude that OFMU can help in choosing the appropriate therapy for PNE in children.

YH. Ng 1 , KL. Chan 2 1 KK Women's and Children's Hospital, Pediatric Nephrology, Singapore, Singapore 2 Singapore General Hospital, Neonatology, Singapore, Singapore Aim: To evaluate the clinical course and outcome of primary vesicoureteric reflux (VUR) in patients with antenatal hydronephrosis in a neonatal unit. Method: A prospective observational study of neonates with antenatal hydronephrosis born between January 1991 and December 2000 in the neonatal unit of Singapore General Hospital. Neonates with significant hydronephrosis postnatally underwent micturating cystourethrography (MCU). Records were reviewed with regards to the clinical course and outcome of primary VUR. Results: Of 280 neonates with antenatal hydronephrosis, 139 (49%) had significant hydronephrosis postnatally and underwent MCU. 12.9% (18/139) were diagnosed with primary VUR at median age of 7 weeks. There were more male (n=11) than female infants with primary VUR. 10 (56%) infants had bilateral VUR. 18% (n=5) of the renal refluxing units (RRU) had low grade VUR and 82% had high grade VUR with the majority (57%) being Grade III VUR. Repeat MCU for 15 RRU at 2 years showed that 60% (n=9) had spontaneous resolution of VUR, 27% had improved VUR grade and 13% had similar VUR grades as before. 2 infants develop VUR in the contralateral kidney which was previously normal. 14 infants (23 RRU) underwent DMSA with renal scarring noted in 4 infants. All 4 infants were noted to have renal scarring without a history of urinary tract infection (UTI). Interestingly, 2 male siblings were found to have Grade III VUR with renal scarring with subsequent spontaneous resolution. None of the study subjects underwent surgery. Median age of follow-up was 3.8 years (range 0.3-12.5 years). Conclusion: Unlike neonates with VUR detected after UTI, infants with primary VUR were predominantly male, had higher grade of VUR with spontaneous resolution in the majority. Early diagnosis of primary VUR may provide the opportunity for reduced incidence of reflux nephropathy.

T. Neveus 1 , G. Läckgren 1 , J. Wahlberg 2 , N. Wahlin 1 1 Uppsala University Children's Hospital, Uppsala, Sweden 2 Uppsala University Hospital, Department of Transplantation Surgery, Uppsala, Sweden Objectives and methods: Loin pain hematuria syndrome is a rare entity consisting of recurrent macroscopic hematuria with debilitating loin pain. It has only been described in adults, etiology is unclear and treatment is controversial but the therapy with best recorded success is to remove the kidney and reposition it in the pelvis. Our objective was to show that the condition exists in childhood as well. Results: AJ, a previously healthy 9-year-old girl, was admitted because of recurring cystitis-like symptoms with microscopic hematuria but without bacteriuria. Ultrasound and urography were normal. The episodes continued during the following years with increasing hematuria, now macroscopic, and increasing loin pain that was somewhat exercise-dependent. A renal CT scan was normal, as was cystoscopy, urography and ultrasound, but during cystoureteroscopy dilated vessels were noted in the mucosa of the right renal pelvis. Antegrade pyelography, high resolution renal CT angiography, invasive renal angiography, MAG3 renogram were all normal, GFR 111. Nephrological evaluation, including kidney biopsy and coagulation tests were also normal and during cystoscopy blood could be seen emerging from the right ureteral orifice. By this time the patient was 15 years old and was dependent on opioids in order to be able to go to school. After long discussions with the nephrologist, urologists, pain specialist and transplantation surgeon, the family opted for autotransplantation as a last resort. This was performed january 2006 and the girl became almost momentarily pain-free. Nowadays she does not need any analgesics, but after prolonged exercise (like several days of horseback riding) she may experience slight pain in the left loin and/or hematuria. Conclusions: Idiopathic loin pain hematuria syndrome exists in childhood and may possibly be treated with renal autotransplantation.

J. Van der Deure, A. Ockhuijsen, M. Sondaar Deventer Ziekenhuis, 1st Department of Pediatrics, Deventer, the Netherlands Objective: Enuresis is a common pediatric problem. Psychosocial factors (PSF) influence the results of enuresis treatment in children. Aim: To determine the short and long term effects of PSF on enuresis treatment in a general pediatric population. Methods: We reviewed the data of our enuresis patients treated from 2002-2004. Relevant contributing PSF were categorized. Initial follow-up was at 3 months after training. A written questionnaire was sent 2 years after training. Treatment success was defined as >90% improvement in dry nights. Results: 211 pts were included. In 65 pts (30.8%) contributing PSF were recognised. Categorized problems: Family related n=28 (43%), Behavioural problems n=28 (43%), Motivation/support n=22 (33.8%), Learning disabilities n=21 (32.3%). Overall success rate was 75.3% at 3 months and 65.3% at 2 yrs (overall resp quest 63.7%, PSF 60.6%, 1 PSF 51%, >1 PSF 73%). Success rate in the PSF group was 49.2% (1 PSF 61.5%, >1 PSF 30.7%) at 3 months and 43.2% (1 PSF 45%, >1 PSF 42%) at 2 yrs. Statistics: Success rate in the group with PSF is significantly lower as compared to no PSF at 3 months (p<0.001 (chi-square), OR 9.3, 95% CI 4.2-20.2) and at 2 yrs (p=0.0017 (chi-square), OR 3.7, 95% CI 1.6-8.1) Success rate at 3 months is significantly lower in pts with >1 PSF, compared with 1 PSF. (p=0.011 (chi square), OR 4.6, 95% CI 1. 5-13.9) . No significance could be demonstrated at 2 yrs (p=0.85, chi-square) but this may be due to the variety in response rates.

T. Papalia, R. Greco, R. Bonofiglio Hospital Annunziata, Nephrology, Cosenza, Italy Actually a new litholitic therapy includes the Phytotherapy agents as Phyllantus niruri (Pn), a plant used for years in Brazil to treat urinary stones. In this work we estimate the effect of Pn intake (Uristone 2 gr/die) in 15 children (9 M/6 F, 9±5 years old) with urolithiasis. The Pn has been administered for short term (from 1 to 3 months) in 13 children wih CaOx urinary stones and for 6 months in 2 with struvite stones. Besides all children treated with dietary intervention: high fluid intake, sodium restriction, normal calcium intake and a diet low in animal protein. Urinary and plasma analysis, body weight, MAP, pH, creatinine clearance, urinary excretion of Mg and citrate were determined at baseline, 1 month and at the end of the study. The patients were studied by renal ultrasonography at baseline, 1, 3, 6 months. Nobody of them had been undergone extracorporal shock wave lithotripsy. There were no differences in the mean values of urinary and plasma parameters before and after Pn intake, except for a significant reduction in the mean urinary calcium in 8 hypercalciuric pts (6±1,3 vs 3,5±1 mg/kg/die). In this follow-up N°10 patients showed a faster stone clearance after a regular intake of Pn and the others showed a smaller stone diameter. Previous reports showed Pn has a potent inhibitory effect on CaOx crystal adhesion and/or endocytosis by renal tubular cells and inhibitory effect on crystal growth, which might be related to the higher incorporation of GAGs into the calculi. Our results suggest Pn appears to represent a nontoxic and a low cost alternative for the prevention and treatment of stone disease, especially in the children. Further studies are necessary to validate these preliminary findings. D. Weitzel, C. Schäfer, K. Hohenfellner, U. Pfeffer, M. Neukirch German Clinic for Diagnostic, Pediatrics, Wiesbaden, Germany Objective: Does sonographic quantification of the renal parenchyma allow estimation of isotopic renal function? Method: Sonographic kidney images of 88 patients (age 1 to 195 months; mean 47) were measured retrospectively. In all images of both kidneys taken from dorsal the volume on the base of length, width and depth was calculated. The parenchymal area (PA) in the longitudinal and cross section was calculated by planimetry. The distribution of renal function via MAG3 was compared with sonographic values as volume and PA of each kidney in relation to whole kidney volume and PA respectively. Patients with reduced global kidney function and time space of more than 3 months between isotopic study and sonography were excluded. Results: Interrater variability regarding planimetry of PA in longitudinal section (from dorsal taken images) was as good as measurement of kidney length (correlation coefficient (k)=0,968-0,977 and 0,97-0,99 respectively). All sonographic parameters correlated significantly with the isotopic parameters of renal function. The latter correlated best with the PA in longitudinal section (from dorsal taken images) k 0,939. The combination with planimetry in cross section did not improve correlation (k 0,94). Difference of the proportional PA of the left kidneys (in correlation to whole kidney PA) in comparison to isotopic proportional renal function lead to mean difference of -0,3% with a standard deviation 6,7%. If only kidneys with split function of 45-55% the mean difference of proportional PA was -0,6% and the standard deviation 3,6%. Conclusion: The distribution of total PA of both kidneys correlates significantly with the distribution of renal function (left and right) in isotopic studies. If sonographic planimetry might change the indication for isotopic studies in respect of renal function needs to be proofed in prospective studies. Background: Childhood incontinence is a common important urologic problem. Especially daytime incontinence is often neglected by the parents until it turns out to be a significant clinical problem. The aim of this study was to evaluate the clinical characteristics of the patients with incontinence that were followed in our nephrology clinic. Study design: Patients were followed between the dates of 01.01. 2004-31.12.2006 and they were admitted solely due to incontinence or with concomitant urinary tract infections were enrolled. Results: The study comprised 99 patients (38 M, 61 F; mean age 9.78±3.06 years). Fourty-two patients had only nocturnal enuresis (NE) (29 primary, 13 secondary). Twelve patients had daytime incontinence (DI) (4 primary, 8 secondary) and 45 had both NE and DI (25 primary, 13 secondary and 7 both primary NE and secondary DI). All, except two (neurogenic bladder), had functional incontinence. Twelve patients had additional fecal incontinence and 8 had constipation. Sixty-two percent of the patients had one or recurrent urinary tract infections (UTI) in their past history, 16% had accompanying vesicoureteral reflux and 4% had urinary stones. Ultrasound revealed unilateral or bilateral dilatation in 20% and other anomalies in 5% of the patients. Nineteen patients had abnormal dimercaptosuccinic acid scintigraphy findings. Timed voiding schedule and double voiding were recommended to all patients with daytime incontinence, 43% of the patients received anticholinergic treatment and 50% received antimicrobial prophylaxis. Discussion: Overall, approximately 2/3 of our patients had associated UTI and 1/5 had abnormal DMSA findings. Therefore every patient with UTI should be questioned about urinary incontinence and be treated carefully if present. The aim of the study was to determine early parameters of ultrasound and DMSA scanning diagnostics of reflux nephropathy (RN) in children. We examined 150 children with RN and vesicoureteric reflux (VUR). All children were comparable on gender and age. All patients underwent color Doppler ultrasound (CDUS), X-ray and DMSA scan. They were divided into two groups: 1) children with unilateral RN A according to classification of Smellie J. et all, 1975 (n=75) ; 2) children with VUR without renal damage (n=75). We established that data of CDUS (diastolic velocities (Vd) 5,94±0,99 mm/sec, systolic velocities (Vs) 22,3±5,74 mm/sec, resistive indices (Ri) 0,63±0,06, pulsatility indices (Pi) 0,76±0,19), DMSA scanning (time of the maximal accumulation 11,8±0,91 sec, maximal activity 189,3±20,4 sob/sec, mean velocities of accumulation 29,1±1,9 mm/sec, the contribution to the common accumulation 45,3±3,5%) are characteristic for patients with RN A. Data of CDUS (Vd 10,7±1,68 mm/sec, Vs 23,9±1,7 mm/sec, Ri 0,63±0,02, Pi 1,08±0,24), DMSA scanning (time of the maximal accumulation 7,5±0,86 sec, maximal activity 81,5±11,9 sob/sec, mean velocities of accumulation 7,72±1,07 mm/sec, the contribution to the common accumulation 34,27±3,03%) are characteristic for patients with VUR without renal scars. The ranges of CDUS and DMSA scanning were significantly different between children from comparing groups (p<0,05). Our result suggest that data of CDUS (Vd, Vs, Ri, Pi), DMSA scanning (time of the maximal accumulation, maximal activity, mean velocities of accumulation, the contribution to the common accumulation) can be used to early diagnostics of scarring in children with VUR. 

The purpose of this study was to determine normal reference values for urinary uric acid/creatinine ratios in healthy Turkish children. In this study, random urine specimens from 1306 children (662 boys, 644 girls) aged 1 month to 15 years were analyzed for uric acid and creatinine, and urinary uric acid/creatinine ratios were determined from each sample. Uric acid/creatinine ratios were the highest in children aged 1-6 months and showed a significant decrease with age (p<0.05). Uric acid/creatinine ratios were not significantly different between the sexes except 12-15 years. Girls between 12-15 years had higher urinary uric acid/creatinine ratios when compared with boys (p<0.05). There was no correlation between urinary uric acid/creatinine ratios and protein intake. Our results show that urinary uric acid/creatinine ratio changes with age. When assessing the urinary uric acid/creatinine ratio, a child's age should be considered. We provided normal reference values of urinary uric acid/creatinine ratio for using in our region. The aim of the study was to investigate microbiological marker of activity of UTI. E. coli and S. aureus P 209 were isolated from urine of 180 children with UTI. The children were divided into 4 groups: 1. with pyelonephritis in the acute period (n=45); 2. with pyelonephritis in the period of remission (n=45); 3. with cystitis in the acute period (n=45); 4. with cystitis in the period of remission (n=45) 20 healthy children consists the group of control. Definition of bactericidal activity of urine (BAU) was carried out by our original method. The essence of the method consisted in measuring of the optical density (OD) of the bacteria after their contact with urine (experience) and isotonic solution of NaCl (control) after 30 minutes of endurance in meat peptone mediums with 37 C during 3-5 hours. BAU was calculated under the formula: BAU (%)=(ODc-ODe)/ODc*100%, (ODc -control group, ODe -experience group). We established that the level of BAU did not correlate with urine pH (r=0,2), osmolality (r=0,1), lysozymuria (r=0,2), lysinuria (r=-0,2). We established that the low level of BAU was marked in children of control group (10-40%). The patients in active period of UTI had high level of BAU (>70%). The parameters of BAU didn't depend from the level of UTI (pyelonephritis or cystitis). The level of BAU reduced in the period of remission of UTI. We established that the level of BAU correlated with bacteriuria (r=0,8), leucocyturia (r=0,5). The level of BAU didn't depend from the degree of urine dissemination (r=-0,3). So, the level of BAU is correlated with laboratory parameters of UTI and can be used as new additional microbiological marker of diagnostics of activity of UTI.

The Evolution of the Alport Syndrome in Brazilian Children Vesicoureteric reflux (VUR) is common in children with urinary tract infections (UTI). If VUR coexisting with UTI there is a high risk of progression to end-stage renal disease (ESRD). The correct diagnosis is important. We observed 136 children (104 girls and 32 boys) aged 1 mo to 12 yrs at the time they have been diagnosed as having VUR. The follow-up period was 1 mo up to 11 yrs after the diagnosis. All 22 children with VUR grade 5 have been operated. After antireflux operation incidence of UTI dramatically decreased even this cannot prevent progressive kidney damage in some patients. Children with less severe VUR have been put on prophylaxis. Controlled MCU was performed usually after 1 year later. If VUR disappeared medication have been stopped. VUR grade 2-4 had a tendency of resolution under conservative treatment in 25.5% of the patients.

In 16 children associated urinary tract malformations were found: duplicated system, dysplastic kidney, kidney agenesia, dystopic kidney, urethral stenosis and bladder outlet obstruction. In 2 patients nonfunctioning kidney have been found. Dysfunctional voiding was common finding. Blood pressure and physical development have been controlled. Kidney size, function and scar formation have been followed by DMSA scan. We observed kidney growth at 6 mos intervals. During the follow-up period 3 infants have had reversible renal insufficiency. One patient with bilateral VUR grade 5 went into renal failure at the age of 9 yrs. Conclusions: VUR is still one of the most common leading causes to ESRD in childhood. Even the existing controversy concerning treatment modalities it is obvious that low grade VUR does not need operative treatment. It is indicated in high grade VUR to prevent repeated and severe UTI but it cannot preserve progression of the disease because of high incidence of coexisting kidney dysplasia. Results: From forty children with nephrolitiasis, 28 (70%) were boys and 12 (30%) were girls. The mean age was 80.5±57.5 months. The youngest age was 4 months old. The most common clinical presentation was abdominal discomfort 22 (55%), followed by UTI 21 (52%), microscopic hematuria 13 (32.5%), macroscopic hematuria 12 (30%), spontaneous urinary calculi 9 (22%), flank pain 8 (20%). Nine of 40 children were presenting with chronic renal failure (CRF). Statistical analysis showed that age had correlation with the present of CRF in children with nephrolitiasis (P=0.007).

The clinical presentations of nephrolitiasis were varied. Abdominal discomfort and UTI were the major signs and symptoms. There was correlation that age may influence the present of CRF in children with nephrolitiasis.

Objective: Renal involvement is one of the most frequent and serious manifestations of SLE. We analyzed the treatment and renal outcome of patients with lupus nephritis. Methods: Seventy-seven identified patients were retrospectively analyzed from Jan. 1996 to Dec. 2005 . The outcome was divided as complete remission (24-hour proteinuria <0.5g, plasma creatinine level normal and SLEDAI <5), partial remission (abnormal renal damage index improved >50%, 24-hour proteinuria >0.5g, SLEDAI <10) and no response, respectively. Results: Fifty-four patients were biopsy proven LN (70%). Fifty-seven patients followed up more than 6 month. All the eleven patients with class I or II achieved remission, using prednisolone together with either HCQ, or tripterygium or MMF or cyclophophamide (CTX). In forty-three patients with class III or IV or V, they were given prednisolone together with MMF or CTX. We found that remission was in 18 cases, part remission 17 cases and no response in 8 cases. Associations between methylenetetrahydrafolate reductase (MTHFR) C677T polymorphisms and several vascular diseases have been reported. This is a clinical study designed to investigate the possible effects of (MTHFR) C677T polymorphisms on the developement of Henoch-Schönlein purpura (HSP), renal involvement, and clinical course. Fourty-one patients with HSP (25 M/16 F) mean age (7,8±2,9 years) were included in the study. Eighteen of the patients had renal involvement. The control group consisted of 50 healthy children. Blood samples were obtained for MTHFR C677T transition, homocysteine, folic acid and Vitamine B12 in the patients and controls. The genotype frequencies (CC/CT/TT) of MTHFR in the HSP group were 0,56/0,39/0,12 and 0,58/0,38/0,04 in the control group, respectively (NS). The genotype frequencies (CC/CT/TT) were 0,39/0,39/0,22 in the patients without renal involvement and 0,78/0,22/0,00 in those with renal involvement, respectively (NS). Homocysteine levels were 10,6±6,8 in the HSP patients and 12,9±4,5 μmol/l in controls (NS). Vitamine B12 levels were 320,6±157,5 pg/ml in the HSP patients and 302,6±209,6 pg/ml in the control group (NS). Folic acid levels were 5,7±3,0 in the HSP and 4,0±1,6 ng/ml in the control group (p<0,002). No significant relationship was present with the MTHFR genotype and plasma homocysteine, folic acid and vitamine B12 levels.

No association with MTHFR gene polymorphism and homocysteine plasma levels could be detected in patients with HSP and HSP nephritis. Although MTHFR gene polymorphisms have been found to be associated with several vascular diseases, the results of this study indicate that other mechanisms should be operative in the developement of HSP and HSP nephritis.

We report the symptoms, signs and laboratory values at onset and during 6 month-follow-up of HSP in a prospective study of 220 children (99 girls, 121 boys) with mean age of 7.1 years (1.6-16.7 y). The first sign of HSP was purpura in 152 (70%), oedema or other joint symptoms in 121 (55%), abdominal pain in 49 (22%) and melena in 3 (1%) patients. Petechiae appeared on the average 5 days after the first symptoms (1-22 d) if purpura was not the first sign (n=67). 78% of the cases were diagnosed between September and March. The mean delay from the first symptoms to the diagnosis was 7 days (0-65d Our results based on an unselected and prospective patient material demonstrate that renal symptoms in HSP children develop early, are common and should be followed up at least 6 months. The kidney is a metabolically active organ, so any alteration in kidney function might affect nutrient utilization. Objective: Analyze the nitrogen balance (NB) as a marker for adequate food consumption in children with chronic renal insufficiency (CRI). Material and methods: 60 patients (12 boys, 48 girls) diagnosed and managed in the Nephrology and Nutrition Departments. They were placed in two groups depending on age: Group A: 20 patients aged 5±2.5 years, follow-up 4±1.1 years, glomerular filtration rate (GFR) estimated by Cr-EDTA: 38±20 ml/min/1.73 m 2 ; Group B: 40 patients aged 12.5±3 years, follow-up 10.9±3.5 years, GFR estimated by Cr-EDTA: 37±17 ml/min/1.73 m 2 Results: Group A had a worse weight and height evolution: Weight: -0.95±0.15 SD in group A vs 0.15±2 SD in group B; height -1.29±0.29 SD vs -0.34±0.23 SD (respectively). Group A showed a significant increase in TNF blood levels (p<0.03) that was inversely related with weight and height. BN was significantly greater in group A (1.59±1.93 gr/day) than in group B (-2.6±4gr/day) (p<0.01) and this was related with higher calorie (p<0.003) and protein (p<0.004) intakes. There was no difference in alimentary nutritional breakdown. NB improved significantly over the follow-up (p<0.01). There was no relation between NB and GFR. There was a significant increase in triglyceride levels and significantly lower blood urea levels in group A (p<0.04). We conclude that nitrogen balance depends on protein and calorie consumption and is independent of the severity of renal affectation. We present a case of a 6 months old boy, who was delivered to our intensive care unit because of high fever, acute renal failure and dilatation of the urinary tract. His hemoculture and urinary culture were positive for E. coli and a severe urosepsis was diagnosed. His urethral catheterization was unsuccessful, so a suprapubic puncture was performed to relieve the urinary system and provide sufficient urinary flow. After the urinary sepsis was cured with adequate board spectrum antibiotics, a voiding cystourethrography (VCUG) was performed to reveal the suspected anatomical abnormality, vesicoureteral reflux (VUR) respectively. Meanwhile a continuously growing nodular tumor of the penis was observed. The VCUG showed the signs of urethral stenosis, but posterior urethral valve and VUR was excluded. The Doppler ultrasound found a solid vascularised tumor, 2x2.5 cm in its diameter. During the surgical operation the tumor couldn't been totally removed, as it was infiltrating the surrounding tissues and the urethra. The histopathological examination of the biopsy specimen confirmed a juvenile xanthogranuloma (JXG). This is an uncommon, benign, non-Langerhans cell histiocytosis, primarily seen in infancy as a solitary cutaneous lesion, predominantly in males. Systemic form of the disease is rarely seen. Usually it resolves spontaneously without any further treatment, but the differentiation from a malignant neoplasm is essential. According to the authors' search, this is the 2nd reported case in the literature and the first pediatric report of the JXG of the penis. 

Urine Examination Using X-ray Diffractometry Background and Goal: X-ray powder diffraction analysis is widely used in chemistry and pharmacology and for other industrial purposes. In medical science it is used for analyzing kidney stones and investigating retained crystals in tissue sections. In the Department of Mineralogy and Petrology we investigated urine samples, at first diagnostically to detect urinary amino acids, glucose and compounds and, secondly, to detect calcium oxalate hydrate, which can be employed for early detection of renal tubular injury when no significant differences in renal function values exist. Materials and Methods: After sedimentation and dehydration, authors investigated more than 100 urine samples of children using X-ray diffractometry.

Results: 12 of them were glucosuric due to diabetes mellitus; in these cases glucose could be detected in each of their urine samples. In 5 cases different amino acids due to aminoacidopathy were detected. The urine samples of 8 children -kidney stone problems in history -were examined, in one case struvit, in the other cases Ca oxalate crystals were identified. Also, 30 samples of 10 children were examined, 24 hours after at least 2 hours long anesthesia, Ca oxalate hydrate appeared in their urine referring to renal tubular injury due to inhalational anesthetic agents. In 10 cases urine samples of children treated in the Intensive Care Unit were analyzed, in 50% Ca oxalate crystals could be detected. In 40 cases healthy children's urine were investigated, as control ones.

Conclusion: X-ray diffractometry, as a highly sensitive method can be used efficiently in clinical measurements. Further investigations are needed in order to determine its place in clinical trials. Authors emphasize the importance of collaboration of different sciences, as well.

Drug Intake in the Background of Sudden Death? Microalbuminuria was significantly more in patients more than 10 years of age as compared to younger patients on bivariate analysis (P=0.001). On logistic regression analysis, though microalbuminuria was more in patients more than 10 years of age, it was not statistically significant. The association between microalbuminuria and urinary specific gravity levels of <1.010 was statistically significant (P=0.001), similar results were seen on logistic regression analysis. There was no correlation between microalbuminuria and hospitalizations, crises, previous blood transfusions, hemoglobin electrophoresis and serum creatinine levels.

Conclusion: Identification of risk factors for microalbuminuria may allow earlier intervention to prevent renal complications in patients with SSD. In developing countries at primary health care level urinary specific gravity should be done routinely in patients with SSD to identify cases at risk of microalbuminuria.

M. Bak, E. Serdaroglu, Y. Bicilioglu

Aim: The aim of the present randomized-controlled study was to compare desmopressin (DP), alarm and combined treatments in nocturnal enuresis.

The study included 101 children (67 boys and 34 girls) with nocturnal enuresis. The mean age was 10.7±2.4 years (ranged 5-16 years) and the mean wet-nights was 14.9±6.1 day per month before treatment. The patients were followed for one month before treatment and randomized to DP (33 patients), alarm (34 patients) and combined (34 patients) treatment groups. The DP group was received 40 μg orally one-hour before sleep and alarm group was used Wet-Stop bedwetting alarm device after education of parents. The patients were followed 6 months in treatment period and 2 months after discontinuation of treatments. Results: Wet-nights per months was significantly reduced between before treatment and last month of treatment in DP (14.5±5.7 to 4.8±6.5, p<0.001), alarm (14.1±5.9 to 2.9±4.1, p<0.001) and combined treatment (16.2±6.9 to 1.9±2.5, p<0.001) groups. Treatment success (>50% decreasing in wet-nights) and complete response (100% dry) rates was 79%, 91%, 97% and 30%, 27%, 35% in DP, alarm and combined treatment groups respectively. The more rapidly decreasing in wetnights was observed between DP used and only alarm treatment group but this effect disappeared after 3 months. Relapse rates was 67%, 11% and 22% in DP, alarm and combined treatment groups respectively between successfully treated patients (p=0.002). Conclusion: Alarm treatment is the best intervention with low relapse rates and no potential adverse effect in nocturnal enuresis. DP group has higher relpse rate but adding to DP may achieve more rapid decreasing in wet nights especially in patients and parents expecting rapid result. Aim: It is often difficult to collect urine from infants. Use of specifically designed urine collection pads gives reliable results for routine biochemistry tests in adult urine. Their use for routine and metabolic tests in paediatric urine has not been investigated. The aim of this study was to evaluate whether the pads give reliable results for routine and metabolic biochemistry tests in paediatric urine. Methods: Urine collected by bag or clean-catch from infants <2y without metabolic disorders was divided into two aliquots, one of which was added to a collection pad, incubated for 15min at 37°C, then recovered by aspiration. Routine and metabolic analyses were performed on pad/non-pad aliquots. Additionally, selected metabolic analyses were performed on pad/non-pad urine from patients with diagnosed inborn errors and urine spiked to simulate metabolic disorders. For quantitative analyses, pad/non-pad results were compared using Bland-Altman bias plots, Passing and Bablok regression and paired t-tests. Results: Routine tests (urea, electrolytes, creatinine, osmolality, calcium: creatinine, phosphate: creatinine, magnesium: creatinine, urate: creatinine, n=32) showed close concordance with no clinically significant pad/non-pad differences. In infants without metabolic disorders, aminoacids (n=10), organic acids (n=12) and mucopolysaccharides (n=8); and in patients with metabolic disorders -phenylketonuria (n=1), mucopolysaccharidoses II (n=2) and III (n=1), inborn errors of organic acid metabolism (n=6) and cystinuria (n=3), all showed excellent pad/non-pad concordance. Sugar chromatography in urine spiked with glucose/galactose/fructose showed identical staining intensity in pad/non-pad samples. Conclusion: Urine collection pads give reliable results for a wide range of routine and metabolic tests in paediatric urine.

A Post-translational modification of arginine residues in proteins and subsequent proteolysis result in release of symmetric dimethylarginine (SDMA). SDMA is considered an end product of metabolism, excreted primarily by the kidney. Several previous studies have reported a significant relationship between glomerular filtration rate (GFR) and plasma SDMA. To determine the potential value of SDMA in the assessment of GFR in children we have measured SDMA in samples taken during routine measurement of glomerular filtration rate (GFR) using plasma clearance of Inutest. 257 patients (144 male) requiring routine GFR measurement were studied. Median (range) age 11.8y (1.6-20.2) , height (Ht) 145cm (82-188), and surface area 1.3 m 2 (0.5-2.6). GFR was measured using the plasma clearance of Inutest, and plasma SDMA and creatinine (pCr) by liquid chromatography stable isotope dilution electrospray mass spectrometry-mass spectrometry method. Estimated GFR (eGFR) was calculated from the formula 31 x Ht (cm)/pCr (μmol/l). Median GFR was 80 ml/min/1.73 m 2 (6-217), plasma SDMA 0.530 μmol/l (0.266-4.460 ), pCr 54.5 μmol/l (12.7-777), and eGFR 82 ml/min/1.73 m 2 (7-212). As expected both plasma SDMA and pCr increased with a decline in GFR. Compared to GFR the correlation with 1/SDMA, r=0.83 (P<0.001) was better than for 1/creatinine, r=0.75 and similar to that for eGFR, r=0.86. Comparing SDMA with Inutest GFR for detection of GFR <90 ml/min/1.73 m 2 the area under the ROC curve was 0.87 (P<0.001). The equivalent areas for pCr and eGFR were 0.84 and 0.89, respectively. In conclusion plasma SDMA is an endogenous marker of GFR in children and is superior to pCr because it appears to be independent of body size. Since the calculation of eGFR requires accurate measurement of height, plasma SDMA may provide a practical alternative for assessment of GFR in children.

Thrombotic microangiopathy (TMA) consists of thrombocytopenia, microangiopathic hemolysis, and thrombi in the microvasculature of vital organs. Broad categories of causes of TMA include infectious (verotoxin-induced HUS), hematologic (TTP), complement based (atypical HUS), immune-mediated (SLE, anti-phospholipid antibody syndrome), and drug-induced (cyclosporine). Thorough investigation is required to detremine the underlying etiology in order to provide specific therapy and information about prognosis.

A 14 year girl presented with short stature and was found to have hypertension, proteinuria, renal failure (creatinine 350 umol/l), and anemia (Hgb 72 g/l). Platelets were normal. She also had spondylometaphyseal dysplasia, scoliosis, lymphopenia, mild pulmonary hypertension and aortic stenosis. On pulmonary function testing, her DLCO was decreased. Chest CT demonstrated small micronodules. A ventilation-perfusion scan was normal. Renal biopsy showed features of TMA. She was treated with dialysis and underwent renal transplantation one year later. There has been no disease recurrence 6 months post-transplant. Genetic and immunologic workups were negative, including anti-cardiolipin antibodies. A thrombophilia workup was negative apart from a heterozygous mutation in MTHFR. C3 levels were mildly reduced. Anti-neutrophil antibodies were negative. Complement system studies, including Factor H, and SMARCAL1 analysis for Schimke immuno-osseous dysplasia are underway.

Although the descriptive diagnosis of TMA can be applied here, the underlying pathophysiologic diagnosis has still to be defined. It is of particular importance that further efforts be made to identify the etiology given the potential risk of disease recurrence in the renal graft. Background: Long term outcome of renal functions after liver transplantation (LT) in WD is not studied yet. Aim: The aim of this study was to determine the long term outcome of renal functions in children receiving LT for WD. Patients and Methods: Renal functions were examined in 9 (F/M: 2/7) liver transplanted patients for WD before and long after LT and compared with renal functions of 9 patients (F/M: 5/4) with LT for a hepatic disease other than WD. The mean age of subjects was 12.1±3.2 years in the patients group and 9.8±4.1 years in the controls. The mean duration of follow-up was at least 2 years. Glomerular and tubular functions were assessed using the conventional equations for measured creatinine clearance (GFR), tubular phosphate reabsorption (TPR), daily protein and calcium excretion in both groups. Results: Mean GFR before LT was 81.7±32 mL/min/1.73 m 2 in the study group and 146.3±37.6 mL/min/1.73 m 2 in the controls (p=0.007). The mean TPR before LT was found to be 67.9%±18.2% in the study group and 88%±9.6% in the controls (p=0.03). Daily protein excretion rate before LT was found to be high in both groups, as well as urinary calcium excretion. An increase in GFR was observed in the study group after LT (p> 0.05), while it was slightly decreased in the controls (p>0.05). TPR increased significantly in the study group after LT (84.8%±9.5%) (p=0.04) and although it was found to be significantly lower in the study group than the controls before LT, in the long term follow-up the difference between the groups was disappeared (p=0.59).

Conclusion: Tubular dysfunction is frequent in patients with WD. Liver transplantation for hepatic failure secondary to WD is a lifesaving procedure. It corrects the underlying hepatic defect as well as renal defects and leads to long-term survival. Rather conflicting results are available regarding the neurocognitive development of children with CKD, due to small sample sizes, cross-sectional study designs, differing methodological approaches and historical trends in patient selection for renal replacement therapy. We prospectively examined in a standardized, multi-center effort 59 children with CKD aged 0.8-15 years. Children were treated either conservatively (n=30, GFR <25 ml/min/1.73 m 2 ) or by dialysis (HD: n=7, PD: n=22). A sub-sample of 18 children underwent repeated testing after 12 -14 months. Bayley and Snijders-Oomen developmental tests were performed and the measured values normalized to standard deviation scores (SDS). General cognitive development averaged at -1.02 (±1.48) SDS. 42% of the patients scored <-1.5 SDS, i.e. below the 10 th percentile of the normal population. No significant differences were observed between pre-dialysis (-0.87+1.57) and dialyzed patients (-1.16+1.40). Impaired neurocognitive function was marked in infants (-1.63+1.31 SDS), whereas school children showed a distribution similar to healthy children (0.43+1.42 SDS, p<0.005). The global neurocognitive SDS remained unchanged in the longitudinal sample (t 1 =-0.97±1.57; t 2 =-0.91±1.71). In summary, our preliminary results demonstrate a high prevalence of neurocognitive impairment in infants with CKD. We assume that this finding reflects the improved survival of children with complex disorders affecting not only the kidney but also brain development. The poor performance of this age group highlights the importance of close neurocognitive follow-up and early developmental interventions. Objectives of study: To make a diagnosis of a girl with kidney subcapsular hydrops, abnormal urinanalysis and hypertension. Methods: Physical examination and laboratory investigations were analyzed. Results: A 5 years old girl was admitted because of kidney subcapsular hydrops, proteinuria without edema, and hypertension (130/94 mmHg) for 50 days. No trauma or familial hypertension history were provided. No hydrops was found before the age of 1 year. Urinary RBCs were 5-7/Hp and protein was 77 mg/kg/24 hr. The serum albumin was normal. Ultrasound examination revealed normal sized kidneys, increased echogenicity in both kidneys, and subcapsular hydrops on the upper pole of the right kidney connected with an old renal fissure. UCG and fundus examinations were normal. GFR of the right kidney was slightly decreased as compared to the left (65 ml/min vs. 67 ml/min, by DTPA scan). By puncture of hydrops, yellow clear fluid was drained, the analysis showed similar composition to that of original urine, so subcapsular urinoma was diagnosed. Urine collection from two kidneys separately was performed by cystoscopy; nonselective proteinuria of 1+ was found in urine from the right and 2+ from the left kidney. Analysis revealed urea 36.8 mmol/l, potassium 6.92 mmol/l, creatinine 0.42 mmol/l in the right kidney urine compared to urea 77.2 mmol/l, potassium 11.19 mmol/l, and creatinine 1.29 mmol/l in the left, which suggested that the right kidney function was compromised. According to proteinuria from both kidneys with microscopic hematuria, without edema and hypoalbuminemia, glomerulonephritis was diagnosed.

The girl was diagnosed with glomerulonephritis and subcapsular urinoma. It was a rare case because of their co-incidence. Reasons for the hypertension, if caused by the glomerulonephritis or the pressure by subcapsular urinoma, as well as reasons for subcapsular urinoma need to be clarified during the follow-up. The aim of this study was to detect factors that could interfere with the results of DES treatment. Methods: Fifty-six patients 5.9 to 15.2 years old with DES without improvement by previous therapies were randomly distributed into two voiding training programs: group 1 (G1): 26 patients submitted to 24 Kegel exercises training sessions for three months; group 2 (G2): 30 patients submitted to 16 biofeedback sessions over a two month period. Both groups adhered to a voiding and drinking schedule, received adequate toilet posture instructions and were reinforced through the maintenance of voiding diaries. Clinical evaluation was carried out before each programs initiation and 1, 6, and 12 months after end of the program. All patients were submitted to renal and dynamic ultrasound before and 6 months after each program's conclusion. The following variables were analyzed: gender, age at diagnosis, treatment group type, vesico-ureteric reflux, constipation, urinary tract infection, asymptomatic bacteriuria, bladder wall thickening and post void residual (PVR) urine. The logistic regression model was applied to identify independent variables associated with response to treatment. Results: Urinary continence was improved after completion of either training program. Success in diurnal urinary incontinence varied from 72.7 to 80% in G1 and from 65.2 to 89.4% in G2. Success in nocturnal urinary incontinence varied from 66.7 to 84.2% in G1 and from 65.4 to 86.9% in G2.

In multivariate analysis three variables remained independently associated with bad response to treatment: constipation with soiling, bladder wall thickening and PVR urine (p<0.05). Conclusion: Studies using multivariate regression analysis to identify predictors of response to behavioral therapy are important for the development of selection criteria for prescribing these therapies to children. We report the case of a four-year-old child born to consanguineous parents, who presented first at two months of age with respiratory failure. During the admission he developed panyctopenia, hypertension and nephrotic range proteinuria. The metabolic workup revealed methylmalonic academia and aciduria along with homosystinuria; highly suggestive of cobalamin deficiency. The renal biopsy showed chronic thrombotic microangiopathy (TMA). The muscle biopsy showed the presence of nemaline rods on electron microscopy. Cobalamin C deficiency was confirmed by genetic analysis as the patient was homozygous for the mutation C547/548. At the age of one, he was noted to be visually inattentive and developmentally delayed. On ophthalmology examination there was evidence of bilateral maculopathy and dysfunction of rods and cons on electroretinogram. He subsequently went on to develop bilateral bovine maculopathy. Since his initial presentation he has been maintained on hydroxycobalamin, betaine and folate; with no further relapse of proteinuria or panyctopenia. However, despite adequate doses of hydroxycobalamin, the maculopathy progressed. To our knowledge, this is the first report of a child with both TMA and bovine maculopathy. The aim of the study was to assess the rate of vesicoureteral reflux (VUR) in patients with Lower Urinary Tract Dysfunction (LUTD) of nonneurogenic origin. Dysfunctional voiding may result in lower urinary tract symptoms in children and is commonly associated with urinary tract infections and VUR. We investigated 111 patients with voiding dysfunction during last three years: 31 boys and 80 girls, a mean age of 8.2 years, with a mean follow-up of 19 months, all with normal renal function. Mean pre and post treatment symptom scores were 23.6 and 7.6 respectively. VUR was detected in 21% of the children with unstable bladders and 17.5% of the children with stable bladders as detected by video urodynamic investigation, 22% of the children with urinary tract infection (UTI) on admission, and 18% of the children with no history of UTI on admission. The co-existence of VUR in our group with voiding dysfunction was 19.8% (22 patients). All patients with VUR had low grade reflux (grades I-III) and 3 of them bilateral, the remaining 19 unilateral. Renal US was performed in 55 patients and revealed hydronephrosis in 13 patients, while the remainder showed no abnormalities. VUR was found to be present in 30% of the children with abnormal US findings, while only 2% of the children with normal US findings were affected. Furthermore, the patients that had spontaneous resolution of reflux showed a markedly greater improvement in symptom scores. A significant portion of patients with LUTD (19.8%) have low grade VUR. In detection of VUR in patients with LUTD, hydronephrosis is a good indicator of the presence of reflux, while UTIs and urodynamic findings were not found to be significant indicators. The overall spontaneous resolution rates of VUR in patients with LUTD and stable bladder following treatment was found to be 22.7% and 14.2%, respectively. 200-250g) were grouped: Group 1 (n: 5) was the sham group. Group 2, 3 and 4 (n: 7 for each) received 50 mg/kg twice daily PTX intraperitoneally (i.p.), 100 mg/kg/day GEN i.p. and both PTX and GEN at the same dosages for 8 consecutive days, respectively. The rats were weighed at the beginning and than weekly during the study. After the last dose 24-hour urines were collected. Then, rats were sacrificed and blood samples were obtained from the abdominal aorta. BUN, serum creatinine (Scr), creatinine clearance (CCr), renal superoxide dysmutase (SOD), catalase (Cat) and thiobarbituric acid reactive substances (TBARS) levels were determined. All the parameters were compared between the groups. Results: Body weights were not different between the groups either at the beginning or during the study. BUN levels were significantly higher in group 3 than the other groups (p<0.01). Scr and CCr levels were similar between the Groups 3 and 4, but the levels were higher than those of Groups 1 and 2 (p<0.01). SOD and TBARS levels were similar between all groups. The levels of tubular cell apoptosis and caspase-3 expression were significantly higher in Group 3 than the other groups (p<0.05). Conclusion: We may conclude that PTX administration significantly reduced the apoptosis in GENtoxicity, but we could not demonstrate any evidence of PTX-related reduced oxidative stress. The lack of evidence for the widespread use of antimuscarinics and holding exercises in MNE prompted us to design a randomized controlled trial comparing interventions in four groups of children with MNE: placebo (A) or oxybutynin chloride (B) in combination with a daily regimen of standardized fluid intake and holding exercises or as monotherapy (C) and (D). A fifth group, to be treated with alarm only, was planned as control. Randomization was stratified for participating hospital, sex, age, Tanner stage, family history of MNE, previous treatment, and bladder capacity class, being the largest from either the maximum voided volume (MVV) from a 48 h frequency volume chart or the volume after 4 baseline holding exercises (HEV). After 12 weeks intervention with holding exercise (A and B) , HEV had increased, both with oxybutynin (208±84 (SD) ml to 311±121 (SD) ml, p<0.001) and placebo (216±82 (SD) ml to 259±90 (SD) ml, p<0.05). Without holding exercises, only oxybutynin (D) increased HEV (223±79 (SD) ml to 274±111 (SD) ml (p<0.05). MVV increased also in groups A and B (holding exercises), not C and D. Cure rate (less than 1 wet night in the last for 4 weeks) was low: A 1/29, B 3/30, C 0/30 and D 4/30. Control group with alarm had 22/30 cure. Cure was not related to HEV, MVV or delta HEV and MVV. This questions the relevance of increasing bladder capacity in MNE. Background: Sickle cell disease (SCD) is an inherited disorder of beta-globulin synthesis of haemoglobin, resulting in a tendency for haemoglobin polymerisation and consequent vasoocclusion, tissue hypoxia, and ensuing organ damage. The kidney is a particularly sensitive to hypoxia and renal failure is a major cause of morbidity and mortality in SCD. Children with SCD commonly hyperfiltrate, the glomerular filtration rate (GFR) then typically falls back towards normal in adulthood. Routine estimation of GFR in children is primarily derived from the height and plasma creatinine (pCr) measurements using k a constant dependent on the creatinine analytical method. This formula has reduced accuracy in children with a GFR >80ml/min/1.73 m 2 . It has never been validated in hyperfiltration or children with SCD. Recently, new GFR markers have been proposed including symmetrical dimethylarginine (SDMA) that may be independent of body size.

In this pilot study we tested the hypothesis that estimated GFR and/or SDMA allow a reliable estimation of GFR in SCD. Methods: 13 HBSS patients, age range 10-20yrs (mean age 15yrs) attending the Evelina Children's Hospital were studied. The patients were on regular blood transfusions for stroke management and undertook a formal GFR measurement using plasma clearance of Inutest. The plasma samples were also used for the measurement of pCr and SDMA by stable isotope dilution mass spectrometry. eGFR was calculated using k=35. Results: Inutest GFR ranged from 70-175 ml/min/1.73 m 2 . There was significant inverse correlation between SDMA and Inutest GFR (P<0.01)). There was no significant correlation between either pCr or eGFR and Inutest GFR.

Conclusions: This early data suggests that SDMA might prove valuable in monitoring GFR in children with SCD. Introduction: The aim of this study was to identify the risk factors for renal scarring in children with lower urinary tract dysfunction (LUTD) by using data available at the time of patient admission to the Interdisciplinary Management Program of LUTD at Hospital das Clínicas. Material and methods: Medical records of 120 patients were assessed retrospectively concerning gender, presence of vesicoureteric reflux (VUR), bladder capacity, detrusor overactivity, residual urine, urinary tract infection (UTI), asymptomatic bacteriuria, constipation, detrusor-sphincteruncodination (DSU), high detrusor pressure at maximal cystometric capacity, low compliance, thickness and trabeculation of the bladder wall. Renal scarring was diagnosed by DMSA scan. Statistical analysis was performed by univariate and multivariate analysis. A P value <0.05, 95% confidence interval was considered significant. Results: Renal scarring was detected in 38 patients (31%). Abnormal bladder capacity, detrusor overactivity, residual urine, asymptomatic bacteriuria, constipation, DSU, high detrusor pressure and low compliance were not associated with renal sccaring. VUR, UTI, decreased bladder capacity, urinary residue, trabeculated and thick bladder wall were associated with scarring at univariate analysis. Multivariate analysis showed VUR (p<0.0001) and female gender (p=0.05) as independent risk factors for renal scarring. Thickness of the bladder wall was a marginal risk factor (p=0.07). Conclusion: Urodynamic parameters didn´t predict renal damage in this study. UTI was not a risk factor for renal scarring; however, it was associated with VUR (p=0.03). Although VUR was the main risk factor in our analysis, renal scarring was probably due to multifatorial causes as VUR was associated with ITU. Results: Comparison of test A and B demonstrates that a mild fluid load 1 h before the administration of dDAVP nasal spray (2 puffs) results in 3 major significant differences.1). Maximal concentrating capacity (CC) is reached later than 1h after administration (p<0.05). In 8/46% CC at sleeping time is <70% of max, thereby resulting in a persistent NP in the first hour of the night. 2) Uosmol is significantly (23%) lower in the overnight collection (U4), correlating with a higher diuresis-rate (16%)3). The duration of the DDAVP effect is shorter leading to an increase in diuresis-rate and to a decrease in the U osmolality in 24/46 children in the urine-collection between 4-7h in the morning. This proves that in up to 50% of the patients the dDAVP-effect does not cover the full night.

Conclusion: Test B demonstrate sthat fluid intake prior to the dDAVP-administration influences significantly the antidiuretic effect of dDAVP (onset, maximum and duration). This might explain the partial response, suggestive for insufficient Pd (and PK) effect of the spray. Test A proves that fluid restriction 1 h before DDAVP administration, significantly reduces the nocturnal diuresisvolume.

M. Schmidts, C. Schnakenburg, K. Häffner, C. Jacobi, K. Schwab, M. Pohl University Hospital, Center for Pediatrics and Adolescent Medicine, Freiburg, Germany Background: Enteropathic hemolytic uremic syndrome (D+HUS) is responsible for 90% of all HUS cases. In addition to the nephrological and neurological complications, pancreatic damage resulting in diabetes mellitus is also possible and appears to be associated with more severe cases and elevated mortality. Case report: A 3-year-old girl suffering from D+HUS with severe colitis, acute renal failure, dyskinesia, dysarthria and agitation provoked by Shiga-like toxin positive EHEC infection in July, 2006. The severe affection was characterized by partial thalamic infarction, prolonged leukocytosis (max. 51 G/l) and the necessity of 4 weeks of dialysis. 6 days after the disease onset, hyperglycemia (max. 530 mg/dl glucose) was noted. C-peptide was found to be low indicating reduced insulin secretion. 6 months after HUS the patient continues to be insulin dependent. Clinically apparent exocrine pancreatic insufficiency has resolved spontaneously. GFR had recovered to 28 ml/h/1,73 m 2 , but then kidney function deteriorated and dialysis had to be resumed after 5 months. Kidney histology at this time showed severe nephron loss compatible with chronic changes after HUS and ruled out other unrelated kidney disease.

Conclusion: In addition to the kidney damage, chronic pancreatic damage can occur in HUS. Therefore blood glucose levels should be monitored in all HUS patients. It is tempting to speculate that patients after childhood HUS might be at risk for diabetes mellitus later in life.

Objective: Childhood nephrotic syndrome (NS) is characterised by a relapsing course resulting in significant corticosteroid burden or prescription of cytotoxic immunosupressive therapy. This randomised controlled study was carried out over 3 years at a single centre in Sri Lanka to compare the efficacy and safety in children with steroid dependant NS treated with intravenous cyclophosphamide or intravenous vincristine therapy. Methods: Thirty-nine sequential children with steroid dependant NS with evidence of steroid toxicity were randomly allocated to receive either intravenous cyclophosphamide (500 mg/m 2 monthly for 6 months) or vincristine (1.5 mg/m 2 weekly 4 doses followed by 4 doses monthly). Both groups received an identical tapering regimen of oral prednisolone for 6 months. All children were reviewed on monthly basis for one year focusing on recurrence of proteinuria and side effects of therapy. Finding of +++ proteinuria for 3 consecutive days was diagnostic of relapse.

Results: There were 18 (11M: 7F) children in the cyclophosphamide group (mean age 6.4 years) and 21 (15M: 6F) in the vincristine group (mean age 7.2 years). During one year of follow-up 6/18 (33%) in the cyclophosphamide group suffered a relapse while 13/21 (62%) suffered a relapse in the vincristine group. p=0.03 (comparison of 2 proportions using Standard Error. CI 0.105 to 0.49).

No serious adverse effects were encountered in either group. Conclusion: In steroid dependant NS, intravenous cyclophosphamide therapy is superior to intravenous vincristine therapy in maintaining sustained remission. We present the clinical and biochemical features of a patient with antenatal Bartter syndrome who was found to have a novel ROMK mutation. The patient presented antenatally with severe polyhydramnios. Polyuria, hyponatraemia and hyperkalaemia were evident soon after birth. She had marked hypercalciuria and developed medullary nephrocalcinosis in early infancy. Failure to thrive was evident from 12 months. Hypokalaemia was a late feature, developing gradually from 18 months. Serum chloride levels were consistently 95-100 mmol/L whilst urinary chloride levels were consistently <30 mmol/L, only reaching higher levels after treatment was commenced. Alkalosis was not present and the patient did demonstrate some response to furosemide implying some functional capability of Na-K-2Cl. Renin and aldosterone levels were persistently elevated. Treatment with indomethacin, NaCl and KCl produced a good clinical response. Mutational analysis revealed compound heterozygous mutations in KCNJ1, the gene encoding ROMK. Both mutations, M357T and L359R are in the terminus of the protein thought to have a role in channel gating. Similarities and differences from the classically described presenting features of antenatal Bartter syndrome highlight the clinical heterogeneity in this condition. This relates to the different identified KCNJ1 mutations which are likely to affect ROMK function in different ways. The M357T mutation has been described, but past electrophysiological studies in Sf9 cells transfected with the M357T mutant have not identified any differences in K + conductivity from wild type ROMK. Given that the mutation appears to be clinically relevant in this case, further functional studies are indicated. L359R is to our knowledge a novel mutation. Expression of these mutations in oocytes is now planned to enable evaluation their effects on channel function and regulation. A 10-year-old boy was admitted because of nephrotic syndrome. Renal biopsy, performed after 4 weeks of prednisone (60 mg/m 2 od) + 3 methylprednisolone pulses (15 mg/kg each), showed focal segmental glomerulosclerosis. Prednisone was tapered (to 30 mg/m 2 od) and enalapril was introduced, without any significant improvement. Two weeks later, the patient had transient hypoperfusive acute renal failure which required ACEI discontinuation. Due to the persistence of proteinuria, Cyclosporine was started (5mg/kg/day). Proteinuria gradually decreased and ceased within the subsequent two weeks. In the meantime the boy had started to complain of low-grade fever without other symptoms and with normal physical examination. Laboratory tests only showed leucocytosis (WBC 22 x 10 3 /mL) and increased C-reactive protein (65 mg/l). A chest X-ray revealed an upper mediastinal enlargement and a total body CT scan confirmed the presence of several enlarged mediastinal lymph nodes, whose biopsy led to the diagnosis of Hodgkin disease (HD) nodular sclerosis subtype, CD30+; stage was IIA. Cyclosporine and the residual steroid treatment were discontinued and the patient was given six cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), followed by radiation therapy. Presently, 18 months after stopping chemotherapy, both HD and nephrotic syndrome are still in remission. Once again, this case points out both that FSG can be secondary to a lymphoproliferative disease and that chemotherapy for HD might have been effective to keep FSGS in long-lasting remission. Several treatment methods including increased fluid intake and dietary modification, medical therapies such as potassium citrate and use of Extracorporeal ShockWave Lithotripsy (ESWL) and finally surgery methods are used for treatment of urolithiasis. The aim of this study was to evaluate the etiological and clinical characteristics and level of response to medical therapy with polycitra in children with urolithiasis. One hundred thirty-four patients had urolithiasis of which 109 cases followed thetreatment instructions and fulfilled the inclusion criteria for this study. Struvite stone were excluded from the study. All other patients who had an initial ultrasonography showing stone inurinary tract were treated with polycitra-k (potassium citrate 220 grams, citric acid 66.8 grams in 1 liter of distilled water) irrespective of the cause of the stone. At the end, complete resolution or passage or a decrease in the size of stone in later sonography was defined as response to treatment. Hypercalciuria and hyperuricosuria were found to be etiological factor in 25% and 19% of patients respectively. The stone analysis was found that 50% of them were Ca-oxalate. Stone disease was more common between the age of 1-5 years. The most common complaint was hematuria (20%). ESWL was performed in 42% of patients who did not respond to polycitra and had surgically active stones. Calcium-oxalate stones were the most frequent stone which responded to polycitra. The response rate in girls and boys was equal and in different age groups the response rate was almost equal. Methods: MMCs were expanded in culture and immunocytochemistry was used to characterize the cells. After gentamicin-induced ATN, fluorescently-labeled cells were transplanted and traced in kidney tissues by fluorescence microscopy. Kidney pathology was studied by hematoxylin-eosin staining, apoptosis was examined by the TUNEL assay, and Ki-67 and Bcl-2 expression were examined by immunohistochemistry and reverse transcription-polymerase chain reaction, respectively. Results: (1) MMCs (RIMM-18 cells) were successfully expanded in culture. The phenotype of the cultured cells were vimentin-positive and kreatin-negative by immunocytochemistry. (2) In the MMCS-treated group: the mortality rate decreased; renal function clearly improved; damage to the cell-treated kidneys was reduced and histopathologic lesion scores were lower; proliferation of renal tubular epithelial cells was improved; the apoptosis of renal tubular epithelial cells was reeuced; and the expression of Bc1-2 mRNA and protein was upregulated.

The subcapsular transplantation of MMCs could ameliorate renal function and repair kidney injury.

ATN is the most common reason for ARF, and there is still an absence of effective therapies. This study was done to observe the effect of mobilizing bone marrow cells with stem cell stimulating factor (SCF) and GM-CSF on recovery from gentamicin-induced acute tubular necrosis (ATN) in rats. ATN was included in male Sprague-Dawley rats with five daily high dose intraperitoneal injections of gentamicin. Subcutaneous injections of SCF and GM-CSF were administered simultaneously and these cytokines was observed at day 2, 5, 10, 17, 24 and 31. Leukocyte numbers, percent venous blood CD34+ cells, mortality rate, and concentration of the urine proteins, urine NAG, BUN, SCr, and CCr, histopathogic lesion scores were determined. Twelve hours after bone marrow ablation (BMA) by lethal X-ray radiation, gentamicin-induced SPF AtN rats were given five daily injections of SCF and GM-CSF. BUN, SCr, and histopathogic lesion scores were evaluated at day 2, 5 and 10. The effects and mechanism of SCF and GM-CSF on ATN was observed. The number of leukocytes and the CD34+ cell percentage increased significantly in ATN rats between 2 and 10 days after SCF and GM-CSF injection. In addition, mortality rates dropped, the peak value of renal function increased, renal function were rapid ameliorated and histopathologic lesions were reduced. There was no significant effect on ATN rats after BMA. This study demonstrates that SCF and GM-CSF effectively mobilized bone marrow stem cells in ATN rats. rapidly improving renal function and decreasing mortality rate. These results suggest that bone marrow stem cell mobilization may be an effective therapy for ATN. Key words: acute tubular necrosis, bone marrow stem cells, stem cell factor, granulocytemacrophage colony stimulating factor, irradiation. Objective of the study: The response to recombinant human erythropoietin (rHuEPO), 50 unit/kg twice weekly was studied prospectively in 35 children and adolescents with end stage renal failure who were either transfusion dependent or had hematocrits (HCT) <25%. Methods: rHuEPO was given to 22 haemodialysis (HD) patients and 13 patients on conservative treatment, with mean age (10.84±4.08) years, 25 males and 10 females with mean HCT (26.75±4.70). Blood pressure, haematocrit, iron-indices, serum potassium, calcium, phosphorus, alkaline phosphatase, urea nitrogen and intact parathyroid hormone (iPTH) were monitored serially. Results: Serum aluminum was measured randomly in 6 patients, results were normal ranging from 12-22 ug/l. When serum ferritin was <100ng/ml during therapy, they received iron supplementation. According to the response, patients were divided into 2 groups, the non-responders group with HCT<27, mean age (9.97±3.55) years, 13 males and 6 females with mean iPTH (669.9±461.77 pg/ml) and group of responders with HCT >27 with mean age (11.66±4.32 years),12 males and 4 females with mean iPTH ( Increase of fatty acids such as nonesterified fatty acid (NEFA) and triglyceride (TG) with oxidative stress and production of cytokine/chemokine occured during cisplatin (CP) toxicity. Statin (3hydroxy-3-mthylglutaryl coenzyme A reductase inhibitors) have been postulated to have pleiotrophic effects. We examined whether statin, pravastatin, would ameliorate renal damage induced by CP. Male Wistar rats (weight 180-200 g) fed standard chow were divided into 3 groups: Control-rats received tap water alone for 19 days; CP treatment-rats that received CP (10 mg/kg, i.v.) on the 14 th day of the study; CP+Pravastatin treatment-rats that received pravastatin (6 mg/kg/day) in their drinking water for 19 days and CP injection as indicated in the preceeding group. Blood and urine samples were collected and the kidney were removed 5 days after CP treatment. Urinary excretions of protein and 8-hydroxy-deoxyguanosine (8-OHdG), serum levels of creatinine and fatty acids were measured. Histology was evaluated by light microscopy with immunohistochemistry for pentosidine, N-carboxymethyllysine (CML), and heme oxygenase (HO)-1. Expression of HO-1 mRNA in the kidney was also measured. Pravastatin decreased urinary excretions of protein and 8-OHdG and ameliorated renal function diminishing areas of tubular damage and positive staining of pentosidine and CML compared with those of CP treatment alone. However, positive staining area and mRNA expression of HO-1 were not significantly changed by pravastatin treatment. Although pravastatin did not influence serum levels of total and low-density lipoprotein cholesterol, serum TG level decreased and was equivalent to that of control group. These findings suggest that pravastatin treatment partially protects against CP-induced nephrotoxicity in rats, through its antioxidant as well as lipid-lowering effect.

N. Bresolin, V. Fernandes, F. Carvalho, J. Goes, L. Araujo, M. Simon, G. Gamborgi, M. Zanin Hospital Infantil Joana de Gusmo, Nephrology Pediatric Department, Florianópolis, Brazil Objectives: the objective is a report case of acute renal failure (ARF) in a child contact with Lonomia obliqua caterpillar in Southern Brazil. The accidents with Lonomia oblique has increased in South of Brazil in recent years. This increase can be related with reduction of caterpillar natural predators and deflorestation. The venom of Lonomia caterpillar provokes hemorrhagic syndrome resembling disseminated intravascular coagulation (DIC) and hemolytic anemia. ARF could be an important complication of hemoglobinuria that has been recently described in adults.

Methods: a case report. Results: the present is a first case described of ARF in a child after contact with Lonomia obliqua caterpillar.

Conclusions: the ARF can occur in any age, however, the contributing factor to the development of ARF remains obscure. There are 3 mechanisms pointed out: fibrin deposition in glomerular microcirculation, ischemia in hemorrhagc shock with hypotension and venom direct action. The present article related a case of Lonomia obliqua accident in a child who revealed coagulation disorder, hemolytic anemia, ARF and always, she was hemodynamic stable. The treatment included antilonom serum, urine alkalinization, hyperhydration and peritoneal dialysis for four days. She was treated and followed per 1 year when she recovered her normal renal function.

Introduction: secondary hyperparathyroidism develops in chronic kidney disease as a consequence of impaired phosphate, calcium and vitamin D homeostasis. The treatment includes phosphate binders and vitamin D analogues, but sometimes ineffective. We report two cases of refractory secondary hyperparathyroidism treated successfully with cinacalcet. Case 1: a 21-month-old boy with end stage renal disease (ESRD) due to posterior urethral valve started on peritoneal dialysis at 12 months of age. He developed secondary hyperparathyroidism with serum parathyroid hormone (PTH) level reaching 585 pg/ml. Serum calcium had been in the range of 6.7 to 9.6mg/dL and serum phosphorus in the range of 1.7 to 10.7 mg/dL. Despite treatment with phosphate binders and vitamin D analogues, PTH levels kept increasing to 897 pg/ml. X-ray showed the cupping and fraying of the distal ends of radius and ulna. We started cinacalcet 10 mg daily and increased the dosage up to 30 mg daily. Eight months later, PTH level decreased to 154 pg/ml and bone changes resolved. Case 2: a 12-year-old boy with ESRD due to primary hyperoxaluria started on peritoneal dialysis at 10 years of age. He developed secondary hyperparathyroidism with serum PTH level of 641 pg/ml. Serum calcium had been in the range of 7.9 to 9.7 mg/dL and serum phosphorus in the range of 5.9 to 11.1 mg/dL. Despite treatment with phosphate binders and vitamin D analogues, PTH level kept increasing to 1457 pg/ml. X-ray showed the distal radius and ulnar fracture of left arm and right femur fracture. We started cinacalcet 30 mg daily. Five months later, PTH levels decreased to 151 pg/ml. Conclusion: cinacalcet is effective in the secondary hyperparathyroidism resistant to phosphate binders and vitamin D analogues in children with chronic renal failure. Rota virus (R) is a common pathogen as the cause of gastroenteritis in childhood. We experienced some cases with R infection who had the renal failure induced by uroammoniac calculi as well as dehydration. We examined the clinical feature and laboratory findings of the cases with viral acute gastroenteritis in R and non-Rota virus (NR) groups for 2005-2006. With rapid diagnosis test, we checked the patients that needed the hospitarization medical treatment from newborn to five-years old. In the 42 cases of R group and 23 cases of NR group, we campared the clinical findings, blood chemistry test and urinalysis of R groups in acute and convalescent a tage with those of NR group. R group had significantly (p<0.05) lower in pH (vein blood gas test) and higher in blood uric acid (BUA) compared with those of NR group. These findings suggest that the elevation of BUA and acidosis in R group may induce the formation of renal calculus resulting in postrenal failure. Our patient is white male 9 y/o. At 4 year of age, he was Dx. with acute lymphocytic leukemia and was induced to remission on POG 9404; he presented tumor lysis syndrome during induction, acute renal failure with no recovery in renal function and RRT was started (CCPD) and continue on the same therapy. During the last years, he presented chronic pancreatitis, ARDS, sepsis. He had episodes of major vessel thrombosis probably due to central lines (several femoral lines and vascath placed in his thorax) and L-asparaginase. Our patient did receive 3 years of chemotherapy and radiation; and he is on complete remission. On 11/2,005, for pre-kidney transplant evaluation, a MRI test was requested using gadolinium 1 ml/kg for evaluating his vascular system (abdomen and pelvis) with inconclusive results. Another MRI test was requested 3 months later using gadolinium 0.3 ml/kg. 8 weeks later, his mother noticed brawny hyperpigmented, shiny, tightly bound-down, indurate plaques of his bilateral lower extremities, (more significantly on his lateral and posterior calves, and in his anterior and lateral thighs) A punch skin biopsy showed increasing number of fibroblastic cells and widened space between septa in the deep reticularis dermis compatible with NFD. NFD is a fibrosing disorder identified among patients with renal disease with cutaneous finding of skin thickening in extremities and trunk, very similar to those of systemic sclerosis. Etiology, pathogenesis and clinical course remain unknown. The majority of cases have been reported in dialysis or KT patients and gadolinium has been identified as a trigger of NFD. In our case, there appears to be a link between the use of gadolinium and the developed of NFD. Background: Chronic renal failure (CRF) is an independent cardiovascular risk factor. Changes in calcium-phosphate homeostasis not only affect the quality of bones but also constitute the biochemical base for vascular calcification. Aim: To find a method better describing factors of calcification using routine laboratory examinations and computed evaluation of complex equilibria. Methods, patients: Data of 12 CRF and of 24 transplanted (TX) children were compared to a healthy control group of 15. TX children's parameters were taken before and 12 and 48 month following transplantation. Three different strategies were used to analyse factors of calcification: Ca x P product, Ca-P activity value and the concentration of CaHPO 4 .

The Ca x P product and the Ca-P activity value were not informative, because they didn't represent the direction of change in the complex chemical equilibrium. The CaHPO 4 concentration was increased in the CRF and the TX group (before transplantation) (0.380±0.173 mmol/L) compared to the healthy control group (0.260±0.060 mmol/L) (p<0.01). After 12 and 48 months to transplantation the CaHPO 4 concentration was in the normal range in the Tx group. A negative correlation was found between the concentration of iCa 2+ (ionic calcium) and PTH (parathyroid hormone) in the dialysed children (r=0.720), but not in the transplanted group (r=0.122).

Conclusion: According our findings the force driving calcification is better represented by the concentration of CaHPO 4 , the base compound of all primary calcification, than by measuring Ca and P separately. Follow-up study is needed to establish the predictive value of determination of CaHPO 4 . This study was supported by grants OTKA-T046155 and ETT 435/2006, the National Office for Research and Technology (NKTH) and Szentágothai J. Knowledge Centre. Introduction: Acute renal failure is a rare complication of nephrotic syndrome and its cause is still unknown. Several investigators reported that the most important factor for renal failure was acute tubular necrosis (ATN); however, some cases did not have laboratory findings of tubular dysfunction paradoxically. Patients and Methods: We reviewed 11 cases of nephrotic syndrome with acute renal failure (NSARF) since 1990 at Metropolitan Kiyose Children's Hospital. Seven of 11 cases had calcium deposition in the distal tubules predominantly. We analyzed the clinicopathological findings in these 7 cases.

Results: The pathological diagnoses of these 7 cases were as follows: 4 minor glomerular abnormalities, 2 mesangial proliferative glomerulonephritis (without IgA deposition), and 1 focal segmental glomerulosclerosis. Interstitial nephritis was not documented in any case. The common characteristics of these 7 cases were calcium deposits in the distal tubules. Some cases had focal simplification of tubular epithelium. All cases were an initial episode of nephrotic syndrome, and 6 cases were steroid resistant. Almost all cases had hypertension. In addition, the range of urinary β2 microglobulin and FENa were 94 to 2980 and 0.1 to 0.33%, respectively. Discussion: In these 7 cases, there was enhanced Na reabsorption and urinary β2 microglobulin was only mildly elevated at the time of renal failure. These findings were not consistent with ATN. Additionally, pathological finding of severe tubular damages was not found on biopsy. Contrarily, tubular obstructions due to Ca depositions were consistent with these clinicopathological findings.

Conclusion: Our findings suggest that tubular obstruction due to calcium deposition plays an important role in the etiology of NSARF except for ATN. Background: Natriuretic factor was found in urine of chronic uremia for more than 30 years. N-Terminal Pro-B-Type natriuretic peptide (ProNTBNP) is postulated to be the natriuretic factor owing to its elevation in chronic kidney disease (CKD). However, salt wasting and non-saltwasting chronic kidney disease haven't been partitioned as different entities before. This study is designed to clarify whether ProNTBNP is different in salt wasting and non-salt wasting CKD and if it is the main causative factor of natriuresis.

Methods: 17 patients with salt wasting CKD, which are mainly composed of congenital renal structure abnormalities, and 11 patients with non-salt wasting CKD, which are mainly composed of glomerulonephritis, were collected. All of them are non-dialysis-dependent and without heart failure. Serum ProNTBNP in these two groups and 28 normal controls were sampled. Fractional excretion of sodium (FeNa) and estimated clearance of creatinine (Ccr) were also checked. Results: ProNTBNP was elevated in salt wasting group compared to normal controls (P=0.012). Moreover, ProNTBNP was even significantly higher in non-salt wasting group than in salt wasting one (P<0.0001). In salt wasting CKD, ProNTBNP and FeNa were correlated (R=0.7, P=0.017), but the same result was not observed in non-salt wasting group. ProNTBNP was significantly correlated to Ccr and age using multiple regression analysis (P<0.05). Conclusion: ProNTBNP elevation was different between salt wasting and non-salt wasting CKD. Volume expansion explained the difference and ProNTBNP elevation in salt wasting CKD resulted from other mechanisms. Since salt wasting CKD, in which the influence of volume expansion was eliminated, had a good correlation between ProNTBNP and FeNa, ProNTBNP may be one of the major contributing natriuretic factor in chronic uremia. Background: Cidofovir is a new antiviral drug that has a broad spectrum of activity against a number of DNA viruses. Several observations reported its efficacy as topical treatment of resistant warts. We herein report a systemic complication of acute renal failure associated with such topical therapy. Casereport: Girl aged 17, received a renal transplant in 1999 and 2001 for end-stage renal failure secondary to haemolytic uremic syndrome. Her initial immunosuppressive regimen consisted of prednisone, tacrolimusand mycophenolate. Five years post transplant she developed chronic allograft nephropathy with mild renal impairment. As a consequence of long standing immunosuppression she also developed invalidating, widespread periungueal warts. A well conducted, aggressive, conventional management of her warts including reduction of immunosuppression failed to improve the symptoms. She subsequently received an intralesional injection of a 75 mg/ml Cidofovir solution. Forty eight hours after the treatment she developed local swelling, inflammation and pain along with acute alteration of renal function. Although Cidofovir seric dosages performed on day 4, 5, 7 and 8 postinjection were negative we attributed this acute renal failure to a potential nephrotoxic side effect of Cidofovir. Renal biopsy showed no evidence of rejection but mild alterations of the tubes compatible with tubulo-interstitial nephritis. Spontaneous recovery of renal function occurred within 2 months. Conclusion: We describe an acute renal failure as a consequence of topical Cidofovir treatment of warts in the context of renal transplant with mild preexisting renal failure. Topical administration of Cidofovir needs as carefull use and monitoring as its parenteral administration, especially in patients with altered renal function. The Hemolytic Uremic Syndrome (HUS) is a disease characterized by microangiopathic hemolytic anemia and variable organ impairment with a predominat feature of renal failure in children. The aim of this study was to investigate the presence of plasma lipid peroxidation products in the acute phase of HUS. We have analyzed the levels of lipid peroxidation, determined fluorometrically as thiobarbituric acid-reactive substances (TBARs), in the plasma of 8 patients (aged 15-48 months with a median of 23) diagnosed with the shiga toxin-associated form of the disease. In all cases, TBARs determinations were performed at hospital admission, during treatment and upon discharge. TBARs values averaged 1.27±0.14 and 1.12±0.20 mM SEM at admission and discharge respectively (reference value <0.5 mM). Of the patients examined, 4 presented conserved diuresis during the course of the syndrome, while the other 4 were anuric and required dialysis. Maximum TBARs values resulted significantly higher (p<0.05 by ANOVA followed by Newman-Keuls test) in the dialysis-requiring patients as compared to those that had conserved diuresis (2.66±0.48 vs 1.58±0.39 mM respectively) We also investigated a possible correlation between TBARs and plasma creatinine, urea, lactate dehidrogenase (LDH) and platelet count. Positive and highly significant correlations (r=0.45 and 0.47, p<0.01) were observed when TBARs values were plotted as a function of plasma creatinine and urea values respectively. No significant correlations were detected for TBARs and plasma LDH values or platelet count. Thus, patients affected by shiga toxin-associated HUS exhibit increased levels of oxidative stress. Also, there is a positive correlation between the magnitude of oxidative stress and the severity of renal failure.

C. Soares, J. Diniz, E. Lima, G. Oliveira, C. Camargos, B. Sousa, E. Oliveira

Objective of the study: The purpose of this retrospective cohort study was to report the clinical course of children and adolescents with chronic kidney disease (CKD) enrolled in a pre-dialysis program.

Methods: The records of 108 patients with CKD admitted to an Interdisciplinary Pre-Dialysis program from 1990 to 2006 were retrospectively analyzed. The program consisted of conservative management of children and adolescents with CKD and was conducted by an interdisciplinary team including pediatric nephrologists, pediatricians, nurses, psychologists, nutritionists, and social workers. The patients were admitted with a glomerular filtration rate (GFR) equal to or below 75% of the value expected for their age according to normal reference data. Demographic, clinical and laboratory data at entry and at the end of the follow-up were analyzed. Renal survival analysis was performed using the Kaplan-Meier method.

Results: The median age at admission was 8.8 years (interquartile range: 2.6-13.2 yr). The most frequent primary renal disease was congenital urological anomaly in 50 patients (46%), following by glomerular diseases in 25 (26%), cystic diseases in 19 (18%), and others in 14 children (13%). At admission, 8 patients (7%) had CKD stage 2, 60 (56%) had CKD stage 3, and 40 (37%) presented CKD stage 4. Median follow-up time was 5.3 years (IQ range, 2.6-7.8). At the end of the follow-up, 12 children presented CKD stage 1 or 2 (13%), 20 patients were in stage 3 (18.5%), 16 in stage 4 (15%), and 58 children were in stage 5 (54%). It was estimated by survival analysis that the probability of CKD stage 5 was 24% at 3 years, 37% at 5 years, and 62%at 10 years after admission to the pre-dialysis program.

Conclusion: The long-term overall renal survival is relatively poor in a cohort of children and adolescents with CKD. Objective: Characterize the association between proteinuria and GFR in a cross-sectional study of children with mild to moderate chronic kidney disease (CKD). Methods: First morning urine protein to creatinine ratios (Up/c) and GFR (measured by Iohexol blood-disappearance) for 260 children enrolled in the CKiD cohort study were examined using loglinear regression of proteinuria and GFR, adjusted for age, sex, body surface area (BSA), and CKD cause. Conclusions: In children with mild to moderate CKD, there was a log-linear relation between proteinuria and GFR. The prospective cohort design of CKiD will assess the risk of GFR decline associated with level of proteinuria in children with glomerular vs non-GN causes of CKD.

Objective: To study the clinical characteristics of chronic renal failure (CRF) in children.

The clinical data of 81 children with CRF in the last fifteen years were retrospectively analyzed.

Results: The first main causes of CRF in children were still glomerular disease, and congenital deformities of urinary system and hereditary renal disorders were the second main causes. The initial age of children with CRF which were caused by congenital deformities of urinary system and hereditary renal disorders were relatively younger than children with CRF which were caused by glomerular disease. The symptoms of some CRF in children were not typical. Conclusions: Glomerular disease were still the first main causes of CRF in children. Urine screening test, early renal function examination and kidney B-mode ultrasonic were attribute to early diagnosis and proper management of CRF in children. The aim of the study was the evaluation of influence of clinical and biochemical parameters upon degree of impairment of cardiac function in dialysed children. Methodology: 16 chronically dialysed (6 HD, 10 PD) children participated in the study (10 M, 6 F), aged 5-18,5 yrs (x=12,2±3.8 yrs). Echocardiography examinations were carried out with a HP 5500 device. Diastolic and systolic left ventricular (LV) dimension, ejection fraction (EF) and LV mass index (LVMI) were evaluated. Mean values of estimated parameters in 6 months preceeding ECHO were calculated. Results: On the basis of ECHO examinations 3 groups were singled out: A (n=3) of normal heart function, B (n=3) of impaired systolic and diastolic heart function and C (n=10) of normal systolic and impaired diastolic heart function. No differences between groups according age, BMI, dialysis and renal insufficiency duration were found. In group of children with severe cardiac lesion (B group) a higher LV mass (A vs B vs C: 74,7 vs 119,9 vs 73,5 g/m) and statistically significant lower ejection fraction (68,1 vs. 33,7 vs. 65,9%) were ascertained. These children were anuric (996 vs. 0 vs. 1112 ml/d), their systolic (102,1 vs. 118,4 vs. 117,9) and diastolic (64,4 vs. 84,8 vs. 77,9) blood pressure were significantly higher, so was the number or hipotensive medications (0,33 vs. 1,72 vs. 1,44) . Bioimpedance analysis showed overhydration in group B (TBW% 63 vs 67 vs 62.5; ECW/ICW 0.67 vs 0.76 vs 0.7). Conclusions: The vast majority of chronically dialysed children demonstrate an impairment of cardiac function mainly of diastolic parameters. Anemia, malnutrition, hypervolemia, anuria and hypertension stand for a significant risk factors of cardiac impairment in dialysed children. We report here the clinical findings and prognosis of 10 patients (5 girls, 5 boys) with infantile oxalosis diagnosed between June 1990 and December 2006 in order to remind this rare autosomal recessive metabolic disorder as the potential cause of acute renal failure in infancy. The mean age of the patients was 4.7 months (range: 2.5-10 months). All patients had the complaint of vomiting since birth, 3 had irritability, and 2 had convulsions. Seven of them had parental consanguinity (70%) and family histories revealed urolithiasis in four patients and infantile deaths in one. Two patients were cousins without any other family history. All patients presented with anemia (hemoglobin: 4.5-9.6 g/dl), renal failure (creatinine levels: 3.2-10.2 mg/dl) and metabolic acidosis. Abdominal X-rays showed bilateral nephrocalcinosis, renal ultrasonographies revealed normal sized kidneys with diffuse and intensive hyperechogenity and loss of corticomedullary differentiation in all patients. Crystal deposition was demonstrated in fundoscopic examination of 5 patients, bone marrow aspiration of 2 patients, and renal tissues of 8 patients that underwent renal biopsy. Besides supportive therapy, peritoneal dialysis was performed on 7 patients, but only one patient accepted to continue the therapy. Four patients died within few months and 4 were lost to follow-up, probably died. Two patients have been followed up for 3 months one on continuous ambulatory peritoneal dialysis. In conclusion, this rare disease with fatal outcome should be remembered and investigated in infants with renal failure and bilateral nephrocalcinosis since early combined renal and liver transplantation may be life saving if it can be performed.

Acute Renal Failure Following Halothane Anesthesia in Young Child? Case Report We present here the case of renal failure and hepatocellular lysis that developed 24 h after the exposure of halothane anesthesia during eye examination. Previously a healthy 7 months old boy had a cardiac arrest, during the above mentioned diagnostic procedure, therefore CPR was applied which all happened in another hospital. After a few hours he was transferred to ICU at our hospital, consciousness, hemodinamic stabile. In the following 24 hours he developed acute non-oliguric renal failure (maximal level of urea 29 mmol/l, creatinine 259 mmol/l), as well as hepatocellular lysis (ALT 1879 U/L, AST 2157 U/L). Plasmaferesis and continuous venovenous hemodiafiltration were immediately applied followed by conservative measures. The level of serum transaminase returned to the normal values within a week and the level of creatinine and urea within two weeks. Fully recovered boy was released home. Toxic effects of halothane anesthesia in children are reported in only few cases in the literature. Objective of study: Many cases of chronic aristolochic acid nephropathy (CAAN) in adults had been reported, but it had rarely been described in children. We reported 3 children with CAAN to investigate its clinical and pathological characteristics. Methods: Three cases were studied retrospectively and relevant literatures were reviewed. Results: Three children received traditional Chinese herb medicine containing aristolochic acid 4 to 8 months for different basal diseases including chronic aggressive hepatitis B, secondary hydrocephalus and purpura nephritis and suffered from CAAN from 2 mouths to 6 years after they began receiving the Chinese medication. The main manifestations were renal failure of various degree accompanied with proximal and distal tubular dysfunctions. Two of them began with anemia and suffered from serious renal failure. The onset of another case was glucosuria with renal function impaired mildly, and she presented secondary Fanconi's syndrome simultaneously. Their pathological characteristics were diffuse paucicellular interstitial fibrosis and marked tubular atrophy with mild glomerular impairment. After withdrawal of the Chinese herb medicine, renal failure in two patients attenuated progressively.

The clinical features of CAAN in children are progressive renal failure and renal tubular disfunction. Its pathological characteristics are diffuse paucicellular interstitial fibrosis and marked tubular atrophy. Therefore, we emphasize the recognition of the nephrotoxicity of traditional Chinese herb medicine and prevent CAAN from happening in children. Objective of study: Recombinant human erythropoietin (rHuEPO) treatment may cause pure red cell aplasia (PRCA), but it had been rarely described in children. In order to acquaint ourselves with this disease, we reported a boy with chronic renal failure developed PRCA following rHuEPO treatment. Methods: One case was studied retrospectively and relevant literature was reviewed.

Results: A 10-year-old boy suffered from chronic renal failure combining with renal anemia and received rHuEPO treatment. Two weeks later, his hemoglobin (Hb) increased from 57 to 90g/L, and maintained 90 to 94g/L for 6 weeks. Subsequently his Hb declined suddenly at a rate of 1g/L/day, despite rHuEPO increased in dose. His reticulocyte count reduced to 0.4 10 9 /L without other cytopenias in peripheral blood. A series of laboratory examinations were performed, including bone marrow cell smear and culture to confirm his PRCA. Because various of other factors such as parvovirus etc. induced PRCA was excluded, we considered the boy's PRCA was due to rHuEPO treatment, although we didn't detect anti-EPO antibodies for lacking of the reagent. The boy received erythrocyte suspension transfusion to correct his anemia and was waiting for renal transplant in the following period.

Conclusions: During the treatment of rHuEPO, sudden and rapid reducing of Hb might be a hint of rHuEPO induced PRCA. The diagnosis should be based on the clinical presentation, the absence of red cell precursors in bone marrow and the detection of anti-EPO antibodies. Renal transplant and immunosuppressive therapy might be effective.

M. Zaniew, B. Mroziñski, A. Warzywoda, E. Stefaniak, A. Siwiñska, J. Zachwieja

Among ambulatory blood pressure monitoring (ABPM) parameters, pulse pressure (PP) provide an information on cardiovascular (CV) status. Recently, a novel parameter i.e. ambulatory arterial stiffness index (AASI) has been proposed. Aim: To investigate PP and AASI in relation to left ventricular (LV) geometry and carotid intima-media thickness (cIMT) in children with chronic renal failure (CRF). Subjects: 24 children (6 F/18 M; median age: 15 yrs) with CRF treated conservatively (n=8) and with dialysis (HD; n=7/PD; n=9). Methods: We studied demographic data, echocardiography data [left ventricular mass (LVM), left ventricular mass index (LVMI), interventricular septum (IVS), left ventricular posterior wall (LVPW), left ventricular end diastolic diameter (LVEDD), relative wall thickness (RWT)], cIMT and ABPM. From ABPM, we calculated PP [difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP)] and plotted DBP against SBP (regression slope). AASI was defined as 1 minus this regression slope. Results: A positive correlation was found between AASI and PP (r=0.35, p<0.05). AASI was correlated to LVEDD (r=0.39, p<0.05) and RWT (r=-0.45, p<0.01). PP was related to: weight (r=0.47, p<0.01), body surface area (r=0.41, p<0.05), body mass index (r=0.43, p<0.05), and LVM (r=0.58, p<0.001), LVMI (r=0.54, p<0.01), LVPW (r=0.35, p<0.05), LVEDD (r=0.68, p<0.001), RWT (r=-0.35, p<0.05). Neither AASI nor PP was associated to cIMT. Children with LV hypertrophy had higher PP than without this alteration (p<0.05). When data analyzed across quartiles of PP, children in the upper quartile showed higher LVM (inter-group comparisons p<0.001), LVMI (p<0.01), LVPW (p<0.01) and LVEDD (p<0.001). Conclusions: PP is a stronger predictor than AASI of LV geometry in children with CRF.. Acute renal failure in newborn period may be caused by prenatal, natal and postnatal factors. Among them, obstructive lesions of the genital tract (e.g. imperforate hymen and vaginal atresia) are very rare. Children with hydrometrocolpos due to distal vaginal atresia may present with severe obstructive uropathy and its consequences. Hydrometrocolpos is the result of vaginal obstruction and can become an emergency in newborn period. Acute renal failure associated with distal vaginal atresia appears to be rare, with only one report in the paediatric literature. Here we report a 27-dayold infant with a hydrometrocolpos causing life-threatening renal failure. Percutaneous drainage did result in dramatically improved clinical and laboratory findings of the patient.

Objectives of study: Sympathetic overactivity is currently considered as an important mechanism of both development and progression of chronic renal failure. However, this statement was mostly based on the researches in which the participants were adult patients with terminal renal failure. Little information is available on autonomic changes in pediatric patients with mild renal insufficiency. Our aim was to determine whether there is sympathetic activation in children with chronic pyelonephritis in a stage of mild renal insufficiency. Methods: 47 patients met the inclusive criteria were selected and assigned into two groups according to the creatinine clearance. Group I had 26 patients with creatinine clearance between 60 and 90 ml/min/1.73 m 2 while group II have 21 patients with normal creatinine clearance. Baseline of age (from 10-17 years old), gender and diagnosis between the 2 groups are comparable. Time domain analysis of heart rate variability in short-term recordings of 2 minutes was performed in both groups. As well Vain questionnaire for assessment of autonomic state was performed in all participants with their parents help.

Results: The outcomes of heart rate variability analysis showed sympathetic overactivity of 73.0% patients in group I vs 30.8% in group II, and the difference is statistically significant (t=2.497, p<0.05). Significant difference was also found in results of Vain questionnaire: 69.2% of patients in group I were estimated as "sympathetic", while only 33.3% in group II (t=2.32, p<0.05).

Conclusions: Based on the consistent findings of the two methods used in this study, we conclude that sympathetic overactivity may be found in children with even mild renal insufficiency, and it should be considered as an early event in the development of pediatric renal failure. 

The aim of this study was to describe the prevalence of myocardiopathy in pediatric patients with different stages of CKD (stages 2 to 5).Methodology: Inclusion criteria -GFR <75 mL/1.73 m 2 , CKD treatment >6 months, age <19 years old. Echocardiograms were performed using standard techniques. Left ventricular mass (LVM) was measured by two-dimensional directed M-mode echocardiography according to the American Society of Echocardiography criteria. LVM index was assessed and when >51g/m 2.7 it was considered severe hypertrophy. The relative wall thickness (RWT) was measured to assess the LV geometric pattern. Age, high blood pressure (HBP), anemia, time and type of treatment were compared to the echocardiographic findings. Results: We evaluated 53 patients, mean age 8 years old, 41% on pre-dialysis, 36% on hemodialysis (HD) and 23% on peritoneal dialysis (PD). Patients on HD were evaluated in the interdyalitic period. Twenty-seven patients (51%) had myocardiopathy, CLVH in 14 (25%), ELVH in 7 (14.5%) and CR in 6 (11%). Severe hypertrophy ocurred in 20 pacients (37.7%). There was no significant difference in relation to age and high blood pressure. Patients with CLVH were on HD for longer time and had a lower hematocrite when compared to the patients without CLVH (14±3 vs 4±2 months; p<0.01) and (33±1 vs 27±1; p<0.001) respectively. There was a significant correlation between hematocrite and left ventricular mass (r 2 =0.28). Conclusion: We observed a high prevalence of myocardiopathy in this study population. The risk factors associated to CLVH were anemia and time on HD. Larger and prospective studies are needed to analyze the impact of myocardiopathy in the cardiovascular mortality in children as well as the results of interventions applied to correct these risk factors. [0] [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] . Urological problems such as vesicoureteral reflux (18, 5%), obstructive uropathy (10,7%) and neurogenic bladder (15,1%) were the leading underlying conditions causing CRI with a total of 46,3%. While majority of the patients were having GFR levels less than 15 (33,5%) or between 25 to 50 ml/min/1,73 m 2 (31,2%), GFR level was between 50-75 in only 16.5%of the patients. Patients with PTH levels between 100-300 and more than 300 pg/ml comprised the majority (32,4 and 40% respectively). The GFR levels correlated positively with hemoglobin/hematocrit and calcium levels and negatively with phosphorus and PTH levels (p<0.05). Renal replacement therapies were initiated in 33,6% of the patients.

The most striking result of this study is the predominance of VUR or related urological problems that are relatively preventable as the underlying causes of CRI in children. Early diagnosis and appropriate medical or surgical management of these conditions should be emphasized together with achieving broader coverage of the pediatric CRI population in terms of supportive treatment.

Twin-twin transfusion syndrome (TTTS) complicates up to 15% of monochorionic twin pregnancies. Shunting of blood between twins through common placental blood vessels can cause growth restriction, oligohydramnios and anaemia in the donor twin. Renal impairment in the donor twin has been reported as a transient phenomenon with full recovery. We describe a case series of three children with chronic renal failure due to TTTS. All 3 cases were monochorionic diamniotic twins. In cases 1 and 2, growth discrepancy was noted on prenatal scanning. In the case 3 anomaly scans were normal. Gestation at birth ranged between 31 and 36 weeks. In all cases there was a significant birth weight discrepancy between twins. Post-natal ultrasound appearances were variable: case 1 had normal scans within the first month but echogenic kidneys at 3 months; case 2 had initial increased echogenicity but features consistent with cortical necrosis at 4 weeks; case 3 had small kidneys with no cortico-medullary differentiation. All 3 children became dialysis dependent within the first year of life. Age of commencement ranged from 4 days to 7 months. Case 3 was successfully transplanted at 3 years. Case 2 had an unsuccessful transplant at 2 years and remains on dialysis at 4 years. Case 1 remains on dialysis at 2 years. Cases 2 and 3 are now at mainstream school with only mild learning difficulties; case 1 has some gross motor delay but other wise normal development. With advances in neonatal intensive care and improved survival of low birth weight babies, this presentation may become increasingly common. Even severe renal involvement can occur in the absence of other significant hypoperfusion injury. The management of survivors of TTTS with established renal failure may present unique challenges and opportunities. Introduction: Endothelial heparan sulfate proteoglycans (HSPG) play an important role in various biological processes in the renal glomeruli. It is involved in the inflammatory process by acting as a ligand for L-selectin. Furthermore, leukocytes are able to interact with chemokines bound to HSPG (examples are IL-8, RANTES and MCP-1). This will lead to activation of the integrins on leukocytes and result in more stable leukocyte-endothelial wall adhesion. In this work, we have studied the effect of a subtoxic dose of shiga-like toxin (Stx) 1 and 2 on the HSPG and the possible implications on the pathogenesis of the hemolytic uremic syndrome (HUS). Methods: To study this effect, primary human umbilical venous endothelial cells (HUVEC) and primary human glomerular microvascular endothelial cells (GMVEC) were incubated for 24 hours with a subtoxic dose of Stx1 or 2. Then, cells were treated with the enzyme heparinase 3 (which cleaves off HSPG). Non-treated cells were used as controls. After treatment with the enzyme, the endothelial cells were exposed to flowing human leukocytes in a parallel plate flow chamber. The amount of adherent leukocytes was calculated.

-: not treated with heparinase 3, +: treated with heparinase 3 Conclusion: Stx1 and 2 cause an upregulation of the amount of adhering leukocytes on both endothelial cell types. Treatment of the endothelial cells with heparinase 3 decreases markedly this upregulation. The effect can not be detected without Stx-incubation. This can be explained by a possible upregulation of HSPG on endothelial cells by Stx, resulting in a higher level of bound chemokines or an increased binding of released chemokines to HSPG. This will lead to an increased adhesion of leukocytes and will induce a more severe inflammatory process in the renal endothelium. This effect will contribute to the devastating pathogenesis of the HUS.

C. Soares, J. Diniz, E. Lima, G. Oliveira, C. Camargos, B. Sousa, M. Almeida, E. Oliveira

Objective of thestudy: The purpose of this study was to identify clinical, nutritional and laboratory factors associated with the rate of progression of chronic kidney disease (CKD) among the children and adolescents admitted to a pre-dialysis interdisciplinary program. Methods: One hundred eight children and adolescents aged 2 months to 19 years with CKD in conservative management were prospectively followed up from 1990 to 2006. Renal survival was analyzed by the Kaplan-Meier method and Cox's regression model. A multivariate model was developed from the admission until occurrence of CKD stage 5 (glomerular filtration rate <15 ml/min). The following data were obtained at admission: gender, race, age at admission, weight Z score, renal primary disease, blood pressure, and laboratory data (serum creatinine, serum urea, glomerular filtration rate, 24 hr urinary protein excretion, hematuria). Results: Median follow-up time was 5.3 years (IQ range, 2.6-7.8) and 58 patients (54%) progressed to CKD stage 5. In the univariate analysis the following variables were significantly associated with the event: non-white race (p=0.04), age >8 years (p=0.01), CKD stage at baseline (p=0.01), renal primary disease (p<0.001), severe proteinuria (P<0.001). After adjustment, 3 variables remained as independent predictors of CKD stage 5: severe proteinuria (RR=2.1, 95% CI=1.4±3.1), glomerular disease as renal primary disease (RR=1.5, 95% CI=1.2±1.0), and CKD stage 4 at baseline (RR=2.3, 95% CI, 1.4±3.7).

Conclusion: The combination of three factors -severe proteinuria, glomerular disease, and CKD stage 4 at admission -was an independent indicator of adverse outcome in children and adolescents in a pre-dialysis interdisciplinary program. Background: Allogenic hematopoetic stem cell transplantation (allo-HSCT) has gained world wide acceptance as a treatment for various diseases. Renal dysfunction is one of the major complications that influences transplant related mortality (TRM) rates following HSCT. In this prospective study, we aimed to investigate the effect of allo-HSCT on renal function in children.

Methods: Renal ultrasonography, DMSA scintigraphy, analysis of renal and tubular function tests were performed before, shortly and 1-year after HSCT. Acute renal toxicity (ART) was classified according to Bearman criteria. Grade 1=increase in creatinine up to twice the baseline; Grade 2=increase in creatinine above twice baseline; Grade 3=increase in creatinine above twice baseline and need for dialysis. Chronic renal insufficiency (CRI) was defined as GFR<70 ml/min/1.73 m 2 and failure (CRF) as need for dialysis. Results: Between April 1999 and June 2006, 57 children (median age: 10.0 years) underwent 58 allo-HSCT because of hematologic disorders (malignancy, 19; hemoglobinopathy, 28; aplastic anemia, 10). All patients except one received nonTBI conditioning regimen. Six patients (10.3%) were died because of TRM but none of these patients had primary ART. During the first 100 days, 10 patients (17.2%) had grade 2 ART (CsA nephrotoxicity in 7, VOD in 3 patients). Grade 3 ART was defined in 5 patients (8.6%) (VOD in 3, sepsis in 1, CsA nephrotoxicity in 1 patient). Eleven patients had structural renal abnormalities before HSCT, 3 of them persisted and 3 new patients had pathologic results one year after HSCT. In long term period, 5 (8.6%) of 37 evaluable children had CRI and no patient had CRF requiring dialysis. Conclusion: Renal dysfunction was found to be a frequent complication after allo-HSCT in children. Therefore, renal functions should be followed carefully in these patients. .26 years and at the end of follow-up, and compared between the three groups. There were no significant differences between groups in so far as gender, underlying disease, age at diagnosis, proteinuria, hypertension, hyperparathyroidism, use of ACE inhibitors or renal size. Erithropoietin use was significantly higher (p<0.001) in Group 1. GFR improved in all three groups during their first two years of life. The cut-off point on the ROC curve indicating worse GFR long term evolution was 50 ml/min/1.73 m 2 at two years of life (sensitivity 85%, specificity 88%).

G. Zilleruelo, AM. Onder, J. Chandar, O. Nwobi, C. Abitbol

Background: Catheter-related bacteremia (CRB) is a common complication of tunneled-cuffed hemodialysis catheters. Our objective was to investigate the effectiveness of tissue-plasminogen activator-tobramycin locks (TPA-ABL) in preventing CRB in pediatric patients. Methods: A retrospective analysis of 52 pediatric hemodialysis patients was performed. Patients with >10 CRB/1000 catheter days (CD) were designated as high risk. Those with <10 CRB/1000 CD were of average risk. Three eras of 6 consecutive months were studied. In Era 1, high risk patients were detected. During Era 2, the high-risk group was placed on 3 times weekly prophylactic TPA-ABL. In Era 3 the high-risk group was given once weekly TPA-ABL.

Results: There was a significant decrease in the rate of CRB with prophylactic TPA-ABL which was more pronounced when given three times/week. Conclusions: The use of prophylactic TPA-ABL 3 times weekly significantly reduces the rate of CRB in patients at high risk. Prophylaxis once weekly may be less effective than thrice a week. L. was born after a normal pregnancy without a special personal or familial history, was seen at the age of 4 years, after a 6 days long ordinary oro-pharyngeal viral infection treated by symptomatic treatments. He presented with inflammation of the left cheek with slight fever (38°) and a sole purpuric lesion of the left leg (1cm) and some petechiae on the thorax. Blood count showed haemolytic anemia (haemoglobin=10 g/dl, schizocyte=2%, increased LDH), 23000 white cells (90% neutrophils) and 123000 platelets. No germs were found in hemoculture, lumbar punction, stools or urines cultures. Creatininemia was 95 μmol/L. In the following hours, despite immediate antibiotics administration and without any shock sign, several purpuric extensive necrotic lesions appeared, renal insufficiency increased (creatininemia=175 μmol/L), platelets count decreased to 46000 and markers of diffuse intravascular coagulation dramatically increased. In the following days, proteinuria, macroscopic hematuria and hypertension appeared. After 3 days on anticoagulation therapy, renal function remained stable while anemia, thrombopenia and coagulation disorders persisted. Coagulation factor tests demonstrated a heterozygote deficiency of factor V Leiden (also found in the father) and an acquired protein S deficiency secondary to streptococcal infection. After protein S infusion and plasma exchanges, his state improved and necrotic lesions ceased. This initial hematologic and renal presentation could have suggest a HUS but the large purpuric lesions remain unusual in such pathology.

A In children on Chronic Peritoneal Dialysis malnutrition is being diagnosed with an objective combined nutritional score (ABN score) based on anthropometry and bioimpedance analysis indices (Nephrol Dial Transpl 2006; 21: 1946-51) . Aim of this study was to investigate the prevalence of malnutrition and the main factors associated with it in children with CKD 2-4. We planned a cross-sectional study of 77 children with CKD 2-4, mean age 8.9±5.8 years, who underwent controls in our institution between September 1 and December 31, 2006. The data of ABN score, age, primary renal disease, standard blood and urinary tests, and estimated GFR (Schwartz formula) were collected.The prevalence of malnutrition (ABN score <10.33) in the whole population was 23%. The ABN score was positively correlated with age, height SDS, serum hemoglobin, total protein and albumin (p value from <0.0001 to <0.05), while a negative correlation was found with serum phosphate and proteinuria (p<0.005). Patients with steroid-resistant nephrotic syndrome had lower ABN score values than those with other primary renal diseases (9.61±0.85 vs 11.67±1.93; p<0.05). The percentage of children with malnutrition in the different stages of CKD increased in parallel with the decrease of GFR, from 10% in the CKD 2 group to 29.2% in the CKD 4 group. In conclusion, the prevalence of malnutrition in children with CKD 2-4 is not negligible. Low hemoglobin, total protein and albumin levels and high serum phosphate and urinary protein excretion, particularly in small children with growth impairment, strongly suggest the need for an in depth nutritional assessment, in order to diagnose malnutrition and treat it accordingly. E.C. developed atypical HUS at 6 months of age. A heterozygous factor H gene mutation was found. Despite plasma-exchange treatment numerous relapses led the child to CKD stage 4: creatinine clearance (CCr) 15.02 ml/min/1.73 sqm according to Schwartz formula. At 4 yrs we started a programme of fresh frozen plasma (FFP) infusions, 10-15 ml/kg BW. The child was poliuric and hypertensive, notwithstanding the treatment with ramipril, amlodipine, clonidine and furosemide. In the first 6 months he received FFP every 10 days. Mean CCr during this period was 16.8±1.7 ml/min/1.73 sqm. Haptoglobin (Hap) was still <20 mg/dl in 10/15 tests (66.7%), LDH was increased (543.9±87.5 U/l), hemoglobin and platelet count were always in the normal range. The treatment schedule was then changed to FFP every 7 days for the next 4 months. During this period, CCr was significantly higher (23.8±2.4; p<0.0001) and LDH significantly lower than in the first 6 months (445.5±31.7; p<0.005); haptoglobin was always >20 mg/dl. No differences between the two periods were found for hemoglobin, platelet count, proteinuria, microalbuminuria and blood pressure values. Both in the first and the second period, CCr was negatively correlated with LDH (r 2 0.40, p<0.0005) and with the bioimpedance analysis (BIA) measure of Resistance, which is an index of body hydration.

In conclusion: 1. The only signs of disease activity in atypical HUS can be minor abnormalities in laboratory tests, such as increased LDH and decreased haptoglobin levels; 2. FFP infusions are useful in maintaining HUS remission and preserving kidney function, provided that the treatment schedule is optimized; 3. BIA is useful in monitoring hydration status of children with CKD, especially those with poliuria and under ACE-inhibitors, as it allows for the correct interpretation of serum Cr values. Analgesic-antipyretic agents are commonly used medications worldwide for the treatment of pain and fever in children. Acute renal failure is commonly seen in adults after treatment with analgesicantipyretic agents. This complication has rarely been reported in children. Two patients, ages 12 and 16 years were admitted with a diagnosis of acute, non-oliguric renal failure. One had symptoms of upper respiratory tract infection, and the other had been suffering from vomiting and abdominal pain. Appropriate evaluations including detailed history especially the history of drug ingestion, physical examination, and measurement of serum creatinine concentrations were performed in the emergency department. Both patient had ingested analgesic-antipyretic agents (mefenamic acid, and paracetamol) before the onset of acute renal failure. None of the patients had previous history of renal disease or concomitant treatment with other drugs. None had oliguria or anuria, dehydration, abnormal serum electrolyte concentrations, or evidence of glomerulonephritis. Microscopic hematuria and leukocyturia were found in one patient. Serum creatinine was 1.1 and 2.29 mg/dl at presentation. Both of them recovered completely within a week. We emphasize that clinicians must be aware of renal toxicity of analgesic-antipyretic drugs with low doses. With the increasing use of over-the-counter analgesic-antipyretic agents, this association may become more prevalent. Cardiovascular disease is a main cause of morbidity and mortallty in patients with chronic kidney disease (CKD). The pathophysiology of cardiovascular disease (CVD) in CKD remains uncertain but nowadays sympathetic hyperactivity is recognized as an important mechanism involved. This observational and transversal study of 40 patients from five to 21 years old, submitted to dialysis or at least four months after kidney transplantation (KTx), without signs of transplantations rejections, with definite CKD and creatinine clearance of 50 ml/min or less. The subject (median age=14 years; 62.5% female) were classified accordingly with treatment modality: conservative (n=7), peritoneal dialysis (CAPD) (n=5), hemodyalisis (n=13) and renal transplantation (n=15) submitted to 123l-metaiodobenzilguanidine (123l-MIBG) planar and tomography scintigraphy and heart rate variability (HRV). Comparisons among groups were made using ANOVA and the association between variables was assessed using Spearman's correlation coefficients and Bonferroni correction was used during multiple comparisons testes. A p value <0.05 was considered significant. Hemodialysis patients presented increased cardiac washout (p=0.002), heterogeneous pattern of 123l-MIBG distribution (p=0.036) and lower values of Low Frequency component of HRV (p=0.040). CAPD subjects had reduced lung washout (p=0.030). The cardiac washout had positive correlation with PTH and negatives correlation with creatinine clearance. There was a significant negatives association between the RR interval in Low Frequency (LF) and cardiac washout. The uremic cardiac disautonomia might be characterized by decreased Low Frequency component of HRV and increased 123l-MIBG washout and heterogeneous distribution pattern by left ventricular walls; these abnormalities subsided after KTx. D+HUS is the main cause of acute renal failure in children. Extrarenal manifestations are associated in more than 30% of the cases. HUS causes toxin mediated endothelial cell damage, resulting in thrombotic microangiopathy and intraluminal thrombosis of small vessels, with subsequent tissue ischemia and necrosis of involved organs. A 3-year-old boy has been admitted for D+HUS associated with Escherichia coli O145 diarrhea. He presented with renal failure and hypertension requiring hemodialysis for 28 days, hemolytic anemia (5g/dl, schizocytes 6%) requiring 7 blood transfusions, severe thrombopenia (10 G/L) and hyperleucocytosis (39600/mm 3 ). Severe hemorragic colitis with duodenitis required prolonged parenteral nutrition. At 6 days after onset, the child presented with confusion, slurred speech followed by loss of consciousness associated with major hyperglycemia (107 mmol/l) and elevated corrected natremia (155 mmol/l) without ketosis requiring transfer in intensive care unit (ICU). Continuous hemofiltration associated with insulin therapy (0.05 UI/kg) was then established with slow decrease of natremia and serum glucose within 72 hours. Neurologic condition rapidly improved. Serum amylase and lipase were normal. Insulinemia at the same time as the highest hyperglycemia was low (1,7 UI/ml), and search for human insulin, islet cell and glutamic acid decarboxylase antibodies were negative. Insulin therapy could be discontinued within 15 days. At the last follow-up, 6 months later, neurologic examination, serum glucose and glomerular filtration rate were normal.

In conclusion: 1/ hyperglycemic hyperosmolar coma is a severe complication yet never reported in D+HUS; 2/ continuous hemofiltration with constant monitoring of biologic parameters could avoid permanent lesions due to rapid correction of this major metabolic unbalance. Chronic renal failure (CRF) can interfere with the regulation and time dependent secretion of multiple hormones. Adrenocortical function in children with CRF is examined in a few studies with a limited number of patients, and the results are controversial. In this study our aim is to evaluate adrenocortical function in basal and stimulated conditions, and to determine the relationship with the glomerular filtration rate (GFR), etiology and duration of CRF in a larger group of patients. Sixty-one patients with CRF (28 F, 33 M; mean age 12.6±3.2 years) were studied. The patients were grouped according to etiology [structural abnormalities (n: 33), glomerulonephritis (n: 11), others (n: 11)], duration of CRF [0-36 (n: 25) , 36-72 (n: 22) and >72 months (14)] and GFR [ 25-75 (n: 24), 10-25 (n: 19), <10 ml/min/1.73 m 2 (n: 18)]. Cortisol levels were measured at 08: 00 a.m. (basal cortisol) and 11: 00 p.m. Low dose ACTH test (0.5 micg/m 2 Synacthen iv) was performed. Delta cortisol was calculated as peak cortisol minus basal cortisol during the ACTH test. Diurnal rhythm is accepted to be preserved if 08: 00 a.m. cortisol/11:00 p.m. cortisol is greater than two. Basal cortisol levels and peak cortisol response to low dose ACTH is similar in all groups. Median levels of delta cortisol found to be higher in the GFR<10 ml/min/1.73 m 2 group; p=0.06. Diurnal rhythm seems to be more preserved in the GFR 25-75 ml/min/1.73 m 2 group (%68) compared to GFR<10 group (%44); p=0.612. No correlation was found between the basal, peak and delta cortisol, GFR and duration of CRF.

Our preliminary results have shown that there is no difference in the basal and peak cortisol levels between all groups. This is the first study in children showing that adrenocortical function is preserved in groups with GFR levels between 10-75 ml/min/1.73 m 2 . Objective: This study was we evaluated BK virus and JC virus in urinary after renal transplantation. Methods: Because these polyoma viruses are excreted in urine, these 12 patients (7 females and 6 males, 16.1±6.7 years old) was analyzed by polymerase chain reaction. All patients were living donor renal transplantation from a parent. Results: Two patients have detected BK virus in urine. As the type of immunosuppressive treatment, one had tacrolimus and mycophenolate mofetil, and one more had methylprednisolone and tacrolimus. Seventeen percent of the patients had quantifiable BK virus-DNA in urine. Thirty-three percent of the patients had quantifiable JC virus-DNA in urine. There was non significant relationship between these polyoma viruses in urine and the type of immunosuppressive treatment.

No patients developed interstitial nephritis during the study.

Conclusions: The activation of BK virus and JC virus does not seem to be related to the type of immunosuppressive treatment. The pathogenetic role of polyoma virus infection in renal transplantation recipients further researches are needed. Background: urinary tract infection (UTI) due to neurogenic bladder, secondary to large spina bifida as myelomeningocele, is well known, but the association of small occult spina bifida (SBO), having normal physical examination, with that of infection has not been reported. We studied the frequency of spina bifida occulta in children with urinary tract infection. Method: the KUB of voiding cystouretrography in 104 patients (72 F, 31 M) with average of age 6 year (±3.5 SD), who referred to radiology department of Ali Asgar Children Hospital for UTI, were observed for SBO. All patients had normal physical examination. Chi2 were used to find the frequency of the level of SBO and the differences respectively. P<0.05 was considered significant. Result: 80 out of 104 patients had SBO. The order of frequency of the level of SBO was S1 (51%), L5 (14,4%), S1S2 (6,7%), L5S1 (4,8%), and L5S1S2 (1%). 22 patients had vesicoureteral reflux (bilateral in 8 cases, 10 at left and 3 at right side). The severity of VUR was 76% grade (G) II, 14,35% G III, 9.1% G IV, and 4.8% G I. Spina bifida occulta was detected in 19 out of 23 patients with VUR. This difference was not statistically significant (p=0.43): Conclusion: the high frequency of lumbosacral SBO in the patients with urinary complaint may imply some lower urinary tract dysfunction in these patients although we need a control study in normal children. We evaluated interleukin-6 and interleukin-8 levels in the urine of 33 children with renal scarring, with vesicoureteral reflux (23/33, group A 1 ) and without vesicoureteral reflux (10/33, group A 2 ) and in the urine of 7 healthy children (group B). None of the children had urinary tract infection for the last ten months. Interleukin-6 and interleukin-8 were determined using a commercially available human enzyme-linked immunosorbent assay kit. Results: urinary interleukin-8 levels were below the lower detection limit in all samples. Interleukin-6 levels were detectable in all urine samples of children with renal scarring and below the detection limits in the urine samples of healthy children. There were no statistically significant differences between urinary interleukin-6 levels in children with and without vesicoureteral reflux. There is a relationship between the grade of renal scars, the time past from their development and the urinary levels of IL-6. 

The introduction of mycophenolate mophetil (MMF) was an important advance in immunosuppressive therapy but its use is associated with gastrointestinal intolerability (GI) requiring dose reductions or drug interruptions. Enteric coated mycophenolate sodium (EC-MSP) was designed to improve mycophenolic acid (MPA)-related GI by delaying the release of MPA until reaching the small intestine. At present, its immunosuppressive activity in pediatric renal transplant with GI has not been clarified. We studied trough levels of active metabolite MPA (C 12 ), changes in kidney function, mixed lymphocyte culture, cytotoxic antibodies as well as cytotoxic response before and after 3 months of the conversion from MMF to EC-MPS in 8 renal transplant recipients with GI. In the immunosuppressive protocol used: MMF, tacrolimus and corticosteroid, MMF 444±46 mg/m 2 /day was replaced by EC-MPA 318±34 mg/m 2 /day. After 3 months of treatment with EC-MPA, the incidence of GI decrease to 12.5%. The levels of MPA were about 50% higher on EC-MPS (6.9±1.1 ug/ml) compared to MMF administration (4.2±0.9 ug/ml). Serum creatinine, creatinine clearance and urinary protein excretion did not change (1.3±0.3 to 1.4±0.3 mg/dl, 71.7±10.3 to 70.2±10.4 ml/min/1.73 m 2 and 0.08±0.06 to 0.12±0.06 gr/24 hr, respectively). Also, during EC-MPA, proliferative response and cytotoxic antibodies showed no significant change. The release of IL-10 was striking augmented with MMF or EC-MPS therapy, but interferon-γ and TNF were low under both treatments. Our data indicate that conversion from MMF to EC-MPS leads to an improvement in GI without altering key elements of immunosuppression. However, the monitoring of MPA before and after conversion should be appropriated to the optimization of therapy efficacy.

Re. Munarriz, Ju. Arakaki, Ce. Munarriz Pediatric Clinic, Pediatric Nephrology, Buenos Aires, Peru

Objective: to describe the results of a program of chronic ambulatory peritoneal dialysis (CAPD) in children in Peru by means of conventional indicators. Methods: 61 children (52, 45% male) were included in a longitudinal descriptive study. The average age was 10, 4±4,02 years (rank of 1, [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] . 42% were from Lima (the capital city) and 58% came from other cities of the country. Primary glomerulonephritis (46, 1%) was the main cause of the renal insufficiency. We evaluated the program from 2001 to 2006. Results: the average weekly Kt/V was 2,8±1,13. The average dose of erythropoietin (EPO) was 98 UI/kg/week. 60% of the patients had average annual albumin of more than 3,5 gr./dl. The average annual protein catabolism index (ICP) was 1,0±0,37 gr/kg/d. The weight/age, height/age, weight/height Z scores at the beginning and at the end were 2.1/1.3, -2.095/1.3, -2.9/2, 4 -3.4/2.2, 1.9/7.0-0.8/2.1, respectively. The average hematocrit was 26.5±7.6%. The rate of peritonitis adjusted for the period was 0, 62 episodes/patients-year (1 episode every 19 months) and the mortality for the same period were 14%. Conclusions: the indicators evaluated in our patients are according to the results of the international literature.

Is Repeated Urine Culture Essential after Antibiotic Therapy in UTI in Thai Children? Background: In 1999, the American Academy of Pediatrics recommended for UTI treatment, that urine culture be repeated only in children <2 years with fever >48 hours, since the chance of a positive urine culture in other children is very low. Objective: To evaluate the cost-effectiveness of repeated urine culture after antibiotic therapy in childhood UTI. Patients and Methods: A retrospective review of the records of children diagnosed with UTI in Songklanagarind Hospital from Jan 1-Dec 31, 2004. Results: There were 479 patients total, of which 30 were excluded due to no repeated urine culture. 449 patients with 533 UTI episodes were analyzed (245 boys and 204 girls). 241 (53.7%), 71 (15.8%) and 137 (30.5%) patients aged <1, 1-2 and >2 years respectively. 49 (9.2%) had a repeated urine culture with significant growth. Multivariate analysis showed that age <1 year, etiologic agents Psuedomonas aeroginosa or Enterococci spp., fever >72 hours and KUB anomalies were the most significant risk factors for positive repeated culture, while VUR and recurrent UTI episodes were not significant risk factors. If we consider that a child who has at least one of the above risk factors should have a repeat urine culture, then 351 cases (65.9%) will require repeating urine culture and 182x3.7=$US 672.4 will be saved and 5 (10.2%) positive repeated urine culture will be missed. Conclusion: Our study in a group of Thai children indicates that repeated urine culture after antibiotic therapy is still recommended. Our aim was to find out if there are any signs of renal scarring and reduced renal function without recurrent UTI in patients with obstructive pyelonephritis. There were investigated 18 children (4-12 y) with 1-4 years passed after diagnosis of obstructive pyelonephritis. These patients were investigated during 2 years long period without UTI. All the children had a treatment with nitrofurantoin during season viral infections. We investigated excretion with urine of the collagen product (hydroxyproline) and activity of lisosomal enzymes (b N-acetilglutamase, elastase, pseudocholiesterase). As a control group, 20 healthy children of the same age were investigated. Our result demonstrates the decrease of the level in urine of collagen product and lisosomal enzymes and normalization of tubular and glomerular functions during 2 years remission of pyelonephritis. Prevention of recurrent UTI and maintenance of the remission of pyelonephritis leads to the decrease of sclerosing processes on kidney. Regular dialysis induces insecurity and special psychological problems associated with staff-, machine-and artificial material-dependence. The more severe the child's physical problems are the more probable is developing of emotional disorders, a sense of loneliness and an exaggerated dependence on the parents and staff. A psychological and social study of 19 children on regular dialysis was performed. There were 8 girls and 11 boys, aged 5-18 (mean: 11) ys. Two children (10%) are exclusively treated with haemodialysis, 11 (58%) are on peritoneal dialysis and in 6 (32%) both methods interchanged. Somatic concomitant disorders are present in 5 (26%) of children. Among psychological disorders, an inclination to unsociability, autoaggression or aggression towards the immediate environment has developed in 4 children (21%), 6 (32%) do not like talking about disease while 9 (47%) are communicative and sociable. Psychosocial characteristics showed: emotional difficulties (anxiety, mild depression) in 32%, feeling of being physically different from peers (short stature, less physical ability) in 42%, lowered self-esteem and social isolation as a result of school absenteeism in 26%. Overprotection of parents was presented in 58%. Different psychological changes were present in some children. Of the 19 children 17 are of school age: 3 (18%) attend special schools and the remaining 14 follow regular education programs. With the help from their teachers, children on dialysis can master regular school programs, in spite of the time spent on dialysis. A good and continuing co-operation of dialysis staff and sick children and their parents as well as a more intensive co-operation with psychologists and teachers are necessary to reduce psychological disorders and promote a better adaptation to the life of their healthy coevals. We report a 15-year-old girl with syndrome Frasier who developed B cell lymphoma within nine month after live related kidney transplantation. In induction therapy we applied ATG up to 5 days, mycophenolate mofetil and cyclosporine. Routine abdominal ultrasound revealed multifocal hypoechogenic changes in liver and spleen. Computed tomography showed diffuse focuses of changed liver tissue in length up to 4.5 cm, precontrast density of 30-40 HU and postcontrast of 50-65 HU. In spleen there were three similar changes (up to 2.3 cm). After surgical biopsy of liver, patohistological examination confirmed diffuse large cell B lymphoma (CD 20 positive, moderate risk). PCR EBV was positive. We immediately started with ganciclovir intra venously and decreased cyclosporin and MMF (within two weeks) up to completely exclusion from therapy. In the same time we increased prednisolon on 15 mg daily. After 7 weeks from beginning ganciclovir she treated with rituximab, one dose of 500 mg every week (five weeks). Repeated abdominal ultrasound and two controls computed tomography showed markedly regression of tumorous lesions. After 6.5 months of last rituximab doses scan showed normal spleen and liver findings. All lesions were resolved. In two occasions she developed severe leucopenia without any infection complication. She still has got moderate lymphopenia due to continual ganciclovir therapy. During this period (11 months) of illness course she treated with ganciclovir intravenously due to repeated EBV reactivation (positive PCR). Despite enormous reduction in immunosupressive therapy renal function remain stabile without episodes of acute rejection. 5-20.5 years) . The most of them, 92% (23 patients) received graft from live related donor. 84% of patients had preoperative dialysis and 14% were preemptive. The mean waiting period for transplantation was 30 months (range 0 to 120 months). Congenital anomalies of kidney and urinary tract were the most common underlying diseases (13 patients), then nephrotyc syndrome (4 patients), hereditary nephritis (3 patients), polycystic kidney disease (2 patients) and others. Daclizumab was the most commonly used as immunosuppressive induction agent and the maintenance immunosuppressive therapy consisted of azathioprine or mycophenolate mofetil (MMF), cyclosporine or tacrolimus and prednisone. Two patients had immediate postoperative surgical complication and graft loss due to thrombosis of a. renalis and donor tubular necrosis respectively. Three patients had delayed graft function; two of them underwent cadaveric transplantation. One patient had recurrence of primary kidney disease only few days after transplantation and graft loss after one year. Other patient lost the graft after 2 years due to noncompliance and chronic cellular rejection. After one year of follow-up graft survival rate is 86% and patient survival rate 100%. At the end of follow-up (mean range 29.21 months), 18 patients had normal, 3 patients slightly decreased renal graft function. Catch-up growth was seen during the first year after transplantation from mean height SDS of -1.65 to 1.25. The mean goal of our further intention is improvement of cadaver renal transplantation.

J. Lee, Y. Shim, S. Lee

Objectives; Although the variable risk factors of urinary tract infection (UTI) in children such as virulence factors of the pathogenic bacteria and vesicoureteral reflux are already well known, the role of normal flora clononizing the intestinal tract and genitourinary tract is not fully understood. The change in colony forming units (CFU) of Lactobacillus in chidren with UTI is primarily investigated to explore the role of Lactobacillus, one of the human normal flora, in development of UTI.

Methods; Lactobacillus was cultured from stool, urine, and periurethral or vaginal discharge of febrile infants with UTI. Those with confirmed UTI by the suprapubic urine culture were classified to UTI group (n=-60), and those with negative urine culture and confirmed viral illness were classified to control group (n=31). Lactobacillus was anaerobically cultured in Dico Rogosa SL agar (Becton, Dickinson and company, USA) for 48 hours at 37°C. Results: The CFU of Lactobacillus in stool was correlated with those in periurethra, vagina and urine (P<0.05). The CFU of Lactobacillus in stool was significantly lower in UTI group than in control group (19,286±30,920 vs 16,969,129±89,717,956, P<0.05) . The CFU of Lactobacillus in periurethra or vagina was significantly lower in UTI group than in control group (2,788±5,365 vs 43,038±179,089, P<0.05). The CFU of Lactobacillus in urine was significantly lower in UTI group than in control group (173±469 vs 2,087±5,681, P<0.05). The CFU was distributed mostly at low level in UTI group, which was significantly different from that in control group (P<0.05) Conclusions; The CFU of Lactobacillus in stool, periurethra, vagina and urine is low in infants with UTI. It is suggested that Lactobacillus has a role in the development of UTI. Pediatric small bowel transplantations are associated with pronounced electrolyte inbalances in the posttransplant period. We investigated the sources of possible electrolyte losses. Our hypothesis was that electrolyte inbalances after intestinal transplantation might be augmented by FK 506 (tacrolimus) mediated renal toxicity rather than short bowel syndrome alone. We retrospectively reviewed eleven living-related small bowel transplantations between October 2002 and December 2006. The data collected included frequent serum and urine electrolyte profiles, renal function parameters, enterostoma electrolytes, and FK 506 levels in the postoperative period up until either discharge or graft loss. We analyzed Pearson's correlations between FK 506 levels, serum electrolytes, renal function parameters, and also fractional excretions (FE). In order to investigate possible delayed nephrotoxic effects of FK 506, we correlated all values of the same day as well as with FK 506 levels of 24, 48, and 72 hours earlier. Furthermore, we analyzed our data stratified by FK 506 dosing ranges. Our results show decreased GFR and prominent increase of renal sodium, phosphorus, and magnesium losses along with rising FK 506 levels, suggesting this pathway as a major contributor to their imbalances. Furthermore, FK 506 levels were associated with serum calcium and phosphorus decline, though urinary calcium excretion was not significantly changed. Signs of renal toxicity are apparent within the first 24 hours of FK 506 challenge. Our data suggest that FK 506 mediated nephrotoxiticy is a significant contributor to electrolyte imbalances observed after small bowel transplantation. Objectives of study: Urinary tract infections (UTI) are common in children and C-reactive protein (CRP) in serum is often used to evaluate the severity of the renal inflammation. Recently it was demonstrated that CRP can be produced locally in the kidney. We therefore measured the CRP concentration in both serum (s-CRP) and urine (u-CRP) from children with UTI to evaluate the extent of local production and the usefulness of measuring u-CRP for diagnosis of inflammatory kidney disease. Methods: 56 children (31 boys) with UTI were studied (median age 0.8 years, range 12 days-5 years). 43 children had fever 38.5 °C or more. The UTI was caused by E.coli in 50 patients. All children were examined within a few days of diagnosis by DMSA scan for evaluation of renal function.

As controls were used 14 children with respiratory infection (pneumonia in most) and elevated s-CRP in whom UTI was ruled out by negative urine culture. U-CRP was measured in a commercial hsCRP ELISA. Normal value was <6 mg/L Results: In the UTI patients, the median s-CRP was 126 mg/L (range 0-440) and u-CRP 144 mg/L (range 0-937). There was a significant correlation between the s-CRP and u-CRP concentrations (<0.001). DMSA scans were abnormal in 37 (66%) UTI patients. The proportion of abnormal scans increased significantly with the CRP concentration in both serum (<0.01) and urine (<0.05). All control patients had increased s-CRP concentrations (median 157 mg/L, range 45-243) but the median u-CRP was 2.5 mg/L (range 0-73). The u-CRP in the patients with UTI was significantly higher than in the controls with other infections (<0.05). Conclusions: Our data strengthens the concept that CRP can be produced locally in the kidney during UTI. The usefulness of measuring u-CRP to evaluate inflammatory kidney disease needs to be tested further.

S. Paunova, A. Kucherenko, I. Smirnov, G. Serova, I. Donin, L. Revenkova, N. Goltsova

In order to reveal the role of cytokines in renal tissue damage in infants with urinary tract infection (UTI) 42 patients aged from 0 to 6 months were examined. In all of them inflammatory markers (ESR, CRP, leukocyte count), urine concentration of tumor necrosis factor-α (uTNF-α) and transforming growth factor-β (uTGF-β) standardized to urinary creatinine concentrations were evaluated. Two groups of patients were determined: 1) with UTI and normal urodynamics (n=33), 2) with UTI and urodynamic disorders (VUR, hydronephrosis) (n=9). 12 healthy infants were used as controls. As a result, all the patients demonstrated significantly elevated uTNF-α, uTGF-β creatinine ratio in comparison with controls (p<0,05) with no difference between groups. But 16 children with normal urodynamics (from the 1 st group) presented with severe UTI (1 st -A) showed urine TNF-α TGF-β creatinine ratio in 1,5 times higher than other patients of 1 st gr and close to 2 nd gr. data (1 st gr.-uTNF-α/uCr=9,32±1,82, uTGF-β/uCr=1231,65±133,36, 1 st gr.-uTNF-α/uCr=6,89±0,98, uTGF-β/uCr=782,7±87,77; 2 nd gr -uTNF-α/uCr=12,58±4,25, uTGF-β/uCr=1130,58±280,45, p1,2-1<0,05) . To conclude, TNF-α and TGF-β are responsive for renal tissue impairement in infants with UTI. Elevated TNF-α TGF-β creatinine ratio in a part of infants with normal urodynamics suggests that renal damage begins early in infection mostly due to inflammation. One may suspect a predisposition of that subgroup of patients to fibrogenic process and subsequent scar formation. Prompt diagnosis and localization of pyelonephritis are of great importance in treatment and prognosis of the patients. The urinary excretion of enzymes, in particular N-acetyl-beta-Dglucosaminidase (NAG), is considered a relatively simple and non-invasive method in the detection of renal tubular function under various conditions such as pyelonephritis. This study was performed to determine the diagnostic value of urinary NAG in acute pyelonephritis and to compare it with other indices traditionally used for this purpose in children. This is a Quasi experimental study conducted from April 2005 to May 2006 on children with pyelonephritis. Diagnosis of pyelonephritis has been based on standard criteria. Seventy-two patients between 1 month and 15 years were recruited. Fresh random urine samples were obtained on the admission time and at 48 th hour of treatment and were tested for NAG and creatinine. There was a significant difference in pre and post-treatment urinary NAG/Creat ratio (P<0.000) and the sensitivity and specificity of urinary NAG in diagnosis of pyelonephritis were 72% and 78% respectively. There was a significant correlation between urinary NAG level and kidney ultrasonography results. Patients whose ultrasonography showed hydronephrosis, had the highest level of urinary NAG and patients who showed urinary stone in their ultrasonography had the lowest level of urinary NAG. In addition, there was a reverse correlation between urine culture results and urinary NAG level; patients who had negative urine culture had higher level of urinary NAG in comparison with patients with positive urine culture. We conclude that urinary NAG is elevated in children with pyelonephritis especially in the presence of urinary tract abnormality and the absence of renal stone. Type-1 hyperoxaluria (PH-1) is an autosomal recessive disorder caused by the impaired activity of the hepatic peroxisomal alanine-glyoxilate aminotransferase. The disease leads to end stage renal disease (ESRD) and combined liver-kidney transplantation (CLKT) is required. We report 3 cases diagnosed with PH-1 who received CLKT. Case-1: She had attacks of dark urine without any pain and renal stones were determined on sonography when she was 2.5 years old. She was diagnosed with PH-1 and received peritoneal dialysis (PD) at the end of the first year and cadaveric CLKT was performed when she was 9 yearsold. At the age of 16, she had chronic allograft nephropathy and began to have hemodialysis (HD). Recently, 1.5 year after HD, cadaveric renal transplantation (tx) was performed. She is well after the second tx. Case-2: He was admitted with polyuria, polydypsia, stomachache and renal stones were determined on sonographic examination. He had ESRD and PD was started when he was 7 years old. At the age of 10, CKLT was performed from his mother. His liver and renal functional tests are well 8 months after CKLT. Case-3: He was evaluated because of having an older brother diagnosed with PH-1 when he was 4.5 years old. He had no complain, but sonography showed multiple calculi. Within 5 years he experienced flank ache, hematuria attacks and anuric phases due to obstruction and ESRD appeared and he received HD and CLKT was performed from his full-match sister at the age of 9.5. He is doing well 5 years after tx.

Here, we present the favourable clinical outcomes of our patients with CKLT to indicate the validity of this treatment of choice in PH-1. Tenascin (TN) is a glycoprotein component of extracellular matrix (ECM) which is not present in the normal kidney tissue. Tissue plasminogen activator inhibitor-1 (PAI-1) regulates fibrinolysis and the plasmin mediated matrix metalloproteinase activation and it is also not expressed in the normal kidney. Recent studies focus on the pathogenesis of advanced renal diseases. In this study we evaluated TN and PAI-1 staining in the renal tissues of pyelonephritic rats using immunohistochemistry (IHC) as to understand if these markers may be served as histological parameters of pyelonephritis like fibrosis, tubularatrophy or vascular changes. Seven rats were injected 0.1 ml solution containing E. coli ATCC 25922 10 10 cfu/ml into left renal medullae. Seven rats were designed as sham group and were given 0.9% NaCl. Rats were sacrificed 7 days after injections. Renal tissues were studied histopathologically by hematoxylin and eosinand scored for the parameters of pyelonephritis. TN and PAI-1 expressions were studied semiquantatively by IHC by Tenascin Novocastra (NCC-Tenas-c) and PAI-1 (H-300) Santa Cruz Biotechnology. Both TN and PAI-1 expressions increased in the pyelonephritic groups. We observed acorrelation between tenascin and fibrosis, vascular changes and tubular atrophy and PAI-1 expression showed a correlation with only fibrosis. We conclude that increase in renal TN and PAI-1 expression shown in experimental pyelonephritis are the responsible factors for the fibrotic changes of persistent renal damage.

Introduction: Urinary Beta 2 Microglobulin (β2MG) urinary excretion is a good index of proximal tubular cell dysfunction.

Objective: To determine β2MG excretion significance in determining the outcome in respect to scar and renal insufficiency. Patients and Methods: Urinary β2MG and Creatinine (Cr) was measured in 83 urine samples of whom 53 proceed to do DMSA renal scan at the time of admission and 6 months later to detect scar. β2MG was measured using radioimmunoassay method using β2MG 96-test kit (RADIM Company). Twenty children had various grades of renal scars. Results were compared with ratios of 19 children with low uptake and 14 normal scanning and 30 normal children. Student t test, ANOVA, and unpaired t-test was used for analysis and differences considered significant if p<0.05. Results: The mean urinary β2MG/Cr was significantly higher in the scarring group (5.23±10.6) than in the normal group (0.19±0.2) and in low uptake group (0.49±0.86) (p<0.05). Patients with grade III had higher values (14.69±15.82) than grades I (0.36±0.35) and II (3.37±5.20) (p<0.05). Patients without renal scar had β2MG/Cr ratio below 0.46 microgram/mg. The mean β2MG/Cr was higher in patients with VUR grades 4 and 5 (8.93±12.01) than patients with VUR grades 1 to 3 (0.81±3.04) (P=0.02). Maximum β2MG/Cr was detected in patients with grade 4 VUR (33.3) and the minimum was zero in non-refluxing patients and normal children. Two patients with high grade VUR and the highest levels of β2MG/Cr ratio (33.3 and 26) progressed to renal failure in 2 years time, the first patient was treated by hemodialysis and the second underwent renal transplantation. Conclusion: Measurement of urinary β2MG is useful in the early detection of tubular damage in patients with renal scars. Introduction: Chronic allograft nephropathy refer to the progressive decline of renal function seen in some renal transplant recipients in association with alloantigen-dependent and alloantigenindependen factors. Hyperlipidemia is a risk factor for chronic allograft nephropathy in adult pts, where no data exist in pediatric transplant population. Methods: In this cross sectional study, 62 patients (32 CAN/30 non-CAN) that aged 5-18 yr and 9-93 mo (mean: 48 mo) after transplantation, were evaluated for lipid profile and renal function tests.

Results: Hyperlipidemia has high prevalence in our patients both pre and posttransplantation and hypercholesterolemia and increased LDL had significant correlation with chronic allograft nephropathy (p=0.009) and P=0.025 respectively. Conclusion: In pediatric patient as in adults hyperlipidemia and particularly hypercholesterolemia has significant correlation with chronic allograft nephropathy and as adults may need specific therapy. Results: Pre-transplantation renal replacement therapy time ranged from 0 to 132 months. Eleven children underwent pre-emptiverenal transplantation. 43/72 transplants were from living related donors. Donor age ranged from 0 days to 74 years. 9 grafts were from donors <1 year of age and 5 of these grafts were transplanted en-block. HLA mismatches ranged from 0 to 5 antigens. Primary disease was: focal segmental glomerulosclerosis in 9, rapidly progressive glomeluronephritis in 6, reflux nephropathy in 23, nephronophthisis in 9, IgA nephropathy in 1, congenital nephrotic syndrome in 2, dysplasia-hypoplasia in 11, idiopathic membranous glomerulonephritis in 1, Henoch-Schönlein purpura in 1, hemolytic-uremic syndrome in 1, nephroblastoma in 1, polycystic kidney disease in 1 and of unknown origin in 4 children. Patient survival at five years was 97%. Allograft survival with living related transplants at one, two and five years was 95%, 95% and 82% respectively and with cadaveric transplants at the same periods was 86%, 86% and 86% respectively (p<0.05). Regarding en-block grafts, they functioned immediately and satisfactory and presented excellent graft function 10 years later. Most kidneys were lost due to acute or chronic rejection (n=6). Other causes were renal artery thrombosis (n=3), infections (n=2), withdrawal of immunosupressive regime (n=1). Conclusions: Results of this single center series of pediatric renal transplants are encouraging from the standpoint of patient and allograft survival. Conclusion: In infants with HN, the incidence of UTI was higher especially in those with OU, HN of higher SFU grade or HUN. The antibiotic prophylaxis may be recommended during 1 year after birth in infant with HN because the incidence of UTI was high in these period. Results: The underlying diseases were: sepsis with MODS (26.8%), septic shock (11.3%), severe intoxication (15.5%), trauma with SIRS (11.3%), drowning (2.8%), abdominal compartment syndrom (2.8%) and inborn metabolic disorders (2.8%). 43 children (61%) had acute renal failure, 28 (39%) patients met non-renal CRRT criteria. CVVH was performed in 39 (55%) children, CVVHDF in 32 (45%) children. CRRT duration was 6 to 216 hours (median 177.6 hours).

Dynamics of blood urea, creatinine, C-reactive proteine (CRP) and white blood cells (WBC) were evaluated. Significant decline (p<0.001) of creatinine along the treatment with CVVH as well as during CVVHDF was observed. Blood urea levels showed significant decrease only in children treated with CVVHDF (p<0.05). Significant decrease of WBC and CRP was observed only using CVVH. 37 children from the study group survived (overall mortality 47.9%). In non-survivors was time from CRRT initiation to its termination compared to time interval from CRRT initiation to the death of children with 3-4 organs failure significant (p<0.05) where as in non-survivors with 1-2 failured organs it was not. Conclusion: CVVH is efficient at removing urea and creatinine as well as inflammatory mediators (CRP, WBC). CVVHDF is more potent to blood urea elimination. Authors suggest preferring CVVH to CVVHDF in critically ill children to affect basic inflammatory parameters. To analyse HD and PD prescription (Pr) adopted in chronic dialysis children, were viewed data of 147 PD regimens in 91 patients (0.5-18years) and 100 HD regimes in 74 patients (age 1.8-18 years) treated in 12 pediatric centres in 2005. PD patients were on automated PD: -nightly intermittent PD (NIPD; 89 Pr): 9.6±1.3 (8-13) hrs; 13.3±5.5 (6-27) cycles/night; dwell volume (DV) 889±232 (465-1400) ml/m 2 BSA; -tidal PD (42 Pr): 9.7±1.9 (8-18) hrs; 16.9±5.6 (9-31) cycles/night; DV 1008±182 (600-1200) ml/m 2 ; tidal volume 63.8±9.5 (50-85)%; -continuous cycling PD (CCPD;16 Pr): 10.3±1.6 (8-14) hrs; 15.6±5.6 (7-27) cycles/night; DV 1017±162 (600-1280) ml/m 2 ; daytime DV 62±18 (50-100)% of night DV. In 27% of Pr dialysis fluid (DF) glucose concentration was >1.36%, and in 12% buffer was bicarbonate. DF of daytime dwell was 1.36% glucose (13 Pr) or icodextrin (12 Pr). Patients with residual diuresis were 63.5% of those on NIPD, 56% on tidal PD, and 6.2% on CCPD. HD was performed as bicarbonate HD (79%), hemodial filtration (15%) and acetate-free biofiltration(6%). Patients received 3 sessions/week in 66% of cases, 4/week in 23%, and 2/week in 9% of cases; 2 oxalosis patients were on daily HD. Session duration was 3 hrs in 44 Pr, 4 hrs in 36, and 3.5 hrs in17. Dialyser membrane was: polysulfone (38%); hemophane (19%); polyamide S (16%); cellulose acetate (9%); polyacrylonitrile (5%); cellulosediacetate (4%); cellulose triacetate (4%); polymethylmetacrylate (4%); polyether/carbonate (1%). Ratio between dialyser surface area and patient BSA was 1.05±0.19 (0.70-1.43) and was 1-1.20 in 31%, 0.8-1 in 23%, >1.20 in 12%, and <0.8 in 7% of cases. Isoniazid (INH) is widely used in most prophylactic and therapeutic anti-tuberculosis regimens because of its effectiveness and low cost. Acute intoxication by isoniazid is known to cause symptoms of seizures, metabolic acidosis, coma, and even death. We present a case of acute isoniazid poisoning in a seven years old patient who ingested 7 tablets (2100 mg) of isoniazid. She was admitted unconscious, with ventilatory insufficiency and convulsions. Renal and liver function tests were in normal ranges. She was intubated and mechanically ventilated. Despite parenteral midazolamand pyridoxine (vitamine B6) treatments convulsions went on. Then hemodialysis was performed and after hemodialysis convulsions and ventilatory insufficiency were disappeared and the patient was conscious and she was extubated. Hemodialysis may be an effective treatment alternative for the patients who doesn't respond pyridoxine treatment. The aim of this study is to analyse children under two years of age, with their first febrile urinary tract infection (UTI), identifying bacteriological etiology, antimicrobial resistance, urologicalabnormalities and renal damage. This is a prospective study including 92 children (63% girls) with their first febrile UTI. Mean age was 6 months (3-10), 27 (29%) patients were younger than 3 months (62% of them were boys). Urine was obtained by suprapubic aspiration (65.2%) or transurethral catheterization (34.8%). 37% had positive nitrite on urinalysis and 95.6% had leukocyturia. They were submitted to ultrasonography (USG), DMSA scan (within 4 months) and voiding cystourethrography (VCUG). The most frequent microorganism found in urine culture was Escherichia coli, (94.6%). In this study high bacterial resistance to antimicrobials was observed in relation to the following antibiotics: ampicillin (57.6%), first generation cephalosporyn (32.6%), sulfamethoxazole/ trimethopin (43.5%). Resistance to second generation cephalosporyn, aminoglycoside, nitrofurantoin and nalidixic acid was lower than 3.5%. Renal ultrasound was abnormal in 43.5% of the infants. Vesico-ureteral reflux (VUR) was observed in 34.7%, although only 7.6% had VUR grade III or more. The DMSA scan showed that 23 (25%) patients had renal parenchymal damage. Fourteen of these (60.9%) had normal ESR. There were 8 (8.7%) reinfections within a 6 months period, even under prophylactic treatment, and the presence of VUR grade III or more was the only one with a significant relationship. Conclusion: There were high levels of bacterial resistance to frequent used antimicrobials. This finding points toward a need for reviewing criteria of choosing initial blind therapy. Investigation with DMSA scan is important in the detection of renal parenchymal scars, irrespective of the reflux grade. Purpose: Urinary tract infection (UTI) has a risk of renal damage and is associated with VUR. VUR is investigated only by VCU. However, VCU is an invasive, painful study and many patients hesitate to be taken the study. We studied the correlation of VUR in VCU and defect of DMSA scan and investigated the possibility of substitution of VCU by DMSA scan. Material and Methods: From 1999 to 2006, the medical records were searched for children admitted to Cheongju St.Mary's hospital with the first UTI who had been evaluated with both DMSA scan and VCU within 1 months of the infection. The value of several clinical signs, laboratory findings, the resultsof DMSA scan and VCU were investigated. Bacteriuria was defined as 100,000 or greater colony-forming units in urine from a bag, midstream or catheter sample. Results: There were 54 patients underwent both studied at the first UTI. Mean age of the patients was 13 months old. The male patients were 38 (70%). The VUR was found in 19 of the 54 patients (35%), grade I-II in 5 and grade III-V in 14 patients. There was no significant correlation with the presence of VUR in sex, fever duration, blood white cell count and the level of serum creactive protein (CRP). But the patients with VUR grade III-V were significantly older than the patients with grade I-II reflux or without VUR. There were abnormal DMSA scan findings in 22 of 54 (41%). Of these patients, 11 were without VUR, 1 with VUR grade I-II and 10 with VUR grade III-V. The abnormal DMSA scan was correlated with the presence and severity of VUR. But VUR was found in 25% of patients with normal DMSA scan.

Conclusions: Abnormal DMSA scan is correlated with the presence of VUR, so the patients with abnormal DMSA scan require VCU. In order to prevent missing a quarter of patients with VUR shown normal DMSA, VCU should be recommended in all children with first febrile UTI. Cuba is the largest of the Carribean Islands with its 11,5 millions inhabitants. Cuba is considered as a developing country and is classified in the group of: "Lower Middle Income Countries and Territories". Despite low financial resources, Cuba has succeeded to develop an efficacious health care system with comparable results to those of West Europe and USA (WHO data) Ccl: 1) HD is the most prominent form of pediatric dialysis (automated night PD is in progress); 2) the No of transplantations is relatively low because of no participation to an international transplantation network; 3) high No of pediatric nephrologists; 4) high quality of patients care. Background: Inborn errors of metabolism in neonates are often characterised by hyperammonaemic coma within the first days of life and require prompt diagnosis and specific treatment such as toxin removal and nutritional support. CVVHD seems to be the optimal modality for extracorporal ammonium detoxification, however, little experience with small numbers of children has been accumulated. Patients and methods: From 1996 to 2007, 21 patients with hyperammonaemia (16 male, 5 female) were admitted for dialysis treatment: 18 neonates (mean age 3.8±2.4 days, range 1-10 days) with a mean birth weight of 3430±1023g and 3 infants (mean age 5.6±4.6 years, range 3 to 11 years). In 14 neonates and 2 infants we inserted venous double lumen Shaldon catheters (predominately femoral or jugular vein) for CVVHD treatment while 4 neonates and 1 infant underwent CAPD treatment.

Results: Plasma ammonia levels (range 508-7267 μg/dl before dialysis and 27-3317 μg/dl after dialysis) were reduced by 50% within 4.5±2.7 h by CVVHD and within 18.7±9.2 h by CAPD (p<0.05). Total dialysis time was 35.9±25.7h for CVVHD patients. No major mechanical complications were observed with CVVHD and stable blood flows (10-40 ml/min) and dialysate flows (1000-3000 ml/m 2 /h) were achieved. Due to severity of underlying disease, 2 out of 14 neonates (14%) undergoing CVVHD died on day 2-3 while 2 out of 4 neonatal CAPD patients (50%) died on day 3 and one infant patient died after 498 days of CAPD treatment. Twelve out of 14 neonates (86%) survived with no or moderate mental retardation. Conclusions: CVVHD is an effective modality to eliminate plasma ammonia within few hours. However, vascular access and blood flows are critical restrictions. Mental retardation has to be evaluated in larger scale studies.

R. Vilalta, E. Lara, A. Madrid, S. Chocron, J. Nieto Hospital Materno-Infantil Vall de Hebron, Nefrologia Pediatrica, Barcelona, Spain Background: Transplant nephropathy is the main cause of renal failure in kidney transplanted children. Until this situation is proved by biopsy, sometimes the progressive raise of creatinine leads to raise the anticalcineurinic (CNI) drugs with added nephrotoxicity. Sirolimus (SIR) plus an anticalcineurinicin less dose and mycophenolate (MMF) could offer in kidney-transplanted children an immunosuppressive regime with less toxicity and even an improvement of renal function. Methods and patients: 12 paediatric kidney-transplanted patients developed biopsy-proved chronic allograft nephropathy (age 6-19 y, mean 8) a follow-up post-transplant of 6 y and 7 exhibit also tubular involvement and acute CNI toxicity. SIR was added in all patients as a rescue therapy at 0.08 mg/kg/d. Results: After a follow-up period of 18 months, creatinine level diminished (p<0.04) in 8 patients (4 in group TAC, 3 in group CYA, with no significant differences). Creatinine level did not show a significant change in the other 4 patients (2 group TAC, 3 group CYA, basal creatinine 2.8 mg/dl. Serum cholesterol changed from 230±30 mg/100 ml to 223±2 (NS) and serum tryglicerides from 110±32 mg/100 ml to 121±24 (NS). Proteinuria also did not show changes (24±8 to 22±4 mg/m 2 /h (NS).

Conclusions: A poly-drug approach with less dose of anticalcineurinic added to the antiproliferative effect of sirolimus and the inhibition of purine synthesis based on mycophenolate mofetil could suppose an improvement of the renal function in children graft nephropathy an even in the graft survival. Steroids have been a cornerstone in renal transplant immunosuppression. Several strategies have been used to minimize their side effects. New immunosuppressive drugs have allowed steroid withdrawal or total avoidance. Aim: To evaluate a new protocol with steroid-free maintenance immunosuppression in pediatric renal transplant. Patients and methods: A prospective, non-randomized study in 46 consecutive first renal allograft recipients, followed-up to 24 months. Patients received prednisone the first 6 days, two-dose basiliximab induction and maintenance therapy with tacrolimus (TAC) and mycophenolate mofetil (MMF). No steroids were given after 6 d posttransplant. Controls were 20 historical-matched steroid-based children receiving basiliximab, TAC and MMF. All patients gave informed consent. Anthropometric, biochemical variables, acute rejection and CMV infection were compared using Student-t test and regression analysis.

Results: A better growth pattern was seen in steroid-free maintenance group reaching a normal growth at 24 months. GFR and serum glucose were similar in both groups. Total cholesterol levels were significantly lower in the study group. The incidence of acute rejection was 4.3% in steroidfree maintenance vs 8.6% in steroid-based group, no differences in CMV infection and blood pressure were observed. Hematocrit levels were lower during the first months after transplant in the steroid-free group, increased after 6 months post-transplant. Patient and graft survival was 98% at two-yr post transplant in the two groups.

Conclusions: This steroid-free maintenance immunosuppressive protocol was efficacious, safe, with a lower incidence of acute rejection, not increased risk of infection, preserving optimal growth, renal function and reducing cardiovascular risk factors. Objectives of study: To evaluate the lipid profile and its possible implications in children with end stage renal disease (ESRD) or renal transplantation. Methods: 19 children (11 boys, 8 girls) aged from 3.5 to 18 years, 9 on peritoneal dialysis (group I) and 10 with renal transplantation (group II) were studied. In all children were examined: serum creatinine, total cholesterol, triglycerides, high density lipoproteins (HDL) and low density lipoproteins (LDL). A cardiac and liver ultrasonography were also performed. The body mass index (BMI) and blood pressure were evaluated in all children. 13/19 children received also a triplex carotid study.

The median values of blood creatinine, cholesterol, triglycerides, HDL, LDL as well as the number of children with BMI over 95 th percentile in both groups were shown in Table I . All children had normal findings in triplex carotid study. Cardiac ultrasonography was abnormal in 1 child of group I and in 2 children of group II. Only 1 child presented lipoid invasion in liver ultrasound. 3/9 children of group I and 6/10 children of group II presented hypertension, well controlled, with antihypertensive therapy. Conclusions: Frequent evaluation of lipid profile is recommended in all children with ESRD or renal transplantation independently their BMI. In our study, children with renal transplantation presented better lipid profile compared with children on peritoneal dialysis. Group I with <18 months (n=14; 7,8±4,9 months) and Group II >18 months (n=7; 36,8±19,9 months). Results: Serum albumin, serum lipids values and the distribution of the categories of the peritoneal membrane did not present significant differences between the groups. Hypertension, Renal Residual Function (p=0,005), the renal urea Kt/V (p=0,007) and the weekly renal Ccr (p=0,005) were significantly higher in Group I, while the weekly peritoneal Ccr (p=0,025) and the total weekly Ccr (p=0,037) were significantly higher in Group II. Catch-up was not observed in any group. Control of the cholesterolemia, trigliceridemia and albuminemia were maintained with the dialysis time in both groups.

The goals of adequacy of the DOQI for Kt/V and Ccr were gotten respectively in 85,71% and 64,29% of the Group I and in 71,43% and 42,86% of the Group II. The longer time in dialysis was associated with the lowest values of Renal Residual Function, renal Kt/V and renal Ccr. The capacity of transport of the membrane was similar in both groups. Objectives of study: To explore the characterize of peritoneal transport in Chinese children with chronic peritoneal dialysis. Methords: PET was carried out 10 times for six children (mean ages 9.3±4.4, aged from 2 to 14 years) who were maintained by CAPD, and the infusion volume of dialysate was 1195±597 ml (1100ml/m 2 ). The peritoneal solution transport rate was evaluated by the standards of Twardowski's and PPDSC's criteria.

Results: In our study, the initial PET was performed at 38.7±15.6 days following initiation of PD, the 4-hours of peritoneal creatinine clearance (4h-D/P) and glucose absorption (4h-D/D0) was 0.85±0.24 and 0.34±0.19, respectively. According to the standards of Twardowski's and PPDSC 's criteria, the peritoneal transport categories were divided into high transport (H) (6/10), high average transport (HA) (1/10), low average (LA) (3/10) for peritoneal solution transport, and H (3/10), HA (4/10), LA (1/10), low transport (2/10) for glucose absorption. No low transport type of solution was uesd in our patients. The coincidence rate of peritoneal creatinine and glucose transport types were 100% and 90% between the Twardowski's and PPDSC's criteria, respectively. The different changes of peritoneal transport type were found in two patients with continuous PET. The value of 4h-D/P increased after peritonitis episodes.

Our results showed that the PET in 70% of CAPD children fall into high and high average transport categories elevated by PPDSC's and adult standards. The peritoneal solute clearance was adequacy in the children, but net water ultrafiltration was lower. Standard pediatric PET and its criterie are consistent with the adult criteria. The capability of peritoneal solute transport increased after peritonitis episodes. Verapamil (VP) is known to alter cyclosporine (CsA) bioavailability. The impact on immunoregulators (IL-2, TGF-β 1 , and TGF-β 2 ) in allograft recipients remains unresolved. A prospective open study to examine the impact of VP on peripheral blood cell mRNA encoding IL-2, TGF-β 1 , and TGF-β 2 and serum IL-2, TGF-β 1 , TGF-β 2 protein levels was performed. Parental written informed consent was obtained in all cases. Children with stable renal allograft function (<6 months), and receiving immunosuppression (CsA, PDN, either with AZA or MMF) were included. In the first visit, a clinical examination, two-point (2 and 12h) CsA pharmacokinetic profile, serum creatinine, serum for IL-2, TGF-β 1 , and TGF-β 2 protein levels (by ELISA) were obtained; peripheral mononuclear cells were collected for measurement of transcripts for 18s rRNA (house keeping gene) and mRNA for IL-2, TGF-β 1 , and TGF-β 2 (by real time quantitative PCR assay). After the visit one, patients were either withdrawn of VP (if the subject was already receiving VP) or started on VP 2mg/kg/day (if the subject was not receiving VP). Two weeks after, a repeat clinical evaluation and blood collection, as in the first visit, were performed. 21 pediatric recipients of renal allografts were included (17 were from LD, mean post-transplant time 4.8 years, mean CsA dose 3.8 mg/kg/day). The C2h and calculated AUC 0-12h were significantly higher in those receiving VP, but there was no difference in CsA trough levels. Protein and mRNA levels of IL-2 TGF-β 1 , and TGF-β 2 were not different. were previously seen by a nephrologist. Logistic regression was performed on anemia (Hgb<11.0 g/dl) and showed relative risk in blacks was 3.74 vs. whites. Relative risk in those who did not receive EPO was 2.77 vs. those who did. Of 19 black patients, 16 were anemic and 9 previously seen by a nephrologist. Of 55 white patients, 32 were anemic and 16 previously seen by a nephrologist. In summary, blacks and patients not receiving EPO at the time of dialysis initation were more likely to be anemic. Despite being seen previously by a nephrologist, nearly 60% of patients were anemic when starting dialysis. Further analysis is needed to determine causality to improve anemia control in incident dialysis patients. 2 of the AVF were in whites with 1 in a black patient. The AVG was in a black patient, with a CVC distribution of 20 whites and 11 blacks. 21 patients with CVC had been previously followed by a nephrologist and of these 12 had been followed for >6 months.

In summary, incident pediatric hemodialysis patients are primarily having CVC as initial access type. With 56.7% having been previously seen by a nephrologist and 57% of these for greater than 6 months, the reasons behind not having an AVF or AVG as primary access need to be explored and improved upon. This high incident CVC use is consistent with data reported in the United States, but not with other European and Asian countries. An effort to have a permanent AVF or AVG in incident pediatric hemodialysis patients needs to be made by the patient's nephrologist. To find the preventive measures for recurrent UTI in infants with first febrile UTI and normal urinary tract (UT), the incidence of recurrent UTI and its risk factors were investigated. Method: From June, 2002 to June, 2005 under 12 months of age (-6 mon: 152, 6-12 mon: 38), who were diagnosed as the first febrile UTI and proved to have normal UT, were enrolled to the retrospective study. For all infants with nonretractile prepuce, topical application of hydrocortisone for 2-4 weeks and physiotherapy was recommended. During the following 1 year, the incidence of recurrent UTI and the well-known risk factors such as female, young age, phimosis, vaginal reflux, and initial 99mTc-DMSA(+) pyelonephritis were evaluated. Result: The incidence of recurrent UTI in infants with normal UT was 21.1% and recurrent UTI episode was 0.23/patient-year. The recurrent incidence in male infants was 22.8%, which was not significantly different from 12.5% in female infants (P=0.193). The recurrent incidence in younger infants was significantly higher than in older infants [-6 mon: 25.0%, 6-12 mon: 5.3%, P=0.008]. This age-related difference was significant in male infants [-6 mon: 25.8%, 6-12 mon: 7.7%, P=0.045], but not in female infants (P=0.169). In infants with persistent nonretractile prepuces, recurrent UTI developed in 34.3%, which was higher than 15.6% in infants with retractile prepuces (P=0.041). The presence of the vaginal reflux (P=0.087) or initial 99mTc-DMSA(+) pyelonephritis (P=0.041) showed no significant difference in the incidence of recurrent UTI. Conclusion: In UTI infants with normal UT, younger infants under 6 months of age and nonretractile prepuces of male infants were the risk factors for recurrent UTI. Objective: Vascular endothelial growth factor (VEGF) appears to play a central role in the process leading to peritoneal angionesis and increased level of VEGF may conrtibute to high peritoneal small-solute transport rate (PTSR) in continuous ambulatory peritoneal dialysis (CAPD) patients in adult. VEGF-C is related to lymphogenesis, but its role in peritoneal solute transport rate is not known. In this study, we evaluated possible relationship between dialysate VEGF and VEGF-C levels and PSTR in children.

Method: Twelve children with no apparent inflammation process or disease, who had been on CAPD, were enrolled. Standard peritoneal equilibration test (PET) was done to evaluate PSTR. D/Pcreat and D/D 0 gluc were calcualted at 4hr of PET. Overnight dialysate levels of VEGF and VEGF-C were measured using commercial ELISA kit. Correlation between dialysateVEGF (or VEFG-C) and D/Pcreat (D/D 0 glu) was analyzed.

Results: Mean peritoneal dialysis duration was 9.25±7.18 months. Mean overnight dialysate VEGF and VEGF-C level were 44.74±30.49 pg/ml and 119.6±78.26 pg/ml, respectively. A significant correlation was noted between the dialysate VEGF-C and VEGF level (r=0.809, P=0.001). Dialysate VEGF level had negative correlation with D/D 0 glu of 4hr PET (r=-0.691, P=0.009). VEGF-C had no correlation with D/D 0 glu or D/P creat. Conclusion: There was significant relationship between dialysate VEGF and VEGF-C levels in children and significant correlation was also noted between dialysate VEGF and PTSR. It seems that VEGF contribute to high PTSR also in children on CAPD.

M. Feldkötter, L. Stapenhorst, B. Beck, U. Bangen, B. Hoppe

We currently use sirolimus as a second line medication in transplanted patients with a distinct nephrotoxicity of calcineurin-inhibitors. As our short term experiences were not as positive as expected, we performed a short term meta-analysis in our renal transplant recipients under sirolimus treatment:

We give an account of seven kidney transplant patients who were either directly started or were switched to a medication with sirolimus during September 2004 to February 2006. The reasons for this action taken were calcineurin-inhibitor side effects like severe arteriolopathy with lossof GFR, atypical haemolytic-uraemic-syndrome, seizures after the first dosages of CyA and a tacrolimus induced exanthema. In four of seven patients switched to sirolimus we observed severe side effects, exaggerating those of the calcineurin-inhibitor and hence, in three patients the latter treatment was installed again. Findings were distinct proteinuria in two patients, hyperlipidemia in three patients, wound healing disorders and, most strikingly, treatment resistant severe pancytopenia in one patient and severe interstitial pulmonary fibrosis in another patient, both with amelioration after termination of the medication, but still the need of oxygen therapy in the latter patient. In addition we noticed a slightly faster reduction of the GFR calculated with the Schwartz formula in five patients compared to the previous immunosuppressive regimen. Based on these findings we strongly feel that a more critical discussion of each case is necessary before changing the immunosuppressive medication. Also, the question arises on whether sirolimus can really be valued as an equivalent alternative to a calcineurin-inhibitor based immunosuppressive regimen in pediatric kidney transplantation.

Y. Kovalski, R. Cleper, I. Krause, M. Davidovits Schneider Children's Medical Center of Israel, Nephrology and Dialysis Unit, Petah Tiqwa, Israel Background: Despite significant technical improvements, haemodialysis in infants with end-stage renal disease (ESRD) is still associated with significant morbidity and mortality. Methods: The files of patients weighing less than 15 kg with ESRD who were treated with haemodialysis at our institute between 1995 and 2005 were reviewed for background and treatment characteristics, morbidity and outcome.

Results: The study group included 11 patients aged 7-75 months (mean 34.2 months) weighing 7.2-14.9 kg (mean 10.9 kg). Mean duration of dialysis was 11.3 months. Vascular access posed the major problem. Ten patients were dialysed through a central venous cuffed catheter and one through an arteriovenous fistula. An average of three different vascular accesses was required per patient (range 1-9). Mechanical difficulties were the most common cause of central line removal (56.5%), followed by infections (15.6%). Major complications causing significant morbidity were intradialytic haemodynamic instability, hyperkalemia, coagulation within the dialysis set, anaemia, hypertension, inadequate fluid removal and recurrent hospitalisations. Analysis of outcome revealed that 8 patients underwent successful transplantation, one returned for haemodialysis after 4.5 years due to graft failure, and 2 died. Conclusion: Haemodialysis is a suitable option for low-weight paediatric patients with ESRD awaiting transplantation, when performed in highly qualified centers.

The Importance of Antibiotic Prophylaxis in Management of VUR Vesicoureteral reflux (VUR) cause urinary tract infection (UTI) and renal scarring is a common condition in children. The detection and treatment of VUR before renal scarring is vital. Recently, optimal management of low grade VUR is controversial. The aim was to explore the kidney outcome in a cohort of patients with VUR. The patients were divided into five subgroups according to VUR grades. All of them were treated with low dose prophylactic antibiotics until the age of 5 years. Urine culture was repeated monthly. Background: Anemia is a common complication in patients on hemodialysis. Treatment of anemia with recombinant human erythropoietin (rHuEPO) may lead to iron deficiency. Intravenous sodium ferric gluconate complex (SFGC) therapy improves iron stores. Objectives of study: Aim of our study was to assess effects of maintenance sodium ferric gluconate therapy in pediatric patients on hemodialysis on mean hemoglobin (Hb), hematocrit (HCT), transferrin saturation (TSAT), serum ferritin and rHuEPO dose, as well as safety of therapy with SFGC. Methods: Intravenous SFGC therapy was administered for 3 months in mean dose of 1.2 mg/kg/week to eight pediatric patients on hemodialysis. Patients were from 2 to 16 years old (4 males and 4 females, aged 11.5±5 years). All patients were prescribed rHuEPO before start of study.

Results: SFGC therapy was successful in maintenance of mean Hb (increased from 10.5 to 11.3 g/dl), mean HCT (improved from 31% to 33%), mean TSAT (from 23 to 30%) and mean ferritin level (from 592 to 765 ng/ml). High ferritin levels in two patients were due to inflammatory disease rather than the sign of iron overload. The mean weekly rHuEPO dose decreased from 4380 to 3500 IU. No significant adverse event due to intravenous SFGC therapy occurred.

Conclusions: Intravenous maintenance SFGC use in pediatric patients on hemodialysis was safe and successful in maintenance of iron indices, thus allowing reduced use of rHuEPO.

The The viral hepatitis B still remains a serious problem, especially actual in patients with end-stage renal disease (ESRD) on renal replacement therapy (RRT). The high frequency of HBV infection transmission in hemodialysis units and immunodeficiency modify hepatitis clinical course and outcomes and worsening vaccination results and renal graft survival. We have analyzed the results and influence on transmission of HB -infection of hepatitis B vaccination in 28 children aged from 6 to 17 years with ESRD on chronic hemodialysis. Majority of children were boys (53.5%) older than 11 years (85.7%). An assessment of HBs-Ag has been conducted prior and during the vaccination (EngerixB) by scheme 0-1-6 months. After first vaccination HBV infection was detected there after in 10.7% of children, after second vaccination in 7.1%. In all patients (11) which have received three tours of vaccination, an active immune response was developed. Thus, vaccination against viral hepatitis B is effective and prevents HBV infection in children with end stage renal disease on chronic hemodialysis. Renal transplantation (Tx) represents the best treatment for the patient with CRF. Scientific advance has been able to optimize the immunosuppressive treatment however the adherence to treatment has been not maintained. Aims: To identify the factors that influence in non-adherent behavior with the purpose of designing effective educational strategies. Methods: The qualitative focus was carried out through patients and tutors interviews. The quantitative aspect applies for epidemic variables, time post-Tx, percentages and frequency of the sentences coming from the analysis of the interviews. Nurse, psychologist and a social worker were incorporated with the purpose of elaborating an instrument based on seven questions related to the transplantation, risk and/or loss of the graft; besides the events happened as consequence of this, allowing that interviewed manifested with freedom their opinions. The interview was recorded in a microcassette and later transcribed. Analysis was determined by categories containing the answers of each question granting the agreement sentences according to the frequency which was repeated in each interview. Informed consent was obtained. Results: 150 Tx (1989 -2006 ; 15 non-adherent, 80% of them were interviewed. Mean age: 9.7 ys. Loss the graft: 50%, time post-Tx: 37.7 months, DD: 67% LD: 33%. The lack of supervision in the taking of medications, numbers/schedules medications, family conflicts and the poor communication with the parents/medical team seem to be the main factors for non-adherence. Conclusion: It is necessary to modify the pattern of the patient's attention transplanted under the pattern of chronic suffering that allows the sick person's and their family active incorporation to the process in an integral way to the multidisciplinary group.

Infantile Results: 9 patients (4 females, 5 males) <15 kg, 6/9-<10kg at PD start were treated. They consisted 20% of our center's PD patients (43 pts). Age at PD start: 21.6±16 months (median 17), 8/9 pts <24 mo. PD therapy duration: 4-21 mo (median 6), 3 pts >12 mo. ESRF cause: congenital nephrotic syndrome 4 pts, dysplastic kidneys 4, cortical necrosis 1. 6 pts were fed by gastrostomy, 4 pts received GH (growth hormone). 5/9 pts had hypertension (HT) treated with >2 drugs and 1-4 CV events. PD type: 5/9 cycler-assisted, 1/9 CAPD (continuous ambulatory PD), 3/9 both. PD adequacy targets (KT/V>2.5) were reached in 8/9. Peritonitis: 0.22 episodes/patient-month, 3 pts had >3 episodes. 6/9 pts had >2 PD catheters and 5/9 >5 PD-related surgery. Outcome: 6/9-kidney transplantation, 3/9 switched to HD for infections or uncontrolled HT. Height ±SDS median 0, weight ±SDS median +1.1.

Conclusions: Small infants with ESRF can be successfully treated by PD despite high rate of infectious, CV and surgical complications. PD therapy main target is optimal growth towards kidney transplantation.

Hyperlipidemia is a well recognised complication of renal transplantation. It is a fairly common problem in the paediatric renal transplant population. Its prevalence ranges from 16% to 72% though the mechanism is not clear. Steroids, calcineurin inhibitors and rapamycin are the main culprits in inducing hyperlipidemia, which is a potential risk factor for cardiovascular heart disease and graft dysfunction. Long term effects of these immunosuppressive drugs in children have not been adequately studied. Of the calcineurin inhibitors Cyclosporine (Csa) was found to induce hyperlipidemia compared to Tacrolimus (Tac). Post-ransplant hyperlipidemia is well described in adults; the same cannot be said in children. In adults, post-transplant hyperlipidemia increases risk of cardiovascular disease 3 to 4 fold. Screening and management of hyperlipidemia has therefore become an important part of current long term management of transplant patients.

There is a limited data on prevalence of hyperlipidemia in renal transplant in children and even more so locally here in South Africa. Most of the known studies have been conducted in the first world, there was therefore need to determine prevalence locally. This information would ultimately assist in the overall management of our renal transplant recipients. Majority of the patients had normal lipid profile. 25% of the patients had high cholesterol levels, while 25% of the patients had high TG levels. 4/10 (40%) of the patients on Csa had hypercholesterolemia compared to only 1/11 (9%) on Tac (p=0.15). 2/10 (20%) of the patients on Csa had high TG compared to 3/11 (28%) on Tac (p=1.0). The study concluded that the prevalence of hypercholesterolemia and hypertriglyceridemia in renal transplant pts is high, comparable to other studies and that there is a tendency towards having more lipid abnormalities in transplant pts on Csa. Grade 3 VUR in 24 (39%) and . The incidence of abnormal findings was significantly higher in children with UTI and VUR than in those with UTI without VUR (88.5% vs 67%; P<0.05). In children with no VUR, Grades 1-2 VUR, Grade 3VUR and Grades 4-5 VUR, renal scarring rates were 67%, 70%, 90% and 88%, respectively. The patients with higher grades VUR tended to have more than 3 scars on their DMSA scans (P<0.01). Our findings suggest that renal scarring resulting from UTI is mostly related to VUR, but sometimes is caused by the infection itself. We can conclude that VCU is essential for diagnosis of VUR, but 99mTc-DMSA scan shouldn't be avoid in the management of children with UTI. [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] years. Seventythree (97.3%) of them were on triple immunosuppressive therapy, one on double therapy, and one didn't use any medication. Overall, 9 subjects (12%) had at least one episode of UTI. Twenty-four episodes of urinary tract infection occurred in 9 children: 7 episodes in two girls with neurogenic bladder (NGB), 9 episodes in two boys with posterior urethral valve (PUV), four episodes in an obese girl with Laurence-Moon-Biedl syndrome, 2 episode of UTI in 2 girl with unknown primary renal disease and 2 episodes in 2 girl, one with polycystic kidney disease and one nephronophthisis. Conclusion: UTI following kidney transplantation was more common in children with known lower urinary tract abnormalities. Key Words: urinary tract infection, kidney transplantation. Background: In Japan, the severe shortage of cadaveric kidneys led clinicians to attempt performing ABO-incompatible living kidney transplantation (Tx). Some reports demonstrate successful results of the combination of plasmapheresis (PP), strict immunosuppression and splenectomy. However, we should concern about a great risk of surgical invasion and postoperative serious infection in younger patients who underwent splenectomy. Recently, a few reports suggested anti-CD20 monoclonal antibody (rituximab) can be an alternative to splenectomy. Patient and Method: A 9 years old boy with bilateral hypoplastic kidneys had been treated with peritoneal dialysis for 3 years. Since his blood type O was incompatible with paternal blood type A, we arranged to perform Tx using PP and rituximab without splenectomy. A single PP was performed on days -10, -7, and -3 to reduce anti-A antibody (Ab) titer. Rituximab was administered in a single dose of 375 mg/m 2 on day -6. Basiliximab, tacrolimus, mycophenolate mofetil and methylprednisolone were used for immunosuppression. Results: Before Tx, the anti-A Ab titer was reduced from 1:32 to 1:8, and CD19 level was suppressed from 25% to 3%. Tx was performed without splenectomy and he had excellent initial graft function. We observed anti-A Ab titer rose up to 1:128 on day +5, but it decreased spontaneously to 1:16. There were no side effects and severe infections during the perioperative period, but the neutropenia treated by GCSF appeared 3 months after rituximab administration. The protocol biopsies were performed in 1 month and 6 months, which revealed no signs of rejection. Conclusions: ABO incompatible Tx using PP and rituximab without splenectomy can be a therapeutic option in children to avoid a invasive surgery and infectious risks. Further establishment of optimal protocol for children are necessary to obtain excellent outcomes safely. 1.70.2, 1.320.4, and 75.65.5, 66.415.1, in HIVAN, and OD, p=0.06, p=0 .08, respectively. Serum P levels were 6.71. 1, 4.60.9, and CaP were 54.517.0, and 39.68.7, in HIVAN and OD, p=0.044, p=0. The aim of this study is to identify the outcome of the physically or socially handicapped children with end stage renal disease (ESRD) receiving chronic peritoneal dialysis (CPD). Among 95 patients commenced on CPD, 11 handicapped children with ESRD receiving CPD were identified in our unit during the period between November 1995 and February 2007. Age at CPD initiation ranged from 5.5 to 15.5 years (median age: 11; 6 girls, 5 boys). Underlying diseases were neuropathic bladder and vesicoureteral reflux (in 3 patients), chronic pyelonephritis (in 3 patients), vesicoureteral reflux (in 2 patients), amyloidosis (in 2 patients), and Alport syndrome (in 1 patient). Causes of handicapped status against CPD were inadequacies of indoor resources (in 3 patients), cerebral palsy (in 2 patients), Down syndrome (in 1 patient), inadequate psychosocial status (in 1 patient), surgically corrected rectovesicale fistula and ectopic anus (in 1 patient), blindness (in 1 patient), ventriculoperitoneal shunt and paraplegia (in 1 patient), colostomy (in 1 patient). All catheters were implanted percutaneously by the same pediatric nephrologist. Median duration of dialysis was 24 (range 3-124) months. During a total of 443 dialysis months, 27 episodes of peritonitis (1 episode/16.4 patient-month), 1 episode of exit-site infection, and 1 episode of tunnel infection occurred in 8 of 11 children. Except for an inguinal hernia in 1 patient, we did not observe any mechanical complication related to catheter. CPD was terminated in 6 children (death in 3, renal transplantation in 2, switch to hemodialysis in 1). Before initiation of renal replacement therapy, some negative baseline factors may not be really contraindications for CPD. The socioeconomic and geographic factors greatly influence the prevalence and outcome of renal disease in children. The subspecialty of pediatric nephrology in Sudan was established few years ago and the facilities for the management of renal problems are limited. The aim of this study is to review the demographic profile, complications and outcome of CAPD after nineteen months of treatment. All children who underwent CAPD from June 2005 to January 2007 were studied. There were 22 children (12 males), the mean age was 11 years (range from 11 months to 16 years). The majority of children has undetermined cause of ESRD (11 children). The most common complication was peritonitis (peritonitis rate was 1/8.3 patient/months. 8 patients had refractory peritonitis that necessitate catheter removal, exit-site infection was documented in 4 children and catheter block in 4 children.

There were 12 drop out of the program 4 were due to deaths, 7 changed modality and one family withdraw treatment.

In conclusion this analysis has stimulated improvement in nurses training and supervision as well as attempts to improve catheter survival and microbiology monitoring.

The -5) , looking for symptoms of hypovolemia (cramps, abdominal pain or headache) during or at the end of HD treatment. Bioimpedance measurements were performed at the end of each session according to the 50 KHz tetrapolar technique; resistance and reactance values were plotted on the age and gender specific 50 th , 75 th and 95 th percentiles of the vector distribution in the healthy population (reference tolerance ellipses) as a resistance-reactance graph. Hypovolemia (HV) was indicated by a vector shifted to the upper pole, out of the 95% tolerance ellipse; normovolemia (NV) by a vector inside the 95° ellipse. Patients complained of one or more of the above-mentioned symptoms in 26% of HD sessions, while BIVA suggested HV in 47.9% of the sessions. Symptoms were significantly more common (p<0.05) in sessions with HV (20/57 cases; positive predictive value 35.1%) than in those with NV (11/62 cases; negative predictive value 82.3%). BIVA suggested HV in 20/31 sessions with symptoms (sensitivity 64.5%) and NV in 51/88 sessions without symptoms (specificity 58%). No significant differences in the accuracy of BIVA were found between patients either younger vs older than 18 years, or with height SDS <-2 vs >-2, or taking vs not taking antihypertensive drugs. In conclusion, BIVA can be useful in assessing dry weight in children and young adults on HD: since patients with a vector shifted to the upper pole, out of the reference 95% tolerance ellipse, are at high risk of hypovolemia during the next HD treatment, the increase of the dry weight is then indicated Chronic antibody-mediated rejection can occur as a de novo complication in renal allograft recipients and is associated with C4d deposition in peritubular capillaries in the renal graft and positive circulating anti-HLA antibodies, although the sensitivity and specificity of positive C4d staining for chronic humoral rejection requires further study. Renal outcome appears to be worse in C4d positive patients. Current treatment strategies to manage C4d-positive chronic humoral rejection are poorly defined. Various protocols with enlarged doses of tacrolimus, mycophenolate mofetil, plasmapheresis, IVIG and rituximab have been reported in adult patients. We investigated four pediatric patients (mean age 13.6 yrs; range 10 to 17 yrs) after renal transplantation that developed C4d positive chronic rejection. In 3 of 4 patients, maintenance immunosuppression with calcineurin inhibitors had previously been minimized because of severe toxicity. In 3 of 4 patients, an elevated anti HLA class II antibody titre could be detected; donorspecific antibodies were positive in 2 patients. All patients experienced a progressive deterioration of graft function. Treatment with repeated intravenous immunoglobulin (IVIG) (1 g/kg body weight per week over four consecutive weeks) followed by a single dose of rituximab (375 mg/m 2 ) was therefore initiated. Three of four patients showed an improvement of graft function with a mean increase of GFR by 25%. One patient with advanced chronic transplant nephropathy lost his graft after 6 months. This pilot study demonstrates that the combination of high-dose IVIG and rituximab can stabilize or improve transplant function in chronic antibody-mediated rejection without major side effects. The use of IVIG and rituximab appears to reduce the active immunologic process, but larger trials are needed to support these observations. Cardiovascular diseases are some of the most important causes of morbidity and mortality in children with end stage renal disease (ESRD). Chronic inflammation has been suggested to be a risk factor for cardiovascular diseases. The aim of this study was to investigate the relation between CRP and cardiac changes in children on hemodialysis. This study was conducted on 60 patients (30 patients were hypertensive & 30 were normotensive), 39 males (65%) and 21 females (35%) on regular hemodialysis due to ESRD. Their ages ranged from 7 to 16 years (mean 14.93±3.0). Sixty age-and sex-matched controls were also included. Significantly higher velocity of circumferential fibre shortening (VCFS), Tei index, interventricular septum thickness in diastole (IVSd), left ventricular mass index (LVMI) and isovolumetric relaxation time (IVRT) and significantly lower e/a ratio were found in all patients as well as in hypertensive & in normotensive groups as compared to the controls. Significantly higher IVSd and LVMI were found in hypertensive patients than normotensive patients. Significantly higher high sensitivity CRP (hs-CRP) & CRP latex were found in all patients as well as in hypertensive & in normotensive groups when compared to the controls. CRP was significantly higher in both study groups with CNS symptoms and cardiac symptoms in comparison to those without. It was also significantly higher in patients with increased LVMI & than in those with abnormal e/a ratio. HDLc showed a significantly direct negative effect on CRP. S. Ca 2+ , Se. P and Ca x P had a significantly direct positive effect on it. We can conclude that the cardiac affection in children with ESRD appears in the form of LV hypertrophy with early diastolic affection. CRP could be correlated to these changes and to CNS symptoms and cardiac symptoms in these patients.

IS. Lim, HS. Lee, DW. Kim, WH. Choi Chung-Ang University, Pediatrics, Seoul, South Korea Purpose: Urinary tract infections are common clinical problems occurring in infants and pediatric patient groups, most frequently caused by uropathogenic E. coli. Urinary pathogens almost always infect the host through ascension from the rectum, vagina to the urethra and bladder. Recurrent urinary tract infection is a disorder involving repeated or prolonged bacterial infection of the bladder or lower urinary tract. In this study, we examined the substitusion effect of probiotics in the high risk group of recurrent urinary tract infection.

Objectives & Methods: Patients diagnosed as recurrent urinary tract infection were administered probiotics for six months, and urine cultures were checked during the period. Probiotics in this study were selected among the products commercially saled in Korea, namely Lactobacillus acidophillus, Bacillus subtilis, and Bifidobacterium infantis. Single blind study was done for selection of probiotics for patients.

Result: The separated bacteria from the urinary tracts of the patients were the same as administered probiotics in some patients. Conclusion: In recurrent urinary tract infection, there seemed to be a substitution effect of probiotics for uropathogenic bacteria, and it is reasonable to administer probiotics for long period in the high risk group of recurrent urinary tract infection.

Renal Insufficiency Therapy in Children: Quality Assessment and Improvement: the RICH Q Study Objectives: Outcome studies in children on chronic renal replacement therapy (cRRT) have revealed a 30-time increased mortality and 40% co-morbidity in adult survivors. Information on the quality of care of treatment centers and on the impact of advised quality indicators on outcomes in children are lacking. No data exist on the impact on these outcomes of the different treatment modalities, peritoneal dialysis, hemodialysis & transplantation either. Until now, no structural corporation and consensus on general guidelines with respect to cRRT exist between the 9 Dutch (NL) and Belgium (B) centers for pediatric cRRT. Aim of the study: 1. Assessment of the current quality of treatment cRRT in children (QT) in NL & B and of the effect of recurrent peer review of the achieved outcomes on the QT. 2. The assessment of the effect of different treatment modalities on outcomes. 3. The creation of a format for multicenter trials.

Methods: All prevalent patients on chronic dialysis aged <19 years at onset of the study & all incident patients during the study period with onset of cRRT<19 years of age, from B & NL will be included. Treatment characteristics and quality indicators of cRRT with respect to physical and psychosocial outcomes will be collected of all patients. Operational data collection and management will be performed by members of the Dutch Institute for Quality Care in dialysis patients (Hans Mak Institute). Each 6 months, all data will be revealed and actively discussed by representatives of all centers (peer review). The effect of registration and peer review on the QT will be analyzed after 2 & 4 years. Comparison will be made between the effects of cumulative periods of different RRT models on outcomes. The study will be performed between August 2007 & 2011.

On estimation, 200 patients will be analyzed.

Renal Renal transplantation in patients with lower urinary tract dysfunction (LUTD) of different origin is a challenging issue in field of pediatric transplantation. We report our single centre experience to evaluate the patient and graft survival as well as risks of the surgery and immunosupressive therapy. Among 70 pediatric transplant patients 11 patients had severe lower urinary tract dysfunction. Videourodynamic test was performed in all patients preoperatively and postoperatively. The cause of urological disorders was secondary to neurogenic bladder (n: 5) and valve bladder (n: 6). Clean intermittent cathatetization (CIC) was needed in 6 patients to empty the bladder. Pretransplant augmentation ileocystoplasty was created in four patients and gastrocystoplasty in one patient to achieve low-pressure reservoir with adequate capacity. Three of the patients received kidneys from cadaveric and 9 of them from living donors. The mean age at transplantation was 15±4.7 years. The median duration of transplantation was 18 months (range 1-49 months). At their last visit median creatinin levels were 0.95 mg/dl (0.8-2.4) . Three patients had recurrent symptomatic urinary tract infections who had augmented bladder and on CIC. One of them had creatinine levels of 2.4 mg/dl. One patient with ileocystoplasty who developed urinary leak and ureteral stricture in early postoperative period was treated by antegrade J stent. Severe LUTD reserves high risks for graft kidney. However our data suggests that renal transplantation is safe and effective treatment modality if the underlying urologic disease properly managed during the whole course of transplantation period. Since surgery and follow-up of these patients is more complicated, patient compliance and experience of transplantation team will have significant impact on the outcome.

R. Meneses, L. Sylvestre, J. Sousa, D. Ribeiro Hospital Pequeno Principe, Pediatric Nephrology, Curitiba, Brazil Introduction: In July 2000, we started a systematic evaluation program of each patient on chronic PD. The aim of this study was to analyze the long-term outcome of children on PD program. Material and Methods: we evaluated all the patients on PD between July 2000 and May 2006, who performed 3 complete protocols, with a minimal interval of 6 months between them, consisting of: anthropometric measurements, blood pressure and cardiological status, standardized laboratorial evaluations, PET test, clearance and kT/v, measurement of the intra-peritoneal pressure (IPP), occurrence of infections, hernias or constipation and need to change the catheter. We then compared all the evaluations using the GraphPad Prism Software, a p value <0.05 was considered significant.

Results: 36 out of 74 patients were eligible, mean age 8±5 years old at the first evaluation, 61% boys, primary renal disease: 45% uropathies, 28% glomerulopathies, 8% tubulopathies and 19% other causes. There was an improvement on BMI and weight/height z-scores and worsening of height/age Z-score, but none was significant. There was also no significant decrease in residual renal function (p=0.51), adequacy parameters remained stable: Clearance (p=0.84) and kt/V (p=0.58). Most patients were converted from CAPD to CCPD and NIPD, and some had to increase daytime dwells (p=0.0098).Constipation and the number of infections improved but not significantly. Laboratorial evaluations, peritoneal membrane characteristics, IPP, need to change the catheter and occurrence of hernias did not change over the time.

Conclusion: A long-term maintenance of children in peritoneal dialysis program is possible, but reaching a satisfactory clinical condition is a great challenge. Several points need to be checked for planning a better adequacy and survival of dialysis technique in children waiting for a graft. A rigorous follow-up protocol seems helpful in precocity of prescription strategy modifications. We observed a stable long-term outcome observing these adequacy tools.

Outcome The recurrence of primary disease in transplants is a well-known problem. We report our single centre experience to assess the frequency of the recurrence of primary glomerulonephritis in children after renal transplantation. Medical reports after 1990 of 12 children with primary glomerular disease were evaluated. The 13 grafts were nine from living related and four from cadaveric donors. Eight of them were diagnosed as FSGS, 2 of them MPGN and 2 of them PAN. The mean age was 15.5±5.4 years. However the median transplantation duration was 47 months, one of the FSGS patient had hyperacute rejection. Five years later she had second graft with the serum creatinine 0.7 mg/dl at 7th year of second transplantation. And all recipients were immunosuppressed with either cyclosporin A or tacrolimus, azothioprine or MMF and steroid based regimens. Mutational analysis was available in two patients, they had homozygous podocin mutations. Post transplant recurrence of FSGS was confirmed in one patient. Glomerular tip lesion was the only histologic abnormality on graft biopsy. He has treated with plasmapheresis with no improvement of proteinuria. Two of the FSGS patients had thromboses after transplantation. One of them had cardiac thrombosis with heterozygote MTHFR mutation and one of them had renal artery thrombosis and loss of graft with prothrombin 20210A mutation. Both of them have had additional risk factors for thrombosis. They have all functioning grafts except one. We have not observed any recurrence in patients with PAN and MPGN. Although the number of our patients quite small, renal and patient survival seems to be more favourable in our experience but we strongly recommend the evaluation of all risk factors of thrombosis and give appropriate anticoagulation. Skin involvement in factor H deficiency (FHD) associated to hemolytic uremic syndrome (HUS) has never been reported. We describe the case of a young adult on regular hemodialysis (HD) for FHD-HUS who developed microangiopatic skin lesions and was successfully treated with plasma exchange (PE). The patient developed end stage renal disease secondary to FHD-HUS (SCR20) in 2004, when she was 32. After one year of HD she complained of severe night pain in the perimalleolar areas, followed by skin lesions which evolved into superficial ulcers (Fig1). In August 2005, due to the worsening of the skin lesions, the patient started HD and PE (2 litres of fresh frozen plasma per session twice a wk) based on the hypothesis that skin lesions were expression of thrombotic microangiopathy. After 7 wks of PE there was a skin improvement (Fig. 2) and a pain relief. PE was discontinued. 3 wks later she started to complain of the usual pain in the right foot. PE program combined to HD was restarted and the symptoms ceased again. PE was gradually discontinued and she was addressed to regular plasma infusion of 0.5 litre per wk. So far, after 18 months the pain and the skin lesions did not show up again.

M. Belingheri, S. Cristino, P. Basile, V. Bianchi, A. Leoni, S. Testa, L. Ghio, A. Edefonti, G. Ardissino Ospedale Maggiore Policlinico IRCCS, Mangiagalli e Regina Elena, Pediatric Nephrology, Milan, Italy Background: In rapidly growing children on hemodialysis (HD), the determination of dry weight still remains troublesome. Bioimpedance analysis (BIA) is potentially helpful in quantifying the fluid to be removed but its specific role, in routine clinical practice, is not yet clearly set. The aim of the present study was to test the feasibility of prescribing ultrafiltration (UF) exclusively based on BIA parameters. Methods: Differences in body weight, Resitance (Rx) and Reactance (X-C) between pre-and post-HD were calculated in order to derive the equivalence between UF and BIA parameters in a 3 years old girl over a period of 16 months. For 21 consecutive HD sessions, UF was prescribed exclusively based on the derived UF-BIA equivalence. This period was compared with 21 HD sessions where UF was prescribed by the conventional approach.

Results. Xc correlated with ultrafiltration better (r: .75) than Rx (r: .64). BIA-based compared with Weight-based UF prescription showed a significantly lower number of HD sessions complicated by hypotension (19% vs. 50%), need of fluid reinfusion (5% vs. 50%) and a better quality of the HD sessions (86% vs. 37%).

Conclusion. Prescription of UF solely based on Xc is feasible and provides a better outcome compared to the conventional modality of UF prescription. We believe that this approach could be useful for any patients with low tolerance to UF or with problems in setting the correct dry weight. Aim: The aim of the present prospective study was to determine the incidence of urinary tract infection (UTI) and related abnormalities in children ages between 0-2 years. Material and Methods: All children between 0-2 years old whose admitting to first step health offices (routine controls and immunization) was screened for UTI with urine dipstick test after education of minimum two persons from first step health offices according to protocol with two tertiary child care center and Health Directorate of Izmir Province in Turkey between July 2005 and July 2006. All patients with urine dipstick test abnormalities were referred to tertiary child care centers for evaluation. Urine microscopic evaluation and urine cultures and other further investigations were performed in tertiary care centers after obtaining urine with urinary catheterization.

Results: 14.918 children (55% boys) were screened with urine dipstick test. The children's mean age was 11.7±5.6 mo (median 10 mo). Screening test was found normal in 12.527 (84%) children. 962 of 2391 (40%) of referred child were admitted to tertiary care centers and evaluated for UTI. UTI was demonstrated in 419 children (2.8% of screened and 44% of evaluated children's). UTI incidence was found 4.1% in girls and 1.7% in boys. Urinary tract abnormalities were found in 24 children (0.2% of screened and 5.7% of evaluated children's). The most common urinary abnormality was vesicoureteral reflux (17 patients).

Conclusion: The UTI incidence was 2.8% in children ages between 0-2 years, UTI more common in girls than boys in this age group and only small group of children has urinary tract abnormality which is determined with routine urine screening. Knowledgement: Thank you for this opportunity to Health Directorate of Izmir Province. We describe DS post-PELDRT in 2 children with no known neurologic problems and discuss potential predisposing factors. A 12.2 kg girl with renal dysplasia was started on a calcineurin inhibitor (CNI) one week pre-T and when her blood urea nitrogen (BUN) was 110 mg/dl. On admission for T, the BUN had increased to 146, and her serum sodium (Na) was 142 mmol/l. Post-T, she remained intubated and paralyzed to permit generous volume supplementation, including 1: 1 replacement of her vigorous urine output (UOP), initially with 0.45% NaCl in water. Five hours post-T, her BUN was 17 and her Na 126. After modification of UOP replacement, her Na normalized. On the morning of post-T day 1, paralysis was discontinued, but she did not awaken and had sluggish pupillary reactions. Computed tomography of the head (CTH) revealed diffuse cerebral edema, and brain death occurred. A 39 kg adoloescent with polycystic kidneys was started on a CNI 4 days before PELDRT. His BUN and Na then were 76 and 142, respectively, and had not changed on the day of T. Post-T, the patient was immediately extubated. With UOP replacements as described above, his BUN and Na decreased from 74 to 12 and 143 to 124, respectively, over 24 hours despite adjustments in the Na content of his intravenous fluids based on urine Na levels. The patient then had a 10-second tonic-clonic seizure, followed by a 5-hour post-ictal state. CTH was negative, and the patient recovered completely. We conclude that DS, caused by a rapid decrease in serum BUN and thus osmolality, may complicate PELDRT in settings even with older pediatric recipients or without excessive elevation of pre-T BUN. Other factors contributing to this DS may include relatively mild hyponatremia and CNI effects on both pre-T uremia and seizure threshold. Results: 89 patients, predominantly males, ages between 5 months and 21 years old. The mean incidence of peritonitis was 0.1 episodes/patient months. Fifty-seven patients (64%) had at least one episode of peritonitis.There were 145 peritonitis, 85% percent from all episodes began at home, 35% caused by Gram negatives, 38% by Gram positives, 8% by fungus, 19% had a negative culture and in less than 1% it was not performed. The mean treatment time was 19 days, 45% had a good response to initial empiric antibiotics (cefazoline and amicacine). The interval between the beginning of dialysis and the first peritonitis episode varied from 1 to 1462 days, occurring in the first 6 months in 50% of the patients. Successful treatment occurred in 75% of the cases, 18% were transfered to hemodialysis, 7% had a consecutive peritonitis episode, and 1 patient died due to mesenteric artery trombosis. Conclusion: peritonitis occurred early in our patients. Even though most of them have a good initial response, there is still a great amount that have complications leading to technique failure. Continuous education for the patients and health team, aiming early diagnosis and treatment, are useful to preserve the technique and decrease morbidity and mortality associated to peritonitis.

D. Davis, J. Emancipator, X. Zhu, C. Rosen

Objective: To assess for SD in P chronic kidney disease (CKD) patients before and after RTx. Methods: We assessed 4 symptom (Sx) domains of sleep disorders: 1) sleep-disordered breathing (SDB); 2) insufficient sleep (IS) (shortened sleep time or nap); 3) excessive daytime sleepiness (EDS); and 4) restless leg syndrome (RLS) using a set of standardized questionnaires in 51 patients with CKD (age 5-18 yrs) including Non-D Non-Tx (NDNTx) (n=19), D (n=11), RTx (at least 3 months post-Tx) (n=21), and 15 age-matched sibling controls (C) without known CKD. The presence of an overall SD was defined by positive responses in any of the 4 Sx domains. Results: Mean age (SE) ranged from 11.9 (3.7) to 14.7 (3.8) in the 4 pt groups (p>0.05) without significant differences in gender, race, or congenital CKD. Estimated mean GFR (ml/min/1.73m 2 ) (SE) was significantly higher in the RTx group [75.8 (22.4) Methods: In a prospective design, 64 renal transplanted children, who had renal transplantation at least 3 months before, at Namazee Hospital, were enrolled in our study. Immunosuppressive regimen consisted of cyclosporine and prednisolone plus mycofenolat mofetil or azathropin. Data regarding GFR, serum creatinine, electrolytes, lipids and C 0 and C 2 levels was collected at beginning, in one-month, and five-month intervals. Cyclosporine was adjusted to 100-250 ng/ml based on C 0 level. Patients were divided into two C 0 (<100 and >100 ng/ml) and two C 2 (<800 and >800 ng/ml) subgroups. Discussion: Similar creatinine levels, drug dosage, and complications of C 0 and C 2 subgroups may be due to dependence of renal function to several factors other than cyclosporine dosage. Regarding coefficient of variation, C 2 was more accurate and reliable than C 0 level. As there was no significant difference in mean C 0 and C 2 levels, and renal function at beginning and the end of the study, there seems to be no need to check C 2 levels after renal transplantation. 

Purpose: preparation is necessary in order to effectively meet the critical needs of the post-operative pediatric kidney transplant patient upon their arrival to the ICU following transplantation. The increasing number of children requiring liver transplantation services has made it evident that it is important to have guidelines in place for their initial and often specialized post-operative care. Methods: the main goal is to provide the child with appropriate post-operative care and to recognize and quickly address complications. Therefore the ICU nurse will: · Monitor the patient continually and conduct full assessments a minimum of 1 time/hour (airway, breathing, ventilation, perfusion, neurological status, etc) . · Observe the incision for signs of bleeding, evisceration, and dehiscence. · Treat post-operative pain. · Update family with findings, etc. · See that appropriate post-operative studies (ultrasound, laboratory studies, etc) are completed. Outcomes: nurses in the ICU monitor the pediatric post-operative kidney transplant patients very closely as outlined. This allows for quick recognition of problems and immediate intervention. It is the practice of these nurses to be fully aware of the patient's status as well as any changes that might be problematic. Conclusions: nurses are prepared to care for pediatric kidney transplant patients and very carefully follow established guidelines for assessment. Following guidelines for assessing and caring for pediatric kidney transplant patients upon admission to the ICU has proven to be affective in allowing nurses to quickly recognize complications and notify the appropriate clinician. Background: Uremia is an independent cardiovascular risk factor. Transplantation increases life expectations of patients with CRF, however there is still an increased risk of accelerated arteriosclerosis. The pulse wave velocity (PWV) is a non-invasive marker of arterial distensibility, it increases along with arterial stiffness, as an early indicator of arteriosclerosis. Aim: to evaluate PWV values of transplanted (Tx) children. Patients, Methods: PWV was measured with a PulsePen in 21 Tx (age 14,3±3,0 years). Two control groups were formed using a database of 116 healthy children (6-23 years): one matched for age (A) and one adjusted for height and weight (H/W). Blood pressure, heart rate, serum Calcium (Ca), Phosphate (P) , and PTH were also determined before transplantation and at the time of the PWV measurement. Results: Tx patients were smaller by 15,3 cm (p<0,05) than A and younger by 2,9 years than H/W (p<0,01). PWV in Tx (5,5±0,7 m/s) did not differ significantly from A (5,1±0,9) , however it was elevated in comparison to H/W (4,6±0,6 p<0,01). Serum P, CaxP and PTH was increased before transplantation, all the values returned into the normal range except for creatinine (106±50 micromol/l) at the time of the study. There was no correlation between PWV and the actual values of Ca, P and PTH. Conclusion: PWV is higher in transplanted children as a sign of increased arterial stiffness. Controls matched for height and weight should be used in states of severe growth failure. Although a number of established risk factors potentially responsible for arterial dysfunction were present before transplantation, they were normal at the time of the study. The long lasting effect of uremia before transplantation could be in part responsible for the increased PWV in children after transplantation. Supported OTKA-T046155-FO48842-F042563 and ETT 435/2006.

D. Derakhshan 1 , H. Jalaeian 2 , A. Derakhshan Department of Pediatric Nephrology, Shiraz, Iran 2 Shiraz Organ Transplantation Center, Nemazee Hospital, Shiraz, Iran Backgrounds: Bartter syndrome is an inherited recessive autosomal tubulopathy characterized by hypochloremia, hypokalemia, metabolic alkalosis associated with potassium renal leakage, and normal blood pressure despite increased plasma renin activity. Patients with this syndrome may have proteinuria or hematuria, but most of them have normal GFRs. Here we report on a child with Bartter syndrome who developed ESRD (end stage renal disease) and underwent successful cadaveric kidney transplantation. Case presentation: a 7-year-old girl presented to the pediatrics nephrologist with failure to thrive, severe hypokalemia, hypochloremia, metablolic alkalosis, and normal blood pressure and the diagnosis of Bartter syndrome was considered for her. However, due to poor compliance, she did not receive any medications, did not give consent for kidney biopsy and did not attend her OPD follow-up visits for about 8 years, when she developed ESRD and went on chronic hemodialysis (3/weeks) . Her little sibling also was diagnosed to be suffering from Bartter syndrome at this time. After 10 months, she received a cadaveric renal allograft. Afterwards, her kidney function, serum electrolytes, and growth have improved dramatically. Discussion: In this case, we postulate that long-term hypokalemia due to Bartter syndrome led to chronic interstitial nephritis and renal dysfunction. Successful renal transplantation, even after the onset of ESRD, for Severe clinically Bartter Syndrome results in correction of metabolic abnormalities and excellent graft function. We propose that Bartter syndrome should be considered as a possible cause of ESRD and an indication for early renal transplantation, a procedure that results in a cure for the underlying disease and significant improvements in patient's quality of life.

H. Jalaeian 1 , A. Derakhshan 2 , D. Derakhshan 2 , M. Fallahzadeh 2 , Z. Bazargani 3 , M. Basiratnia 4 1 Shiraz Organ Transplantation Center, Nemazee Hospital, Shiraz, Nemazee Hospital, Shiraz, Iran 3 Fasa University of Medicine, Pediatrics, Fasa, Iran 4 Shiraz University of Medical Sciences, Pediatric Nephrology, Shiraz, Iran Background: Obesity is a major issue in the end stage renal disease population. While studies evaluating the effect of obesity on transplant outcomes in adults have yielded varying results, this issue is even still more controversial in children. Methods: In a cross-sectional design, 71 pediatric recipients, aged 4-19 at transplantation and with normal graft function for at least 7 months after transplantation, were evaluated. We grouped the data with regard to the body mass index (BMI) percentiles as group I (BMI >95th), group II (BMI <95th), group III (BMI >85th), group IV (BMI <85th). We compared the clinical and laboratory findings between groups I and II and between groups III and IV. Obesity was defined as BMI >95th and being overweight was defined as BMI >85th. Results: There were 71 children (45 males, 26 females) with mean age at time of transplantation of 12.6±3.5 years (range, [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] , and mean follow-up of 4.0±2.4 years. 12.7% of children were overweight and 5.6% were obese. No difference was found regarding age, height, duration of pretransplantation dialysis, or age at transplantation between groups I and II and between groups III and IV. (p>0.05). Further more, no difference was found in regard to serum creatinine, BUN, glomerular filtration rate, and 1-year graft survival rates among obese and/or overweight and other children. No correlation was found between BMI and GFR (p>0.05). Conclusion: Obese and overweight recipients can have excellent graft function and survival rates that are comparable to their non-obese counterparts. Denying patients access to renal transplantation on the basis of obesity per se does not appear to be justified.

D. Derakhshan 1 , H. Jalaeian 2 , A. Derakhshan 1 , B. Sabet 2 , M. Fallahzadeh Nemazee Hospital, Shiraz, Iran 2 Shiraz Organ Transplantation Center, Nemazee Hospital, Shiraz, Iran Introduction: TB is an important cause of morbidity and mortality in renal transplant recipients, especially in developing countries. This study was done to identify the incidence of tuberculin test positivity before transplantation as well as the influence on outcome of graft function and patient survival in children who receive renal allografts. Methods: All 196 children with ESRD who received a renal allograft between 1990 and 2006 were evaluated. As a routine pre-operative measure, a TB test was administered, using PPD. The PPDpositive recipients were compared with PPD-negative subjects, regarding age, gender, graft function, graft outcomes and patient survival rates. Patients were divided into <5 mm versus >5 mm induration. Results: The mean age of recipients was 14.03±3.20 years (range, 4-18) with a male/female ratio of 1.26:1. The majority of children were on chronic dialysis with mean duration on dialysis of 12.90±12.96 months. The tuberculin test was positive in 14.3% of children; all of them received isoniazide prophylaxis on diagnosis of latent tuberculosis. Overall, the 1-year, 2-year, and 3-year survival rates were 94.47±0.02%, 92.44±0.025%, and 88.86±0.03%. Three year survival rate was not different among PPD positive or PPD negative individuals. (90.00±0.09 vs. 93±0.03%; p>0.05) In addition, no difference was found for 1-year or 2-year graft survival rates (p>0.05). Also serial serum creatinine levels at 1-month, 6-month, 1-year, 3-year, and 5- year interval after transplantation was not statistically different (p>0.05). Conclusions: Detection of latent tuberculosis infection is an important step in the control of tuberculosis among asymptomatic pediatric kidney transplant. With proper management, latent TB does not affect transplantation outcome among children.

H. Xu, Q. Shen, Ss. Ruan, Yl. Bi, Yq. Lu, X. Wang Children's Hospital of Fudan University, Department of Nephrology, Shanghai, People's Republic of China Objectives of study: We have started the first pediatric renal transplantation project in children hospital in China from 2004. Survival of patients and grafts for the 5 patients are 100%. The clinical features were analysed and specific problems related to drugs and infections were reviewed. Methods: 5 children (9~16 years old) underwent RTx. The duration of follow-up was 4 months to 32 months (average of 19.8 months). Results: All the 5 patients were on automated peritoneal dialysis prior to RTx. The transplanted kidneys came from cadaveric donors (one were a 6-year-old brain-dead boy). 4 patients received IL-2 receptor antibodies as induction therapy and the other one with ALG due to high level of population reactive antibody. After the RTx, all the 5 patients were on triple immunosuppressive treatment (prednisolone, MMF, FK506 or CsA) . No patient developed postoperative complication and delayed graft function occured. During the follow-up, 1 case suffered from calcineurin inhibitor renal toxicity and changed to rapamycin treatment, 1 from acute respiratory distress syndrome due to infection and 2 from elevated liver enzymes owing to drugs. One had acute rejection at 2 months after the operation. A severe anemia appeared on him after the rejection recovered. The cause of the anemia was found by the positive of serum anti-parvovirus B19 IgM and completely recovered from the IVIG treatment. At latest follow-up, the mean serum creatinine level of the 5 patients was 84.4±36.5 umol/L and eGFR was 118.0±38.8 ml/min/1.73 m 2 . Some patients received a support from "Shanghai Child Renal Failure Trust Fund". Conclusions: The improvement of surgical technique, adequate dialysis prior to RTx, rational use of medicine, financial support and regular follow-up are all important for improving the outcome.

H. Bunker-Wiersma 1,3 , J-C. Davin The area under the curve (AUC) of cyclosporine is strongly related to the efficacy and toxicity of the drug and its variability is mainly determined by the absorption phase. Close therapeutic drug monitoring (TDM) is warranted to optimise therapy, using more appropriate methods to estimate the AUC, than trough concentration measurement. From July 2004 we started AUC guided monitoring of cyclosporine therapy based on two concentration measurements, C0 and C2. The results of this method are reported. Methods: All paediatric renal transplant recipients treated with cyclosporine were included in the analysis. Bayesian, model based estimation of AUC values was performed at each out-patient visit or during hospital admission. Calculated pharmacokinetic parameters, treatment efficacy data and side effects were collected over the 18 month period after introduction. Target AUC values were derived from previous studies in adult patients: 5400 ng/h/ml in the first three months after transplantation and 3250 ng/h/ml after three months. Results: 15 early or stable post renal transplant patients were evaluated, divided in two groups (group I: <3 months after transplantation; group II: >3 months after transplantation). In patients with trough concentrations below the therapeutic range, more than 50% AUC's were in the therapeutic range in both groups. Conclusion: AUC guided monitoring of cyclosporine after kidney transplantation in children using C0 and C2 is practically feasible and presents the major advantage that C2 has not to be determined precisely 2 hours after CsA administration. It is more closely related to the total drug exposure as compared with trough concentration monitoring and isolated C2. This method may facilitate the use of lower doses of cyclosporine and by this way limitside-effects. Objectives: There is no satisfying data about reproductive functions after kidney transplantation in adolescence who have end stage renal disease (ESRD) during childhood. We analysed the reproductive functions of kidney transplanted male adolescences. Patients and Methods: Nine patients who followed between 1995-2006 were enrolled in the study. Except one preemptively transplanted patient, all were on hemodialysis/peritoneal dialysis before transplantation. Mean dialysis duration was 21 (9-54) months. Their ages ranged between 10-17 years (mean 13.8) at transplantation. At the urologic examination, their mean age was 19 years. All patients had normal renal functions. Results: All patients had normal testicular volume, libido and erectil functions. Except one all patients had normal serum levels of LH, FSH, total and free testosterone. Seven of the 9 patients semens were available for analysis. 3/7 patients had normal sperm parameters. Transplantation had been performed before adolescence period in these 3 patients. One of these patients had been treated with intensive cyclophosphamide before. Oligospermia was detected in 2, defective morphology in 3, low sperm motility in 6/7 patients. Conclusion: Although adult transplanted patients mostly have normal semen profiles; male children with end stage renal failure would not have normal spermatogenesis at the adolescence period; even after successful renal transplantation. In our study only 3 patients had normal semen profile, even hormon levels were normal. Renal transplantation age seemed to be more crucial than the duration of ESRD, of primary diagnosis or previous cyclophosphamide usage.

R. Vilalta, J. Nieto, E. Lara, A. Madrid, S. Chocron Hospital Materno-Infantil Vall de Hebron, Department of Pediatric Nephrology, Barcelona, Spain Background: Inhibition of IL-2 receptors by basiliximab is irreversible and extended in time (mean 30 days). Basiliximab (anti CD25 receptor) is used usually in the induction regime in our first cadaveric-donor kidney transplants. Its re-use when chronic allograft nephropathy (CAN) develops could be useful. However some concern could exist related to possible adverse reactions (anaphylactic shock) linked to re-exposure to this drug because is an heterologous protein. Less adverse reactions as lymphokine release syndrome has been described with the use of other monoclonal antibodies as the anti-CD20 receptor rituximab. Objective: To describe our experience in the treatment with basiliximab of seven children with Banf II CAN. Patients: Seven children (2-16 years old (means 8.2 y.), 5 boys, 2 girls) showed biopsy-proved Banf II CAN. Its period post-transplant ranged from 2 to 5 years (mean 4.1 y.) and their creatininine level from 2 to 4 mg/100ml (mean 3.2). All of them had been received at the transplant time basiliximab, tacrolimus or cyclosporine, mycophenolate and tapered steroids to reach 0.2 mg/kg/day in the third month post-transplant. When CAN developed, sirolimus was used in two patients, but was withdrawn due to increase of proteinuria. Results: One dose of basiliximab (20 mg/1.73 m 2 ) was administered after 3 steriod pulses (10 mg/kg/day) in all patients. Their basal immunosuppression was not changed. Plasma creatinine diminished by 30% in four patients in the second week post-treatment and this improvement was sustained in two patients after one year follow-up. Proteinuria did not change in any patient. In the course of this treatment no adverse reactions were observed. Conclusion: 1) Use of basiliximab in CAN is safe and possibly useful.

2) Exposure to different monoclonal antibodies in paediatric kidney transplantation could be usual in the future; in the induction time, in the treatment of humoral rejection if exists (rituximab) and in the treatment of CAN.

3) It is necessary to establish that exposure and re-exposure to different antibodies is safe and without major adverse effects as our limited experience supports.

R. Vilalta, E. Lara, A. Madrid, S. Chocron, J. Nieto Hospital Materno-Infantil Vall de Hebron, Department of Pediatric Nephrology, Barcelona, Spain Background: There are limited knowledge of kinetics and pharmacodynamic effect of sirolimus in paediatric renal transplantatation. Provided that sirolimus is effective and safe in combination with tacrolimus and mycophenolate (MMF), the initial dose needed, the evolution of blood levels and the steady state should be studied in order to optimise its clinical use. Objective: To establish a possible correlation between dose/level ratio of rapamune and other parameters as age, gender or puberal state. Patients and methods: Between 2000 and 2006, 19 paediatric patients (11 girls, 8 boys) received a cadaveric kidney transplant. Age ranged from 4 to 16 years (mean 8 y.), and all of them received MMF and steroids. Sirolimus were used from 0.02 to 0.1 mg/kg/day, to obtain levels between 6 to 12 ng/ml. Results: Dose/level ratio obtained allowed us to describe three types of patients: An infant-type I dose-level patient (age 4-8 y), a prepuberal type II (age 8-12y) and an adult-type III dose-level patient (age 12-16y). Type I needed sirolimus between 0.08 and 0.1 mg/kg/day (SD±0.01), type II between 0.04 and 0.8 mg/kg/day (SD±0.015) and type III between 0.02 and 0.04 mg/kg/day (SD±0.018) to obtain all of them a constant blood levels between 6 and 12 ng/ml. The same positive correlation was obtained regarding the puberal status. No correlation were observed regarding the gender. Introduction: Developing of diabetes mellitus after renal transplantation is one of the determining factor in the survival of the patient and the graft. In present study we assessed the carbohydrate metabolism status of NTx. Methods: We analyzed 45 patients' data about recently developed carbohydrate metabolism failure after NTx. Children underwent NTx between 1990-2005 were investigated. Thirty-nine children (16 girls/23 boys) underwent OGTT, who had no PTDM. We analyzed the incidence of PTDM/IGT, the combination of immunsuppressive therapy, the number of transplants, the proportion of cadaver/living donor, HCV, blood pressure, lipid metabolism, BMI, graft function parameters and the time since NTx. Results: PTDM developed in 6 children (13%). Four of 6 patients required insulin therapy. We diagnosed IGT in 7 of 39 with OGTT investigated patients (16%). All PTDM/IGT patient got tacrolimus and continous steroid therapy. The dose of steroid was 6.5 mg/day in the PTDM/IGT group vs. 5.2 mg/day no PTDM/IGT (p<0.05). During OGTT the trough level of tacrolimus was higher in the PTDM/IGT group 14.3 ng/ml vs. 10.1 ng/ml (p<0.05). In the other parameters we did not find any significant differences between PTD/IGT and no PTDM/IGT patients. Discussion: The most important reasons in the development of PTDM and IGT after transplant are steroid therapy and higher tacrolimus trough level. In transplant children we recommend the regular fasting glucose and OGTT examimation, the reduction of steroid and tacrolimus in case of stable graft function. OTKA F-042563, OTKA-T046155, ETT 435/2006 , ETT 184/2003 

The Introduction: Measurement of plasma BNP is a novel noninvasive approach in the assessment of cardiovascular status. In our study we investigated the role of BNP in the monitoring of cardiovascular status of children with CRF or renal transplant (NTx). Methods: We examined 32 children with CRF (n=17, 11 boys/6 girls, age: 12,1 year (3,5-20)) or NTx (n=15, 9 boys/6 girls, age: 16, 25) ). Patients underwent echocardiographic investigations (IVS, LVEDd, LVESd, PW and FS) and their BNP levels were measured (age matched normal values were used). Other cardiovascular risk factors, such as Hgb, Htk, Ca, P, creatinine and blood pressure were also evaluated. A correlation between BNP and echocardiographic results was calculated. Results: The values of LVESd, FS and BNP levels of renal transplant patients were significantly better than those of CRF patients (p<0,05). The other parameters did not show significant differences. BNP levels were significantly higher in all age groups of CRF patients as compared to the normal levels. In younger NTx patients this value was within normal limits. In older NTx patients, and in those that had their transplants a long time ago we measured higher BNP levels, which correlated significantly with graft function as well (p<0,05). BNP showed a significant positive correlation with LVESd and a significant negative correlation with FS only in CRF patients. The elevated BNP levels showed the worsening of cardiac function even when the echocardiographic parameters were still normal. The Hgb, Htk, Ca, P and creatinine values were significantly better in NTx patients and showed no correlation with BNP. Summary: BNP is an early, easily usable marker in diagnosing and following decreased cardiac function of both CRF patients and after NTx. OTKA F-042563, OTKA-T046155, ETT 435/2006 , ETT 184/2003 

C. Garcia 1 , V. Bittencourt 1 , S. Vitola 3 , E. Didone 3 , E. Guerra 3 , F. Pires 3 , A. Tumelero 1 , D. Malheiros 1 , V. Garcia Department of Pediatric Nephrology, Porto Alegre, Brazil 2 Complexo Hospitalar Santa Casa, Department of Nephrology and Kidney Transplantation, Porto Alegre, Brazil 3 Complexo Hospitalar Santa Casa, Department of Surgery, Porto Alegre, Brazil The objective is relate the results of 348 consecutive kidney transplants carried out in children in a single center. Patients and Methods: analysis of kidney transplants performed in patients less than 18 years old, carried out from May 1977 to December 2006. Results: 348 kidney transplants were performed. 48% of the patients were female, 86% were Caucasian and 14% were African-Brazilian. The mean age at the transplant was 11.3±4.5 years. The most frequent etiology of renal failure was vesico-ureteral reflux/obstructive uropathy (35%), followed by glomerulopathy (26%). The donor was deceased in 34% and living related in 66% (parents 82%). The initial immunosuppression was CyA+AZA+PRED in 38.9%, CyA+MMF+PRED in 6,9%, TAC+AZA+PRED in 8.6%, TAC+MF+PRED in 23.9%, TAC + MF without PRED in 8.9%. Sirolimus was employed initially in 4 cases. Induction with OKT3/ATG occurred in 5 patients and 157 received anti-IL2 receptor antibody. The 110 graft losses during 29 years of follow-up were secondary to chronic allograft nephropathy in 58 (51%), vascular thrombosis in 6 (5.2%), acute rejection in 13 (11.2%), recurrence of original disease in 14 (12.1%). There were 27 transplants in 21 patients with focal segmental glomerulosclerosis, 12 (57.1) had a recurrence after transplant. Eight were treated with plasmapheresis and 75% obtained a total remission. The survival of graft in the first, fifth and tenth year was: 90%, 72% and 59% respectively. The graft survival in the 5th year according the immunosuppression was 41% using azathioprin and prednisone, 72% with CyA/Aza or MMF and 78% with Tac/Aza or MMF. The patient survival in the first, fifth and tenth year was: 95%, 93% and 85% respectively, infection was the main cause of death.

J. Feber 1 , P. Geier 1 , B. Chaudry 1 , H. Wong 1 , G. Filler 2 1 Children's Hospital of Eastern Ontario, Division of Pediatric Nephrology, Ottawa, Canada 2 London Health Science Center, Departments of Pediatrics, London, Ontario, Canada Successful pediatric renal transplantation (Tx) should fully correct the metabolic abnormalities of end-stage renal failure. However, CKD may persist because of only half of the normal nephron endowment and other factors (ischemia, nephrotoxocity etc). Height, BMI and blood pressure (BP) Z-scores, cystatin C-GFR, hemoglobin (Hb), serum PTH, HCO 3 , cholesterol, mycophenolic acid (MPA) and sirolimus (SIR) levels were analyzed retrospectively in 21 Tx recipients (10 males, age 8.5±5.8 years) at 4 months post Tx (T1) and at 3.26±2.21 years (median 2.4) post Tx (T2). Data are expressed as mean±SD. Height Z-scores remained significantly lower than controls (T1: -0.90±1.17; T2: -0.75±1.23, NS), growth failure occurred in 19% of pts at T1 and 26% of pts at T2. BP Z-score did not change from T1 to T2, but hypertension was diagnosed in 66% pts at T1 and 79% pts at T2. GFR (ml/min/1.73 m 2 ) was 71.9±18.6 at T1 and 70.9±23.7 at T2 (NS), mean decline of GFR was 3.9±1.1%/year. Hb Z-score remained below normal at -1.55±2.04 at T1 and -1.10±1.27 at T2 (NS) and anemia was diagnosed in 62% and 63% of pts at T1 and T2 respectively, despite trough levels of both MPA (2.77±1.43 mg/ml, 11 pts) and SIR (7.73±2.55 mg/ml, 10 pts) that would be considered adequate. Hypercholesterolemia was detected in 23.8% pts at T1 and 42% pts at T2, whereas only 9.5% of pts at T1 and 16.8% of pts at T2 were labeled as obese. Bone disease was diagnosed in 28.5% pts at T1 and 15.8% pts at T2. We observed suboptimal growth, hypertension, hypercholesterolemia, bone disease and persistent anemia in a significant proportion of Tx children despite iron supplementation, adequate MPA and SIR levels and good kidney function. These CKD complications require careful monitoring and intervention.

A. Al Midani 1 , G. Koffman 2 , J. John 2 , S. Stephen 2 , S. Suzanne 2 , R. Lord 2 1 Royal Free Hospital, Transplantation, London, United Kingdom 2 Great Ormond Street Hospital for Children NHS Trust, Transplantation, London, United Kingdom Objectives: To document factors predisposing towards surgical complications over 7 years in a single pediatric renal transplant centre. Methods: We retrospectively analysed 179 consecutive renal transplants between Jan 2000 and Dec 2006. Patients were divided into group 1, without complications, and group 2, with complications. We compared variables previously identified as risks for surgical complications between the two groups: live/deceased donor, donor and recipient age, gender and weight, side of organ donation, cold ischaemia time, single/multiple vessels, intraperitoneal/extraperitoneal approach, anastomosis to aorta/iliac vessels, thrombosis prophylaxis (changed from heparin to aspirin in Oct 2000). Results: 141/179 (81%) were complication free; 19% patients developed one or more surgical complication: wound infection 2/179 (1.1%), wound dehiscence 3 (1.7%), prolonged ileus 1 (0.5%), lymphocoele 7 (3.9%). 7 patients were re-explored: 5 (2.8%) for bleeding, 2 (1.1%) for graft repositioning. We observed 2 (1.1%) cases of renal artery stenosis. Overall, 5 (2.8%) graft loss occurred secondary to thrombosis, 13% (3/23) prior to changing our prophylaxis from heparin to aspirin (1.2% on aspirin). Urological complications occurred in 7 (3.9%): 3 ureteric leaks and 4 ureteric stenoses. The variables between group 1 and group 2 were as follows: under 20 kg: 19% v 35%, less than 5 yrs old: 12% v 30%, intraperitoneal approach: 13% v 37%, anastomosis onto the aorta: 18% v 43%, no aspirin prophylaxis: 9% v 24%, other variables were the same in both groups. Conclusions: 19% of patients developed surgical complications. A higher rate of surgical complications was seen in recipients under 5, using the intraperitoneal approach onto the aorta. The introduction of aspirin prophylaxis reduced graft loss due to thrombosis from 13% to 1.2%. Other variables did not affect the complication rate.

M. Medeiros 1 , V. Sharma 2 , R. Ding 2 , S. Valverde 1 , AM. Hernández 1 , P. García 1 , Y. Fuentes 1 , M. Suthanthiran 2 1 Hospital Infantil de Mexico Federico Gomez, Departamento de Nefrologia, Mexico, Mexico 2 Weill Cornell Medical College, Immunogenetics and Transplantation Center, New York, NY, United States The forkhead transcription factor FOXP3 is highly expressed in CD4+CD25+ regulatory cells (Tregs). The FOXP3+CD25+CD4+ cells play a central role in immune tolerance and TGF-β 1 is reported to induce FOXP3 expression in vitro. Whether there is an in-vivo association between FOXP3 and TGF-β 1 is not known. We investigated the hypothesis that there is a positive association between FOXP3 and TGF-β 1 in children with stable renal graft function. Parental written informed consent was obtained before enrollment in all cases. 24 children with stable renal allograft function for a minimum of 12 months were studied. A complete clinical examination was performed; peripheral mononuclear cells were collected for measurement of transcripts for FOXP3, TGF-β 1 , TGF-β 2 , and 18s rRNA (house keeping gene) using by real time quantitative PCR assay. Correlation between transcript levels was performed using Pearson r. Results: 24 pediatric recipients of renal allografts were studied. TGF-β 1 and FOXP3 were highly expressed in peripheral blood mononuclear cells, and there was a highly significant and positive correlation between levels of mRNA for FOXP3 and TGF-β 1 (r=0.811, p<0.0001)), whereas no significant correlation was found between TGF-β 1 vs. TGF-β 2 (and TGF-β 2 vs. FOXP3). Conclusion: FOXP3 expression in vivo is strongly correlated with TGF-β 1 expression in peripheral mononuclear cells of stable renal transplant recipients. Introduction: Studies suggest that pre-emptive lamivudine therapy improves survival in HBV renal transplants. However, long-term outcome is not well established. Method: Four Chinese adolescents with chronic HBV infection were transplanted. They were put on cyclosporin A, mycophenolate mofetil and prednisolone. Prophylactic lamivudine was given just before transplantation and was continued afterwards. HBV status and liver enzymes were monitored serially.

Results: Four patients were transplanted at the age of 15.5±3.0 (13.9-19.9) yrs old. They were followed up for 74.7±10 (61-85) months and no mortality was reported. Alanine transaminase (ALT) was only transiently elevated in the first 2 months post-transplant in all cases and became normal afterwards. There was no hepatitis flare and liver function was normal at the last follow-up. HBeAg and HBV DNA were positive in 1 patient before transplantation and remained positive at the latest follow-up. Mutation in the YMDD motif of the HBV genome was detected in the same patient and undeterminable in the other three due to low virus load. This patient remained clinically stable with normal liver function except there was a rise of viral load from baseline. All grafts were functioning and there was one late acute cellular rejection which responded to treatment and there was no hepatitis flare. Latest mean serum creatinine was 141±63 (56-208) umol/L. Conclusion: YMDD mutation and resistance to lamivudine treatment may happen but appear to have little clinical significance. Our long-term results showed that renal transplant seems feasible and safe in this population up to 7 yrs follow-up. There are no studies in Mexican children (MX) . The aim of the study was to determine tacrolimus pharmacokinetics (PK) in Mexican renal transplant children and compare it wih reported PK in AA and CA.

Methods: A seven point pharmacokinetic profile (0, 0.5, 1, 2, 4, 8 and 12h) was performed in ten children receiving tacrolimus as part of the immunosuppressive therapy, mean age was 13.9±2.19 years, mean post transplant time 9.8±35 months. C0 and Cmax were obtained directly from experimental points, the AUC and t1/2 was obtained with a non-compartmental model using WinNonLin version 3.0.

Results: In Cyclosporine (CsA) is widely used for immunsuppression in transplant recipients and for treatment of SRNS. However, patients can develop CsA associated cutaneous side effects, e. g. hypertrichosis, skin cancer, and viral warts due to human papillomavirus infection. Here we report on a 23-yearold boy suffering from a microdeletion syndrome (18 q-) and SRNS (histology: minimal change nephropathy) starting at the age of 20 years. Since the initial combination therapy with corticosteroids and cyclophosphamide was associated with severe side effects (sepsis, leukopenia) and did not lead to sustained remission CsA therapy was initiated. CsA-treatment resulted in rapid clinical remission. However, after 12 months the patient developed viral warts (hands, trunk and head), although CsA trough levels were kept below 100 μg/l. Therefore, immunosuppression was switched to MMF (2x500 mg/day) resulting in sustained remission of SRNS and rapid disappearance of viral warts within 4 months.

Conclusion: Conversion to MMF may be a usefull treatment strategy in SRNS showing CsA associated side effects like viral warts. 2003-2006. 5 were live related (LRD) and the remaining cadaveric (CAD). 6 were pre-emptive(PET). All received Basiliximab induction 2 hrs prior to surgery. In addition, induction immunosuppression consisted of Tacrolimus and methylprednisolone. In all but 2 patients, Basiliximab was re-administered at day 4. 2 patients, aged 11 and 6 yrs (one CAD and other LRD respectively) developed acute noncardiogenic pulmonary oedema 6-48 hrs after transplantation. Both children had renal dysplasia as primary cause of renal failure. Both required delayed ventilation and were ventilated for 4 to 6 days respectively. There was a rapid rise in C Reactive Protein in both patients. Both grafts had primary function, but the CAD transplant subsequently developed acute tubular necrosis, and was eventually lost within 3 weeks due to thrombotic micro angiopathy and severe acute antibody mediated rejection despite immunosuppression with sirolimus, mycophenylate, steroids and plasma exchange therapy.

Conclusion: We report a rare but serious side effect of Basiliximab. To our knowledge, this is the first report of basiliximab induced non-cardiogenic oedema so early post transplantation and in such young children. Early recognition and aggressive appropriate supportive therapy is vital for patient and where possible, graft survival.

3 (17); CMV seroconversion (4); seizures (4); hypertension (9), UTI (6), adverse reaction to basiliximab (2), delayed graft function (4), acute rejections (2), chronic allograft nephropathy (1). 17 patients had well matched kidneys (3 or less mismatches), 11 were poorly matched. 2 grafts were lost from latter group, both were CAD, 1 had acute tubulointerstitial nephritis and tacrolimus toxicity and the other thrombotic microangiopathy and eventually acute antibody mediated rejection. Chronic allograft nephropathy (CAN) is a complex phenomenon caused by underlying kidney disease and superimposed by environmental and genetic factors. We investigated the association of polymorphism in the genee NOS with the CAN. Nitricoxide is synthesized from L-arginine in vascular endothelial cells by nitric oxide synthase. Endothelial nitric oxide plays an important role in endothelial dysfunction and involved in the inflammation. The gene encoding eNOS maps to chromosome 7q35 7q36.7. A missense variant of the eNOS gene in exon 7 shows a transversion of G to T at nucleotide position 894 (G894T) that results in a replacement of Glu by Asp at amino acid residue 298 (Glu298Asp). The aim was to investigate the association between CAN and G894T polymorphism of the endothelial nitric oxide synthase gene. The G894T mutation at exon 7 of the endothelial nitric oxide synthase gene, eNOS gene polymorphism, was analyzed in 61 Turkish children with renal transplantation. The G894T polymorphism of the endothelial nitric oxide synthase gene was determined by polymerase chain reaction and restriction fragment length polymorphism. were grouped according to stages of chronic kidney disease (CKD) as estimated by the calculated glomerular filtration rate (GFR, Schwartz formula). Measurements of structural and functional surrogates for cardiovascular disease (CVD) included intima-media thickness (IMT) of the common carotid artery (CCA), pulse wave velocity (PWV) and augmentation index (AIx). AIx and PWV reflect the degree of arterial stiffness and were calculated from pulse wave recordings at the arteria carotis and arteria femoralis (SphygmoCor device). Results: Patients and healthy control subjects had a mean age of 14 years. IMT was not significantly different in patients and controls. Significant differences were found in the Aix, which was increased by 50%: the mean AIx was in healthy subjects was -28,2% and in transplanted subjects -14,4%. PWV was increased by 15% (4,74 m/s vs. 5,43 m/s). Both AiX and PWV increased in parallel with the degree of renal impairment (stages of CKD). Table 1 .

Discussion: Weight gain post transplant is multifactorial, like cultural, psychological and associated to steroids. Weight gain was observed in general, patients with overweight or in risk of overweight didn't loose weight postransplant even they were aware of the consequences. Introduction: Tacrolimus is metabolized by cytochrome P450 3A and has a narrow therapeutic range. We report a kinetic interaction between tacrolimus and amlodipine, a potent cytochrome P450 inhibitor, resulting in anuric acute renal failure. Case report: A 14-year-old male renal transplant recipient received amlodipine, a calcium channel blocker as antihypertensive treatment while he was on tacrolimus (0.1 mg/kg per day). He presented first with diarrhea and developed subsequently, dizziness and fatigue, related to acute anuric renal failure, requiring hemodialysis for 20 days. Tacrolimus trough levels were in the desired therapeutic range (3-6 ng/mL) until recently. Three days after introduction of amlodipine, tacrolimus trough levels increased to a toxic level of 38.8 ng/mL. After discontinuation of amlodipine, tacrolimus levels returned to the normal range in seven days and renal function recovered progressively. No polymorphisms in the expression of CYP3A and P-glycoprotein were detected. Discussion: Tacrolimus is known to be a substrate of P-glycoprotein, responsible for drug secretion into the intestinal lumen and metabolized by enterocytic CYP3A. Amlodipine is a competitive inhibitor of CYP3A. As no abnormalities of CYP3A and P-glycoprotein were found, we suspect that drug interaction due to competitive inhibition of tacrolimus metabolism by amlodipine was responsible for these toxic effects. Concomitant diarrhea might have played an additional role for increased tacrolimus serum levels, presumably in relation to diarrhea associated dysfunction of enterocytic CYP3A and P-glycoprotein. Conclusions: Amlodipine and diarrhea increase tacrolimus blood concentration by inhibiting its metabolism. Amlodipine should not be used in patients on tacrolimus. Careful monitoring of tacrolimus blood levels is recommended in case of concomitant diarrhea.

Urinary tract infection (UTI) remains a significant cause of infectious complications in renal transplant recipients. The aim of the study was to determine the frequency of UTI following renal transplantation in our center. The records of 34 patients (F/M: 14/20) who underwent renal transplantation were evaluated retrospectively. Among them 12 patients (F/M: 9/3) were found to have at least one episode of UTI during follow-up. The records were examined for the age, sex, primary disease, and duration of chronic renal failure, donors, posttransplant follow-up and recurrence of UTI. Biochemical analysis of blood for renal functions, complete blood count, Creactive protein and sonographic examination of patients were also recorded and results were compared with renal transplanted patient who did not develop any episode of UTI (group 2). The mean age of the group 1 was 14.6±4.7 years, while it was 14.5±3 years in the group 2. Mean duration of post-transplant follow-up was 2.8±1.7 years for group 1 and 2.4±1.7 for group 2. Four patients (33.3%) in group 1 and 7 patients (33.3%) in group 2 had vesicoureteral reflux (p>0.05). Five patients had single UTI while 7 patients had more than one UTI. Though we did not find any difference between girls and boys in terms of presence of vesicoureteral reflux, frequency of UTI in girls was found to be significantly higher than in boys (p=0.003). Ultrasonographic examination of patients during UTI in group 1 revealed pyelonephritis in 3 and hydronephrosis in 2 patients. The most frequent microorganism causing UTI was E. coli. Age, donor source and etiology of chronic renal failure did not influence the incidence of urinary tract infection. Our data suggests that urinary tract infection remains a frequent but mostly benign complication in the pediatric transplant population, especially in female gender. The growing population of transplanted patients requires the consideration of the potential side effects of the different treatment regimens. Experience of the last decade with calcineurin and nucleoside reverse transcriptase inhibitors revealed important renal side effects. We describe a 15 years old girl who was known to have liver failure related to Wilson's disease (WD). She had orthotopic liver transplantation from her mother 3 years ago and treatment with tacrolimus and MMF was initiated. Although she was known to have proximal renal tubular acidosis secondary to WD, renal tubular functions were found to be normal within the three months of transplantation. Two years after the transplantation lamivudine was initiated because of de novo Hepatitis B infection in transplanted liver. A couple of months later she developed renal Fanconi syndrome with metabolic acidosis, hypophosphatemia, glycosuria and aminoaciduria. She needed high doses of sodium bicarbonate and phosphate supplementation. Tacrolimus was suspected to be the cause of late post transplant renal acidosis and was replaced by sirolimus. However, 3 months later, at the 6 th month of lamivudine treatment, she was hospitalized because of metabolic acidosis, mild hyperglycemia and inability to walk. Electromyographic examination revealed myopathic changes while liver biopsy was normal with a normal tissue copper level. Renal biopsy showed findings of karyomegalic nephropathy which could be the result of the action of antimitotic agents. We suspect that our patient's tubular dysfunction, myopathy and hyperglycemia may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine. However, randomized and prospective studies with large groups of patients are needed for definite results about mithocondrial side effects of these drugs. Recombinant factor VIIa (rFVIIa, NovoSeven) is a new hemostatic agent that was initially indicated in hemophiliac patients. Recently it has been used successfully for the treatment of bleeding in patients with thrombocytopenia, and acquired and congenital platelet dysfunction. Epstein syndrome, also known as Alport-like syndrome, is a rare autosomal dominant disease characterized by proteinuria, chronic renal failure, hearing loss, and thrombocytopenia with giant platelets. Our group previously reported functional alterations of giant platelets of boy with Epstein syndrome, who rapidly progressed to end stage renal disease during adolescence. The first nonheartbeating kidney transplantation at age 17 was failed because of the severe postoperativebleeding irresponsible for traditional therapy (packed red cells, platelets, and fresh frozen plasma), result in immediate graft failure and the need for transplant nephrectomy. The second kidney transplantation was 4 years later, after a single intravenous bolus injection 70 μg/kg body weight rFVIIa, which was repeated one and 12 hours after the surgery. rFVIIa successfully controlled the bleeding in the peri-and postoperative phase and no side effect and thrombotic complication occurred and his graft function is still stable after 4 years. Recombinant factor VIIa may have a potential role in the treatment of phenotypic bleeding associated with chronic kidney disease. Cyclosporin A (CsA) and mycophenolic acid (MPA) have a wide interindividual variability in their pharmacokinetics (PK). Among others, intestinal P-glycoprotein (P-gp) expression and CYP3A4 activity have been held to be responsible for that variability. In adult kidney transplant (Rtx) patients, an influence of these gene polymorphisms has not been shown; however, there are no data in pediatric patients. We reasoned that such an influence might be masked in adults by confounding environmental factors accumulating over the decades of life. We therefore investigated a possible influence of gene polymorphisms of P-gp and CYP3A4 on defined dose-adjusted PK-parameters in 70 children with Rtx (age 11.6; range, 3.2-17.4 yrs). PK parameters (AUC, C2) were assessed 1, 3, 12, and 24 weeks after Rtx. Real-time, rapid-cycle PCR methods were used for genotyping. The allele frequencies for the MDR1 C3435T allele (expression and in vivo activity of P-gp) of 62% and for the CYP3A4-V allele of 3% were comparable to those reported for Caucasian populations. Dose-adjusted PK parameters of CsA and MPA were not significantly different in patients with and without the CYP3A4-V allele or patients with different MDR1 C3435T genotypes. Along with that finding, neither of the polymorphisms investigated into was associated with renal function or the incidence of acute rejection episodes. We studied how the IL-2R β-chain becomes enriched in lipid rafts of activated human T cells, isolated by Ficoll gradient and sheep red cell rosetting, and how its tyrosine phosphorylation, which requires its heterodimerization with the common cytokine R β-chain (βc), occurs there. Imunoblots (IBs) of sucrose gradient fractions of cell lysates obtained during a 72-hour activation with phytohemeagglutinine (PHA) showed the gradual, largely selective, translocation of the β-chain into rafts. As dimerization or lipid modification can be mechanisms underlying raft enrichment, we assessed lysates of PHA-activated cells in IBs under non-reducing versus reducing and crosslinking conditions but did not see evidence of β-chain dimerization. However, exposure to cycloheximide to interfere with post-translational acylation, or to the palmitic acid analogue 2-bromohexadecanoic acid substantially diminished raft enrichment of the IL-2R β-chain. We next performed IBs of IL-2R β-chainand βc-immunoprecipitates from raft and non-raft fractions of activated T cells before and after IL-2 treatment. We found that IL-2 exposure triggers the translocation of small amounts of βc, accompanied by IL-2R β-chains, into rafts, resulting in its heterodimerization with the IL-2R β-chain and their tyrosine phosphorylation. All of these processes were attenuated in the presence of the IL-2R β-chain-blocking antibody daclizumab. We conclude that the raft enrichment of the IL-2R β-chain requires palmitoylation and provides the focal point for the formation of the highaffinity IL-2R via IL-2R β-chain-mediated "chaperoning" of few βcs into these domains, establishing novel raft-dependent mechanisms underlying cytokine R specificity and selectivity in human T cells. IgA nephropathy (IgAN) is an immunecomplex disease resulting from a defect in mucosal IgA response. Food antigens have been implicated in the pathogenesis. Gut permeability to antigenic substances is immature at birth and its maturation is delayed by early administration of antigenic foods while breast feeding accelerates this process. We aimed to evaluate if exposure to antigenic foods in early life is associated with a predisposition for IgAN in childhood. Three groups including children with IgAN (Group 1, n=33), primary non-IgA glomerulopathies (Group 2. n=25) and healthy controls (Group 3, n=40) were formed. Their parents filled a questionnaire regarding the age at diagnosis, gestation time, birth weight, feeding by breast milk, formula, cow's milk and complementary foods. All groups were similar for age, sex, gestation period, birth weight and the rate and duration of breast feeding. In addition, the rate of formula feeding was also similar in all groups. However, cow's milk consumption rate was higher in Group 1 and 2 than in Group3. Introduction of formula was earlier in Groups 1 and 2 than in Group 3. In addition, the children in Group 1 were younger than the other groups at the onset of feeding by cow's milk and weaning. ROC curves predicted 3.5, 3.75 and 5.5 months as the best cut-off age values for formula feeding, cow's milk feeding and weaning for predicting the presence of IgAN, respectively. ORs for IgAN with respect to these cutoff levels were 28 (95% CI: 4-189), 5.7 (95% CI: 1.9-17.2) and 10.5 (95% CI: 3.9-28.0), respectively. The results of this preliminary study indicate that early introduction of antigenic foods might increase the risk of future primary IgAN. Results: They were 8 males and 2 females, with a male: female ratio of 4: 1. Their ages ranged from 5 months to 15 years (mean 6.8 years), with a peak age of 5-9 years. The common presenting complaints were generalised oedema (60%); oliguria (50%) and hypertension (50% We report nine patients (three males) with mesangiocapillary glomerulonephritis (MCGN) from a single paediatric nephrology centre. The average age at presentation was 12.0 years (range 9.2 to 13.4). All had nephrotic syndrome. Seven had MCGN type 1 and two had MCGN type II. Six of seven tested had positive C3 nephritic factor. Three patients responded well to steroids and ACE inhibitors and received no further therapy. Five had a good response initially but relapsed when steroids were tapered and one patient had a poor response to steroids. These six patients received calcineurin inhibitor (CI) therapy. Four responded well with resolution of proteinuria. One patient relapsed when tacrolimus was withdrawn after 23 months of therapy but proteinuria resolved after re-introduction of therapy. Two patients had a poor response to CI therapy. One remains stable but with heavy proteinuria. The second patient (with MCGN type II) initially had a complete remission of proteinuria on steroids but relapsed 30 months after presentation while on prednisolone 5 mg on alternate days. Repeat biopsy showed 65% crescents. Treatment with pulsed intravenous steroids, cyclosporin and mycophenolate mofetil was ineffective and she progressed rapidly to end stage renal failure. We conclude that CI treatment might be useful in mesangiocapillary glomerulonephritis. Prospective, randomised controled trials are required to determine their place in the management of this disease. IgA nephropathy (IgAN) is caused by a primary defect in mucosal IgA response leading to increased antigenic stimuli reaching to bone marrow. Enteric flora is important for mucosal and systemic immunity, and probiotics regulate specific and innate immunity by maintaining microbial balance in the gut. Saccharomyces boulardii (S.boulardii), a probiotic, increases intestinal sIgA production, protects enteric infections and also prevents atopic and immunoinflammatory diseases. We aimed to evaluate the effect of S.boulardii on experimental IgAN, induced by oral polio virus vaccine (OPV) administration to the mice. Four groups of male BALB/c mice (n=7 for each) were formed. Groups I and II were immunized enterally by OPV at the onset, 2 nd and 4 th weeks. Group II was also given S.boulardii in drinking water throughout the study. Group III was given only S.boulardii, while Group IV received no treatment. Two weeks after the last OPV dose, all the animals were sacrificed to obtain their kidneys for histopathological evaluation and all four groups were compared with respect to the severity of histopathological changes. While there was mild to moderate mesengial proliferation and widening, tubular atrophy, interstitial inflammation and fibrosis in Group I, no remarkable histological changes in the other groups were noted. Immunofluorescence microscopy revealed universal deposition of IgA and some C3 in Group I, while there was no IgA or C3 deposition in the other groups. Electronmicroscopy revealed mesengial proliferation along with matrix expansion, focal basement membrane thickening and electron-dense deposits in the mesengial area in only OPV group and the other groups were normal.

In conclusion, enteral S.boulardii administration prevented experimental IgAN development in mice. The aim was to assess the correlation of renal histopathological findings with clinical diagnosis in order to recognize the pattern of kidney diseases in our pediatric population. Methods: A total of 95 renal biopsies performed on children who presented to the Surgical Kidney Hospital in Damascus during a period of 3 years were retrospectively reviewed. Results: Nephrotic syndrome alone accounted for 52% of all cases, followed by hematuria in 21%, mild to moderate renal impairment including allograft dysfunction in 15%, nephritic syndrome in 10%, and HSP in 2%. The most common histologic lesion was MCD in (29%). FSGS was the second most common lesion (13%) followed by mesangial GN (11%), MPGN (9%), post-infectious GN (5%), IgA nephropathy (4%), membranous GN (3%), CNS of Finnish type (2%), Alport syndrome (2%), interstitial nephritis (2%), nephronophthisis (2%), HSP (2%), acute rejection (2%), chronic rejection (2%), nephrocalcinosis (1%), crescentic GN of undetermined origin (1%), and lastly, 5% were completely within normal limits. Familial and inherited diseases were encountered in 15%. Histopathologic diagnosis was mostly useful in nephrotic cases. While in hematuria cases, the usefulness of the histologic findings in terms of therapeutic and/or prognostic point of view was definitely less. One of the reason for that in our series is perhaps because we still do not have facilities to perform electron microscopic evaluation of the renal tissue. However, controversy about the usefulness of renal biopsy in such cases is still there. Conclusion: this study provides an important data on the pattern of pediatric renal diseases in our center and highlights the usefulness histologic findings in guiding the therapeutic plan especially for nephrotic children. Aim: The aim of this study was to determine the efficacy of tacrolimus in the management of SR FSGS in children. Study Design: This was a prospective study of 20 children with SR FSGS treated with tacrolimus (0.2-0.4 mg/kg per day in 2 divided doses over 12 hours adjusted to a trough level between 7-15ng/ml) for 12 months in combination with low dose steroids. Other therapies included angiotensin converting enzyme inhibitors, folic acid, multivitamins and lipid lowering agents. Results: The mean age at study entry was 11.1 years (range 5.6-16.8). The mean duration of nephrotic syndrome before initiation of tacrolimus therapy was 4.7 years (range 2.1-7.6). At the end of the treatment period 8 (40%) children were in complete remission, 9 (45%) children were in partial remission and 3 (15%) failed to respond. The average period of follow-up following cessation of tacrolimus treatment was 27.5 months (range 13.7-43.7). At last hospital follow-up 5 (25%) of children were in complete remission, 10 (50%) in partial remission and 2 (10%) in relapse. 3 children demised from dialysis related complications following cessation of tacrolimus treatment. Adverse events included sepsis (2), nausea (2) diarrhea (2), anaemia (4) and worsening of hypertension (4) . Conclusion: Tacrolimus is a safe and effective treatment for SR FSGS. However, like cyclosporine some children tend to relapse following cessation of treatment. It has been rarely reported in association with Graves-disease. Now we present a previously healthy 6-year-old Japanese girl who had proteinuria due to stage I MN and Graves disease. Patient: She was found to have 2+ proteinuria and a goiter at her school medical examination simultaneously. Serum free thyroxine was 4.98 ng/dl (normal range 0.95~1.74), thyroid-stimulating hormone (TSH) less than 0.003 microU/ml (0.34~3.88), anti-microsomal antibody 1600T (~100), anti-thyroglobulin antibody 400T (~100), and TSH-receptor antibody 84% (~10) consistent with Graves' disease. The electron microscopy finding of her renal biopsy specimen showed the presence of electoron-dense deposits located in the subepitherial and intramembranous spaces. With immunofluorescence microscopy, the bright granular staining of IgG along the gromerular capillary wall was found. These findings were characteristic of MN.

Objectives of study: To investigate whether Graves disease caused MN in this patient. Methods: We examined the presence of thyroid microsome and thyrogrobulin in glomeruli by immunofluorescence study using anti-thyroid microsomal antibody and anti-thyrogrobulin antibody.

Result: Glomerular granular staining of thyroid microsomal antigens was demonstrated corresponding to IgG granular deposits, but that of thyrogulobulin was absent. Conclusion: MN in this patient is presumed to be caused by immunecomplexes mediated by thyroid microsomal antigens. Objective: To explore the role of oxidative stress reaction on the injury of glomerular podocyte slit diaphragm molecular barrier. Methods: Thirty-two male Spraque-Dawley (SD) rats were randomly divided into control, low dose (3.0 mg/kg), nephrotic (7.5 mg/kg), overdose (10.0 mg/kg) groups by the dosage of adriamycin (ADR) injection.The levels of malondialdehyde (MDA) glutathione peroxidase (GSH-PX), hydroxy radical ( . OH) and superoxide dismutase (SOD) in renal cortex were measured; the expression of podocin was measured with immunohistochemistry. Results: (1) Compared with control group, the levels of MDA in renal cortex and 24-hour urinary protein were increased, the levels of SOD in renal cortex was decreased in ADR-treated groups, especially in nephrotic group (P<0.05). (2) in control group, podocin staining was a sable linearlike pattern along the capillary loops of glomerulus; In nephrotic group, podocin staining was a light tan discontinuous punctiform or short linear-like pattern along the capillary loops of glomerulus. Compared with control group, the score of podocin immunohistochemical staining was decreased in ADR groups, especially in nephrotic group (P<0.05). (3) There were some significant negative correlations between the score of podocin immunohistochemical staining and the levels of MDA in renal cortex. There were some significant positive correlations between the score of podocin immunohistochemical staining and the levels of SOD in renal cortex. Conclusion: (1) There was close relationship between podocin and the development of proteinuria.

(2) There were significant correlations between the reduction of podocin in glomerular podocyte slit diaphragm and oxidative stress reaction, especially lipid peroxidation. Lupus nephritis (LN) remains an important problem in patients with SLE. To evaluate the clinical course, histopathology and the efficacy and safety of high-dose pulse cyclophosphamide (CTX) in children with LN. Retrospectively, 25 children with LN were studied; all patients underwent renal biopsy and were followed up for at least 3 years. The clinical and serologic data at the time of renal biopsy were recorded. Five of them were excluded because of short period of follow-up or defective laboratory data. Based on renal biopsy (WHO classification for LN), 20 patients were treated with the following regimens: one patient (class I) with low-dose prednisolone (PRED), 7 (class II, III) with high-dose of PRED, 12 (class IV) with high-dose PRED and 13 received intermittent intravenous (IV) CTX pulses (monthly for 6 months, then every 3 months) followed by mycophenolate mofetil (MMF) as maintenance therapy. There were 13 girls and 7 boys. The mean age at the time of diagnosis of SLE was 10.2 years. Eighteen patients were more than 8 years old. Sixty percent of the patients were presented as nephritic-nephrotic syndrome. There was 1 with class I, 5 with class II, 2 with class III, 12 with class IV and none with class V based on biopsy. Eighty-five percent of cases went in remission, one was hemodialytic and 2 died due to renal failure and CNS involvement. Among 12 cases with class IV, 11 responded to PRED and IV CTX pulses. There was no evidence of side effects. It seems that IV pulse CTX does induce remission of clinical and renal disease in the majority of early diagnosed children with severe LN. Furthermore, it appears that MMF is an appropriate drug for maintenance therapy. However, this study was based on a small number of subjects. Further studies to confirm the long-term efficacy and safety of CTX pulse therapy on larger numbers of patients are needed. forming Group I were compared with 25 children on short course steroid therapy (ISKDC regime) (Group II). Children were examined for steroid side-effects and underwent blood tests, ophthalmologic evaluation and radiological examination. Results: Though remission was achieved in <4 weeks by 84% in group II against 60% in group I, the total dose received (25-50 mg/kg) was lower in group I (44% vs 20%). Forty-six % had 1-2 relapses, 44% had 3-6 relapses and 6% had 6-10 relapses. The proportion of children having >2 relapses was much higher in group II (60% versus 40%). Mean relapse/patient/ year was 1.6 (SD 0.5) in Group I against 3.1 (SD 1.6) in Group II. Delayed bone age (44%), radiological evidence of osteoporosis (42%). cushingoid facies (28%), posterior subcapsular cataract (16%), decreased growth velocity (14%) and hypertension (12%) were the side effects and were almost equally distributed in the two groups. More patients from Group II received a higher cumulative dose/ kg/year of >150 mg (76%versus 56% in group I) and these had higher risk for hypertension, delayed bone age and osteoporosis. Conclusion: Alternate day, prolonged therapy (Soyka regime) compared to short course, daily therapy (ISKDC) resulted in lower cumulative dose to the patient. Acute side effects and severity of infections were less. Mean relapse/patient/year were lower. Group II patients receiving higher cumulative dose had osteoporosis and delayed bone age. Objetive: To assess urinary protein excretion decrease in patients with primary SRNS treated with EC-MPS Methods: cohort of 13 patients, mean age: 9 years with primary SRNS. Inclusion Criteria: primary SNCR with of focal segmental glomerulosclerosis (FSGS). Exclusion Criteria: Glomerular filtration rate (GFR) 30% than baseline level, leukopenia, absence of decrease of proteinuria excretion by month 6 of treatment with EC-MPS. Mean time after the initial diagnosis of NS until the introduction of EC-MPS was calculated in patients who decreased urinary protein excretion below nephrotic range and in non-responsive patients and the glomerular damage, interstitial fibrosis and tubular atrophy were classified as: absent, mild, moderate, severe (0 to 3, risk grade>6). EC-MPS dosing: 450-700 mg/m 2 /day. Complete response was considered a reduction in the urinary protein excretion lower than or equal to 4mg/m 2 /hour; partial response: urinary protein excretion ranging from 4 to 40 mg/m 2 /hour and absence of response: urinary protein excretion in the nephrotic range. Laboratory monthly assessments: serum creatinine, urea, hemoglobin and blood cell counts, lipids, serum proteins, amilase, 24 hours urinary protein excretion. . No significant differences in the frequency of both alleles were observed among patients with different grades of hypertension or proteinuria. In conclusion, DRB1* 03011, and possibly 1105 alleles confer susceptibility to PSAGN. However the severity of the disease is not determined by these two alleles. Methods: fifty children who diagnosed as biopsy-proven FSGS were studied retrospectively by medical records. Response to treatment and pathologic slides, we compared normal renal function group (n=28) and decreased renal function group (n=22), assessed the factors affecting renal survival and progression to renal failure. Results: the mean age at onset was 8 1/12 years, gender ratio M: F was 2.3: 1 and the mean duration of follow-up was 7 1/12 years. The overall renal survival rate was 34% at 5 years, 8% at 10 years.

Five-year survival rate was 74% in normal renal function group, but 27% in decreased renal functin group. Between the two groups, there were no significant differences in age at onset, gender ratio, amount of proteinuria, incidence of hematuria, hypertension and mesangial hypercellularity. Decreased renal function group showed higher serum creatinine level, poor response to treatment, higher percent of glomeruli with sclerosis, moderate to severe tubulointerstitial change and vascular change (P<0.05). The prognostic factors of renal survival rate were same as above (P<0.05). There were no significant factor has shown relations with the progression rate to renal failure. Conclusion: we reviewed the factors affecting long-term outcome of FSGS. Serum creatinine level, steroid responsiveness and the degree of glomerulosclerosis were significant prognostic factors. But, age at onset, gender, amount of proteinuria, incidence of hematuria and hypertension were not considered as a prognostic factor.

A Background: Several studies have suggested that cyclosporine (CSA) and methylprednisolone pulse therapy (MPT) may be effective for idiopathic steroid-resistant nephrotic syndrome (ISRNS) in children; however, the optimal regimen has yet to be established. The present study evaluated the efficacy and safety of 2 years' treatment with CSA (Neoral) combined with MPT and prednisolone (PSL) in such patients.

Methods: In this prospective study, children with biopsy-proved ISRNS were enrolled. All patients received CSA and PSL (1 mg/kg every other day). Patients who had focal segmental glomerular sclerosis (FSGS) additionally received MPT (methylprednisolone at a dose of 30 mg/kg per day for 3 consecutive days at weeks 1, 2, 5, 9, and 13) . The dose of CSA was adjusted to maintain a trough level from 120 to 150 ng/ml for the initial 3 months, followed by 80 to 100 ng/ml for months 4 to 12, and 60 to 80 ng/ml for months 13 to 24. Results: Twenty-six patients were enrolled. Their mean age was 4.5±3.9 years. Two-year follow-up was completed in 22 patients. Histological examination at study entry revealed minimal changes in 16 patients, diffuse mesangial proliferation in 3, and FSGS in 7. At the end of the therapy, 19 patients had complete remission, including 6 who had occasional relapses of steroid-sensitive nephrotic syndrome, and 1 had partial remission; the remission rate was 90.8%. Nephrosis persisted in 1 patient. Disease progressed to end stage renal failure in 1 patient. Serial renal biopsy at the end of the study showed mild signs of CSA-related renal toxicity, including tubulointerstitial fibrosis in 2 (10.5%) of 19 patients. Conclusion: Combination therapy with CSA, MPT, and PSL for 2 years was clearly effective and produced a high remission rate without serious CSA-related renal toxicity in children with ISRNS, in contrast to previous reports. Objectives: Patients with hemolytic uremic syndrome who do not require dialysis in acute stage usually have a good prognosis. However the spectrum of renal compromise is wide. We believed non-anuric patients with higher creatinine values in acute stage could have different evolution when compared to patients with lower values. Aims: 1) To analyze the outcome after a 5 year and 2) To determine if peak serum creatinine values in acute stage would be a prognostic marker. Methods: 130 patients, aged 13.8 months at hemolytic uremic syndrome, were analyzed. They were classified into 4 groups: Group I, complete recovery; Group II had 2 subgroups: IIa, microalbuminuria, and IIb, proteinuria and/or high blood pressure, both with normal renal function; Group III, chronic renal failure; and Group IV, end stage renal disease. Peak creatinine value was definided as the highest value of at least 2 determinations in acute stage. These data were available in 57 patients and they were divided in those with creatinine equal to or higher than 1,5 mg/dl (26 patients) and those with lower values (31 patients). The relationship between creatinine and final outcome was analyzed. We applied Fisher's test.

Results: after a mean follow-up of 12 years, 83 patients were in group I, 27 in group IIa, 15 in group IIb (6 with hypertension, 5 with proteinuria and 4 with both) and 5 in group III. Eight out of 26 patients (30%) with creatinine equal to or higher than 1.5 mg/dl in acute stage and 1 out of 31 (3.2%) with lower values were in groups IIb and III in the last visit (p=0.007).

Conclusions: 1) after 12 years, 15% developed proteinuria, high blood pressure or chronic renal failure and 21% microalbuminuria. 2) Peak creatinine values in acute stage were a prognostic indicator. Objective of study: The aim of this study was to assess the serum concentration of hs-CRP in children with nephrotic syndrome (NS) treated with prednisone and cyclosporine A (CyA). Methods: Patients were divided into 3 groups: I -20 NS children (4-14 years) in relapse, examined twice: A -before treatment and B -after proteinuria regression (a 3-4 week course of prednisone therapy), II -20 children with steroid-dependent or steroid-resistant NS, treated with CyA, also examined twice: D -before treatment with CyA, E -6 months after therapy. Control group (C) consisted of 20 healthy children. Serum hs-CRP level was determined using a nephelometric method with Behring Nephelometer 100 Analyzer, Dade Behring. Results: It was shown that median hs-CRP concentration was the highest in children with relapsing steroid-sensitive NS before treatment (IA). After proteinuria regression (IB), the hs-CRP level decreased and did not differ from healthy controls (C) (p>0.05). In group II, before CyA administration (IID) the level of hs-CRP was normal, but increased after 6 months of treatment (IIE) up to a level six times higher that of the control group (p<0,01). Conclusions: In children with steroid-sensitive nephrotic syndrome in relapse, the serum hs-CRP level is increased but returns to normal values after a 3-4 week glucocorticoid treatment course. In children chronically treated with CyA due to NS, serum hs-CRP level increases significantly during the therapy. Slit diaphragm connecting adjacent foot processes of podocyte is the final barrier of glomerular capillary wall to prevent proteinuria. Both podocytes and neuronal cells are terminally differential cells and they share many common features. Nurexin is a presynaptic adhesion molecule that plays a role in synaptic differentiation, and they have been understood to be specifically expressed in neuronal tissue. We found that neurexins are expressed not only in neuronal cells but also in several organs including kidney. Our immunofluorescence study shows that neurexins are restrictedly expressed in glomeruli in kidney. Dual-labeling immunofluorescence studies show that neurexins are localized close to a CD2AP. We also detected some portions of neurexin staining are coincident with that of Rab3A, a synaptic vesicle associated molecule. We found that a single splice variant of neurexin-1 is expressed in glomeruli. The staining intensity of neurexin in the glomeruli clearly reduced and their staining pattern shift to more discontinuous patchy pattern in puromycin aminonucleoside nephropathy and anti-nephrin antibody induced nephropathy. The alteration of neurexin in these models was detected more clearly and rapidly than nephrin. We confirmed that neurexin is expressed in podocyte also in human kidney section. These observations suggest that neurexin is involved in the development of proteinuria and that neurexin could be an early diagnostic marker of podocyte injury. To further elucidate the clinical relevance of T-cell abnormality in minimal change nephrotic syndrome (MCNS), and to predict the consequences of MCNS, we studied T-cell receptor (TCR) diversity by analizing CDR3 size distribution and the frequency of V repertoire usage. Thirty-six pediatric patients with MCNS were enrolled. Eighteen were frequent relapsers and/or steroiddependent (FR/SD) and 18 were non-frequent relapsers (NFR). The study was performed to analyze serial changes of TCR V repertoires in the two groups of patients. Frequencies of V repertoire usage were determined by flowcytometry, and TCR CDR3 length distribution was analyzed by GeneScan.

In NFR patients, abnormalities in the distribution of 21 V repertoires were few in both CD4 + and CD8 + T cells. In FR/SD patients the patterns were normal in CD4 + T cells, while selected V repertoires were significantly increased in CD8 + T cells in some patients. Furthermore, TCR diversity was significantly reduced in both CD4 + and CD8 + T cells in FR/SD patients as shown by marked skewing of CDR3 size distributions. It is noteworthy that in some FR/SD patients the initially abnormal TCR diversity improved as the clinical symptoms improved such that they became NFR over the years. Analysis of TCR diversity may delineate the subgroup of patients with FR/SD and provide a rationale for early intervention with immunosuppressive therapy for these patients. Background: Transforming growth factor-β is known to play a role in the interaction between metabolic and homodynamic factors in mediating accumulation of extracellular matrix in the diabetic nephropathy. TGF-β1 gene polymorphism was associated with circulating TGF-β levels and influenced the pathogenesis of fibrotic diseases including diabetic nephropathy. In this study, we examined the relationship between TGF-β1 gene codon 10 polymorphism and type 2 diabetic nephropathy with more than 10-year history of disease. Methods: We conducted a case-control study, which enrolled 325 type 2 diabetes. A total of 176 patients with diabetic nephropathy were compared with 149 patients without diabetic nephropathy. TGF-β1 codon 10 genotyping was determined using polymerase chain reaction with sequence specific primers method.

Results: Distribution of TGF-β1 codon 10 genotype in the patients either with nephropathy or without nephropathy is confined to Hardy-Weinberg equilibrium. Methods: NZB/W F1 female mice were distributed into three experimental groups (n=5 per group) according to age: 3, 4.5 and 6 months. At specific time-point for each group, 24-hour urine and blood samples were collected to determine proteinuria, osmolality and creatinine levels. After sacrifice, kidneys were removed to measure chemokines and cytokines levels by ELISA (pg/100 mg of tissue). Results: Urinary flux was significantly lower at 4.5 than at 3 and 6 months. A significant reduction in creatinine clearance and an increase in proteinuria were detected at 4.5 and 6 months when compared to 3 months. No significantly changes were observed in serum and urinary osmolality. Regarding inflammation, MCP-1 significantly increased at 4.5 (262.7±50.5) and remained elevated at 6 months (334.6±87.7) when compared to 3 months values (206.6±37.9). KC was also higher at 6 than at 3 months ( Background: Nephrotic syndrome (NS) is related to immunological factors and renal inflammatory mechanisms. Many studies showed that inflammatory mediators, especially interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), have a role in kidney injury. Changes in their urine concentration were found in lupus nephritis and IgA nephropathy. Thus, the aims of this study were to evaluate IL-8 and MCP-1 in serum and urine samples of pediatric patients with primary NS and to verify the relation between these measurements and protein excretion. Methods: Patients were divided according to current 24-hour proteinuria into two groups: lower than 200 mg/24 hours (group 1, n=11) and higher than 200 mg/24 hours (group 2, n=14). Blood and 24-hour urine samples were collected and stored at -80 °C. IL-8 and MCP-1 were measured by ELISA standard methods.

Results: Blood IL-8 and MCP-1 did not differ between the groups. Urinary IL-8 levels (pg/mg of creatinine) were significantly elevated in patients of group 2 when compared to group 1 (51.06±9.67 vs. 20.48±5.24, p<0.05). Although group 2 also exhibited higher values of urinary MCP-1 (223.3±66.64 pg/mg creatinine) than group 1 (151.1±31.64 pg/mg creatinine), they did reach statistical difference. Conclusion: The inflammatory process in NS seems to be a local phenomenon, since blood levels of these chemokines were similar in all groups. Moreover, our findings showed a relation between IL-8 and the presence of proteinuria and suggested a role for this local inflammatory mediator in disease activity.

The Characteristics of IgA Nephropathy Detected in School Urinary Screening IgA nephropathy (IgAN) is one of common types of glomerulonephritis in children. However, progression to ESRD in patients with IgAN is not as rare as originally thought. In Korea, school urinary screening (SUS) program, an useful tool to find out abnormal urinary findings, initiated in 1998. IgAN was the most common histopathological change in children with isolated hematuria and/or proteinuira in SUS. We studied to clarify the clinical and pathologic characteristics of IgA nephropathy detected by SUS in Korea. We investigated 35 patients (symptomatic group=14 vs SUS group=21) had been diagnosed with IgAN following renal biopsy at the Yeungnam Univ. Hospital between May 1998 and May 2004. These patients were analyzed clinical nature, laboratory data and histopathologic findings (Haas classification in LM) and progress, retrospectively. Their mean age were 10.3±2.5 and 9.5±3.6, respectively, at the time of kidney biopsy. Gross hematuria and edema apt to be common in symptomatic group. There were no significant difference in serum IgA level, estimated Ccr, 24-hours protein amount, light microscopic class and electron microscopic findings between two groups. Mesangial IgA deposition was significantly more intense in symptomatic group with gross hematuria. In addition to IgA deposition in capillary and immune dense deposition in intramembrane is significantly common in symptomatic group with nephrotic range proteinuria. However, progression to chronic renal failure was not noted in both groups during 32.2±28.8 and 24.8±11.2 months respectively. Also there were no difference in outcome according to treatment modalities. A longer follow-up period is needed to obtain more information on progression of IgAN with nephritic range proteinuria by disclosing IgA deposition in capillary and immunedense deposition in intramembrane. Outcome of SRNS is uncertain and especially patients unresponsive to treatment have a high risk to develop ESRD. Prognosis has improved with the introduction of CSA, however but long-term follow-up data are scarce and response to CSA in patients with genetic forms of SRNS is uncertain. We report on 25 patients with SRNS, that was diagnosed at a median age of 3.6 (range 0.5-11.2) years. Treatment with CSA was initiated on concomitant prednisone therapy, however steroids were discontinued after due course in all patients. Median follow-up is 9.5 (0.3-19.1) years. 17 patients had FSGS on renal histology and 12 patients had MCNS. Complete remission (CR) was defined as reduction of proteinuria <100 mg/m 2 /d. Partial remission (PR) was defined as reduction of proteinuria of at least 50% and cessation of edema with serum albumine levels >25g/l. Results: 12 patients (6 FSGS, 6 MCNS) reached CR with CSA treatment. In 8 of these (5 FSGS, 3 MCNS) CSA could be tapered and discontinued successfully after a median time of 2 (0.5-6.1) years. Eight patients showed (7 FSGS) a PR while 5 patients (3 FSGS) showed no repsonse (NR). Of 6 patients going into ESRD 5 had podocin mutations (PM). Only one patient with PM showed partial remission on CSA. Our data indicate a positive effect of CSA treatment in SRNS, especially in sporadic cases. In patients with CR tapering and even discontinuation of CSA is possible. Prognosis of SRNS has improved with CSA treatment. Objective: We planned to investigate the effects of RSV on the proteinuria and glomerular structure of rats and to explore the role of RSV in the pathogenesis of minimal change nephrotic syndrome. Methods: SD rats were inoculated with 6 10 2 , 10 4 , and 10 6 PFU RSV respectively, and sacrificed on days 4, 8, 14, 28 and 60 postinoculation (RSV 4 , RSV 8 , RSV 14 , RSV 28 , RSV 60 ). Renal histology was observed by light microscopy and electron microscopy. Meanwhile, the proteinuria and serum parameters were measured. The RSV RNA and RSV titer were determined by in situ hybridization and plaque assay respectively. Immune complex deposits were detected by immunofluorescence microscopy. Results: After inoculation, the urinary protein excretion was increased, especially in 6 10 6 PFU RSV 14, 28, 60 (P<0.05). The serum albumin of 6 10 6 PFU RSV 14, 28, and different-titer RSV 60 decreased, but no significant differences in cholesterol, urea nitrogen and creatinine were found among all. Slight hypercellularity in minority glomeruli and swelling of partial tubular epithelial cells were observed in RSV 4, 8 of different-titer, whereas a relief of the above changes and no abnormalities were detected in RSV 14 and RSV 28 respectively under a light microscopy. Extensive foot process effacement was observed in 6 10 6 PFU RSV 14, 28, 60 under an electron microscope. RSV RNA signal and RSV titer of renal and pulmonary tissues, depending on the dose of inoculum, reached their climax on day 8 postinoculation, especially in 6 10 6 PFU RSV 8 . No immune complex deposits were detected in the renal tissues. Conclusion: Our study reports for the first time that RSV can lead to nephropathy in rats on day 14-60 postinoculation, especially in 6 10 6 PFU RSV-inoculated rats, which may be a new exploration of the pathogenesis of MCNS. Objectives of study: Podocytes play an important role in maintaining the glomerular filtration barrier structure and functions, which associates with several podocyte-specific proteins. Our previous study indicated the antiproteinuric effects of dexamethasone were achieved by changes the expression of certain podocyte molecules in vivo. The extracellular signal-regulated kinases regulates a wide range of cellular processes. The aim of the present study is to analyze the potential effects of dexamethasone on podocytes in vitro and to investigate its associated signal transduction pathway.

Methods: Immortalized mouse podocyte clone was divided into three groups: the dexamethasonetreated group (Dex-group), the dexamethasone with puromycin aminonucleoside-treated group (Dex-PANgroup), and control. In Dex-group, cultured podocytes were treated with dexamethasone, while in Dex-PAN group, cells were treated with dexamethasone for 30min first, then added puromycin for different time periods. Changes of the protein expression of podocyte-specific proteins and phosphorylation of ERK were analyzed by Western blotting analysis.

Result: Compared with the control group, in Dex-group, the expression of nephrin, podocin, CD2AP, α-actinin4 proteins and VEGF protein started to elevate at 24 hr, while neph1 showed no obviously change. ERK signaling pathways was activated. Increased phosphorylation of ERK was marked but transient, which increased from 2 min to 15 min, then decreased. At 30 min the level of phosphorylation of ERK returned to the baseline. The phosphorylation of ERK level was significant raised in Dex-PAN group, and lasted to 60 min. Conclusion: Dexamethasone alters the expression of certain podocyte-specific proteins not only in vivo but also in vitro, and in part, through the activation of the ERK signal pathway.

KH. Kim Minimal lesion in the renal biopsy of idiopathic nephrotic syndrome (NS) patients (pts) generally predicts a benign course. FSGS lesions in NSpts, on the other hand, are associated with increased risk of steroid resistance and progression to renal failure. FSGS may be observed in follow-up biopsies despite being initially undetectable. Whether this represents sampling error or the true natural history of this condition, earlier markers of steroid resistance and poorer prognosis could prove helpful. Renal morphometric analyses was performed in 13 NS pts, ages 2 to 19 years, initially diagnosed with minimal lesion, with (N=8) or without(N=5) subsequent progression to FSGS or end stage renal disease (ESRD), along with 5 controls ages 3 to 16 years. The age of patients in progressive and non-progressive group and controls were similar. GBM width in patients with minimal lesion (368±52 nm) who subsequently progressed, was significantly greater than that in non-progressive group (290±35 nm, p<0.02). GBM width in both groups was not significantly different compared with the controls (321±49 nm). Average foot process width was increased in patients both with progression and non-progression as compared with controls, but there was no significant difference between progressive and nonprogressive group. The length density of podocyte detachment per GBM surface was not significantly different between progressive, non-progressive groups and control groups. There were no significant differences in the mean glomerular volume and cortical interstitial volume fraction between progressive and non progressive group.

In conclusion, GBM width may help to differentiate between progressive and non-progressive groups in minimal lesion nephropathy. This may be a pathogenetic clue and needs further study. Objective: Our study is to investigate the correlation between clinical features and pathological characteristics on Henoch-Schönlein purpura nephritis (HSPN) and the therapeutic methods. Methods: Fifteen boys and five girls aged 7-15 years (median 10.5 years) with HSPN were analyzed retrospectively. The clinical characteristics, laboratory data, pathological findings and therapeutic methods were investigated. Results: The patients with isolated hematuria and isolated proteinuria, the pathologic patterns were lighter then gradeII b ; eight patients with hematuria and proteinuria and seven patients with nephrotic syndrome, the pathologic patterns of injury is more severe then gradeII b , whose pathologic patterns injury exceeded gradeII b is 77.8%. Twelve patients with nephritic-range proteinuria (>50mg/kg.d) and nephrotic syndrome received corticosteroids, cyclophosphamide, heparin and dipyridamole treatment. Nine of twelve patients received intravenous pulse methylprednisolone (MP) and pulse cyclophosphamide (CTX). Fourteen of twenty patients obtained stable remission after 3 months to 5 years, and five of twenty patients have asymptomatic microscopic hematuria, another one only has minimal proteinuria. Conclusions: If the clinical features showed nephritic-range proteinuria or nephrotic syndrome, the renal pathologic changed markedly as well. For patients whose pathologic exceeded grade III b or have renal tubule and interstitial damage, our study suggests that MP pulse therapy have satisfied curative effect. Materials and methods: in experiment 1, HIGA mice, C57BL/6 mice and Balb/c mice were inoculated intravenously with live CB4 and inactivated CB4 once a month from 1 to 12 mo of age. In experiment 2, HIGA mice, C57BL/6 mice and Balb/c mice were inoculated intravenously with live CB4 and inactivated CB4 once at 6 wk of age. Mice in the control group were inoculated with vehicle. The kidneys were extirpated from 5 mice of each group killed with time after inoculation for histological evaluation. Experiment 3: we examined prostaglandin (PG) synthetic activity of cultured human mesangial cells.

Results: the scores for mesangial IgA deposition, PCNA-positive and matrix scores at 20 weeks were higher in HIGA mice with live CB4 than in HIGA mice with inactivated CB4 or without CB4. On EM examination, swelling and detachment of endothelial cells from 24 hours after inoculation and increase of serum IFN-gamma concentration were found in mice with live CB4. The scores for mesangial IgA and IgG depositions, PCNA-positive and matrix scores at 30 weeks were more frequently found in Balb/c mice with live CB4. Production of PGE2 and TXB2 significantly increased in cultured human mesangial cells damaged by live CB4. Conclusion: these results suggest that CB4 provokes exacerbation of renal pathological findings in HIGA mice via endothelial injury and IFN-gamma production, and may play important roles in IgAlike glomerulonephritis pathogenesis. Rapidly progressive glomerulonephritis (RPGN) is a rare occurrence in Alport syndrome (AS). This report describes the case of a 10-year-old malewith AS who developed RPGN and considers the cause of RPGN in this patient. He had a history of persistent hematuria and proteinuria since birth. At the age of 2 years, he was diagnosed with AS based on a renal biopsy. He developed nephrotic syndrome at the age of 5 years. Before administration of cyclosporine (CyA), repeated renal biopsy was performed at the age of 7 years. The biopsy specimen showed pathologic lesions characteristic of AS without crescents. Using immunofluorescence (IF) staining, the expression of alfa-5 chains of collagen IV was found to be absent in the glomeruli. Therefore, CyA was administered for eight months. Although he recovered from nephrotic syndrome, the effect of CyA was limited. After the cessation of CyA, his renal function slowly exacerbated. At the age of 9 years, the administration of angiotensin receptor blocker was started. No subsequent anti-proteinuric effect was noted and his renal function improved to Cr 0.79 mg/dl. However, by the age of 10 years, he showed macrohematuria and acute deterioration in renal function to Cr 9.38 mg/dl. Subsequently, he underwent a third renal biopsy. On light microscopy, the biopsyspecimen showed diffuse cellular crescentic glomerulonephritis. If findings indicated pauci-immune type and electron micrography showed a few subepithelial deposits. A serological study revealed negative results for MPO-ANCA, PR3-ANCA, and anti-glomerular basement membrane antibody. Despite immediate treatment with pulses of methylprednisolone, cyclophosphamide, and plasma exchange, he progressed to end stage kidney disease. The patient reported here presents either a super imposition of RPGN upon a preexisting case of AS or a new morphologic and clinical presentation for AS. The WT1 gene encodes a zinc finger transcription factor involved in kidney and gonadal development. Mutations of the WT1 gene have been shown to cause Denys-Drash syndrome (DDS) and Frasier syndrome (FS). The association of early onset nephrotic syndrome progressing to renal insufficiency, XY pseudohermaphrodism and Wilms' tumor characterizes DDS. Renal biopsy shows diffuse mesangial sclerosis (DMS). FS is also characterized by XY pseudohermaphrodism and nephropathy, but patients have delayed kidney failure characterized histologically by FSGS. This report examines three girls with nephrotic syndrome related to mutations in the WT1 gene, but with normal female karyotype and development. Two girls with early-onset steroid-resistant nephrotic syndrome presented classical WT1 mutations coding for an amino acid change (D396N) and (R394W) at exon 9 that is typical of DDS. Both children were phenotypically and genotypically females. They developed end stage renal failure within 7 years. One girl had a Wilms' tumor on the right kidney. The third child was identified with heavy proteinuria at 7 years of age. Laboratory investigations revealed a protein level of 7.2 g/dl (6-8 g/dl), albumin 3.7 g/dl (3.9-5.3 g/dl). Proteinuria worsened to 4 g/24 h and she failed to respond to prednisone. Renal biopsy demonstrated FSGS in 20% of glomeruli. The splice site mutation IVS9+4 G >A, known to be associated with FS, was found in this patient. Karyotype was 46, XX and she had normal uterus and adnexae on ultrasound. Angiotensin-converting enzyme inhibitors were prescribed but she still has heavy proteinuria without renal failure. The classical clinical presentation of DDS and FS is out dated. Pediatric nephrologists need to consider the possibility of these genetic syndromes in evaluation of females with steroid-resistant nephrotic syndrome. We aimed to compare the effects of Cyclosporine (CsA) or MMF with or without combination of vitamin A,D,E or N-acetyl-L-cysteine (NAC). The study included 64 rats in eight groups: control, nephrotic syndrome without treatment, treatment with CsA, MMF, vitamin A,D,E, combination of CsA and vit ADE, combination of MMF and vit ADE and combination of NAC and vit ADE. All rats except the control group were given Adriamycin. Blood samples were drawn and 24-h urine were collected on day 1 and at weeks 5 and 16. At the 5 th week, 24-h urinary protein excretions in the treatment groups were higher and serum albumin levels were lower than that of 0 th week and control groups (p>0.05). At the 16 th week, urinary protein excretions in group CsA&ADE was lower than of the groups of CsA, MMF, MMF&ADE, ADE and NAC&ADE with non-significance (p=0. 42, p=0.94, p=0.72, p=0.82, p=0.53) . Serum albumin in group MMF&ADE and group ADE were significantly higher than of control group (p=0.015, p=0.01). Serum albumin in group ADE was significantly higher than that of groups of CsA and CsA&ADE (p=0.05, p=0.045). Serum triglyceride in group MMF&ADE was significantly lower than that of groups CsA and CsA&ADE. Serum creatinine in group MMF&ADE was lower than that of the groups of CsA, CsA&ADE, MMF, ADE and NAC&ADE and was significantly lower than that of control group (p=0.004). Serum creatinine in group CsA was significantly higher than of groups of CsA&ADE, MMF, MMF&ADE (p=0.004, p=0.001, p=0.001, respectively). In group NAS+ADE, total oxidant was significantly higher and total anti-oxidant was significantly lower than other treatment groups (p<0.05). We showed that the better effect on proteinuria, serum triglyceride and albumin and lower serum creatinine by adding vitamin A, D, E in the treatment of experimental nephrotic syndrome with CsA or MMF. Conclusion: HT is associated with known risk factor of progression of biopsy-proven GN such as S-Cr or proteinuria. The CRB is an important tool for studies focusing on the epidemiology of GN in the Czech Republic and serves as a basis for cooperation in this field. (4), lupus-nephritis (3), IgA-nephropathy (2), minimal change disease and membranous nephropathy (by 1) were observed. The distinction of morphological variants of the FSGS was started recently (last 6 months). Among the patients with FSGS, which were biopsied during this short period (4), all have had a tip-lesion. These patients were started cyclosporine A 150 mg/m 2 /day with complete (3) and partial (1) remission achievement after 1-3 months. Thus, the focal and segmental glomerulosclerosis is the most frequent cause of the nephrotic syndrome in children. The focal and segmental glomerulosclerosis with tip-lesion is characterized by favourable course and good response to therapy with cyclosporine A during the short-time period. Objectives of study: Molecules of monocyte chemoattractant protein-1 (MCP-1), β-catenin and cytokeratin19 (CK19) express increased in cellular crescent, which is a severe pathological change in renal diseases. However, it is unknown whether these molecules in urine correlate to the number or extent of cellular crescents. Methods: Urinary molecules mentioned above were detected in 20 healthy subjects and 124 patients with renal diseases by ELISA. The expressions of these molecules and macrophage (CD68 positive) in 87 biopsy specimens were also investigated. Results: Significant higher levels of these molecules in urine were demonstrated in all patients with renal diseases compared with healthy subjects (p<0.01), but the highest level in patients of the cellular crescent group. The significant correlations were revealed between these molecules in urine and the index of cellular crescents (r=0.75, r=0.21, r=0.63, p<0.01), between these molecules in glomeruli and the index of cellular crescents (r=0.58, r=0.66, r=0.52, p<0.01), and between these molecules in glomeruli and in urine (r=0.62, r=0.50, r=0.20, p<0.01).

Conclusions: This study suggested that the detection of urinary MCP-1, β-catenin and CK19 might become potential biomarkers for clinical diagnosing cellular crescent lesions and assessing cellular crescent extent in renal diseases. This study aims to evaluate the benefits and harms of levamisole in steroid dependent (SD) and frequent-relapsing (FR) nephrotic children. Material and methods: A total of 24 steroid-sensitive nephrotic children were recruited prospectively from January 2004 to December 2006. 5 females and 19 males, 11 (48%) FR, 12 (52%) SD. Mean age at the beginning of levamisole was 5,7 years. Twelve didn't receive any alternative drug before, 12 received cyclophosphamide. Renal biopsy was perfomed in 5 patients, 4 had Minimal Change Disease (MC), one patient had MC at the first biopsy and FSGS in the second. The patients were divided in two groups according to their steroid response: SD and FR.

Levamisole was started at a dose of 2,5 mg/kg/48 h as a second line drug in order to try to prolong periods of remission. Clinical and laboratorial controls were performed monthly. Patients were evaluated as: total responders: when steroid withdrawal was possible, partial responders: when steroid reduction was possible, non-responders: no steroid modification in 3 months. The responders used levamisole for one year.

Results: The response of frequent-relapsing patients was: 63% of total response, 18% of partial response and 18% of non-responders. Steroid-dependent patients had 50% of total response, 25% partial and 25% non-responsers. Only one patient developed leukopenia. Now 21% (5) are out of levamisole and in remission, 50% (12) are still using levamisole(alone or low-dose of prednisone), 21% (5) are using cyclosporin, one used cyclophosphamide and one is using low-dose prednisone. Conclusion: Levamisole is a promising alternative drug for nephrotic syndrome. The major advantage of levamisole is its steroid-sparing effect with minimal toxicity. Conclusions: Hypertension and renal insufficiency were less frequently seen in Chinese children with FSGS, isolated hematuria as unique clinic presentation was common in FSGS. All pathological variants had tubular-interstitial lesions, but vascular lesions were rarely seen. Most FSGS children with nephrotic syndrome were sensitive to steroid at initial stage, and easy to develop frequent relapse gradually, immunosuppressive agent may be helpful to elevate remission rate. The aim of the study was to assess whether the serum index IgA/C3 can be a usefull marker of activity IgAN and HSN in children. Twenty children with IgAN (mean age 10.0±3.6 years) and 33 children with HSN (mean age 9.53±4.17 years) were retrospectively analysed. In all children urine analysis, GFR were checked and the levels of serum IgA and C3 were measured before therapy, serum IgA/C3 was than calculated. At the onset of illness, IgAN and HSN was diagnosed based on the renal biopsy in mean time 1.06±1.37 years. Changes in light microscopy were graded I-V according to the classification of WHO (cWHO). All biopsies were scored for activity and chronicity index (AI max score 9, CI max score 12) (Pediatr.Nephrol.1989,3,248 Heparan sulfate proteoglycans are present both as structural components of the GBM and as modifiers of growth factor signaling on the cell surface. In MCNS the presence of certain HS epitopes inthe GBM is decreased. hSulf1 and hSulf2 are recently identified endosulfatases, that can remodel the sulfation pattern of HS and thereby control the availability and presentation of factors such as FGF and HGF to their high affinity receptors. Sulfatase activity requires posttranslational modification by formylglycine-generating enzyme or sulfatase modifying factor 1 (FGE/SUMF1) that is counteracted by its paralogue pFGE/SUMF2. We demonstrated that podocyte, endothelial and tubular epithelial cell lines express mRNA for Sulf1, Sulf2, SUMF1 and SUMF2. We investigated the in vivo distribution patterns of these enzymes in human kidney specimens by in situ hybridization. In histologically normal kidneys (n=5) expression of hSulf1 mRNA was largely restricted to peritubular and glomerular endothelial cells, where as hSulf2 mRNA was weakly expressed in all glomerular resident cell types. Expression of SUMF1 and SUMF2 mRNA was present in a minority of mesangial cells and podocytes, as well as in avariable number of glomerular and peritubular endothelial cells and invascular smooth muscle cells. In MCNS (n=5), the glomerular expression patterns of hSulf1, SUMF1 and SUMF2 mRNA did not differ significantly from that in controls. In contrast, hSulf2 mRNA expression was increased in podocytes. Increased hSulf2 expression by podocytes is a novel factor to be considered in the pathogenesis of MCNS. The onset and duration of INS, histopathological changes in renal biopsy, results of corticosteroid therapy and proteinuria selectivity reflecting the alteration of glomerular capillary wall were analysed. Materials and methods: 80 children with INS aged 2-18, followed up 12 to 36 month, and 20 healthy children were studied. In all patients 1 stage of CKD were diagnosed. INS children were divided in two groups regarding to serum cystatin C levels as a marker of GFR: group I (n=37)children with unchanging GFR, II (n=43) -patients with impairment renal function over the study period. Serum total protein, albumin, cholesterol, cystatin C, creatinine and immunoglobulin IgG, and urinary protein, albumin, IgG and creatinine were measured. Results: Serum cystatin C levels were higher in both groups of INS patients compared to healthy children (gr. I: 0.8±0.11, gr. II: 1.19±0.42 vs 0.7±0.1 mg/l; p<0.01). In group II amount of 24-hour proteinuria was significantly higher than in group I (2.93±2.27 vs 3.76±2.79 g/l; p<.001), however other biochemical parameters (including IgG excretion, albuminuria, selectivity index) were not different. In group II higher age of onset was found. In this group mesangial proliferation and focal segmental glomerulosclerosis more often were observed. Conclusions: The age of onset, histopathological diagnosis and proteinuria can be considered as important markers of CKD progression in children with INS. Probably, longer follow-up of children with INS is necessary to find other prognostic factors.

K. Kilis-Pstrusinska, K. Fornalczyk, D. Zwoliñska

Cyclosporine A (CsA) has been used as a therapeutic option for steroid-dependent and steroidresistant nephrotic syndrome (NS). The aim of the study was to assess the effects of long term CsA treatment in children with NS. Methods: We performed retrospective study to evaluate safety and efficacy of CsA therapy in 44 children with NS (20 girls and 24 boys), aged 2-16 years. Results: Before introducing CsA, in 30 patients steroid-dependent NS and in 14 -steroid-resistant NS were observed. 28 children presented symptoms of steroid toxicity. Pre-treatment renal biopsy was performed in 42 patients (2 children without biopsy because of renal agenesia). Minimal change disease was diagnosed in 18 (43%) children, focal segmental glomerulosclerosis (FSGS) in 9 (21%), mesangial glomerulonephritis (GN) in 8 (19%) and membranoproliferative GN in 7 (16%) cases. All children were taking CsA (target blood trough levels 50-150 ng/ml) more than 6 months, mean 24 months (range 7-72). Complete remission was achieved in 32 (73%) children, partial in 9 (20%). In 17 (39%) patients CsA treatment was continued with mild dose of steroids. 3 patients (7%) did not respond to the therapy and one of them end stage renal failure developed. Following side effects have been observed: hyperuricuria (20% of patients), hyperuricaemia (9%), hypomagnesaemia (7%), hypertension (11%), hypertrichosis (9%), gingival hyperplasia (5%), hepatotoxicity (2%), gastritis and ileitis symptoms (2%). In 15 patients control renal biopsy was performed after 24-36 months of CsA therapy. In 4 patients progression to FSGS was seen. Only in one case histological findings of CsA nephrotoxicity occurred. Conclusion: Long-term CsA treatment in children with steroid-dependent and steroid-resistant nephrotic syndrome can be consider as an effective and safe therapy.

Introduction: Membranous nephritis represents a rare disease in childhood with an incidence of 0.8 to 6% in renal biopsy specimens among various types of glomerulonephritis. Although in many cases the disease is considered as idiopathic the association of membranous nephritis and infectious agents it is also well known. Aim: We report a case of a 19 months old baby girl of Asian origin, presented with macroscopic haematuria of glomerular origin, proteinuria, 1-3 gr/24 hours, hyaline and granular casts, maculopapular rash on the legs and microcephaly. Methods: Renal function tests in terms of plasma urea and creatinine were normal. The renal biopsy showed membranous nephritis. Tests for infectious diseases (TORCH screen) showed a primary CMV infection. This diagnosis was based on the presence of high level CMV specific IgM antibodies, increased IgG antibodies and low avidity of CMV specific IgG antibodies. A real-time-PCR of the renal biopsy specimen was positive for CMV as well, confirming this virus as the causative agent of membranous nephritis in the presented case. Treatment with Gancyclovire per os was introduced and it was most impressive since proteinuria disappeared in the following two to three weeks. Two years after the diagnosis the child remains well and asymptomatic.

In summary: To our knowledge, among various infectious agents, there is no case of congenital or secondary nephropathy described so far due to CMV infection in children. Objective of study: Pulse methylprednisolone therapy (PMT) has been shown effective in proteinuric renal diseases. But its exact effect in children with steroid-sensitive relapsing nephrotic syndrome still has no definite conclusion. To evaluate the effect and adverse effects of PMT, we performed a retrospective study. Methods: There were 11 cases of steroid-sensitive relapsing nephritic syndrome received PMT. They all had been treated with oral prednisone in similar condition previously. A self control design was used to compare the effect of PMT and oral prednisone. Results: The average age was 7.5±3.1 years. Ten cases attained complete remission after the first course of PMT, and the average duration of PMT until remission was 7.4±4.4 days. One case attained complete remission after the second course of PMT. Compared with the effect of oral prednisone previously, seven cases attained complete remission more rapidly. Paired-samples t-test was performed to compare the effects of PMT and oral prednisone in six cases with very similar state, however, the difference between them was not significant (p=0.082). During the treatment of PMT, adverse effects were found in 6 cases. Conclusion: Compared with oral prednisone, the superiority of PMT had not been definitely confirmed, and adverse effects might appear during the treatment. Therefore we should be very strict with administering PMT in children with steroid-sensitive nephrotic syndrome. The study we performed was retrospective, so it was necessary to design a prospective clinical randomized controlled trial to further evaluate its effect. Objective of study: Pulse methylprednisolone therapy (PMT) has been shown effective in proteinuric renal diseases. But the exact effect of PMT in children with steroid sensitive nephrotic syndrome (SSRN) still has no definite conclusion. To evaluate the effect and adverse effects of PMT, we performed a prospective study. Methods: A prospective clinical randomized controlled trial was conducted to compare the effect and adverse effects of PMT with oral prednisone (OP) in children with SSRN. Thirty-one children were enrolled with only 23 suitable for evaluation including 9 patients in the PMT group and 14 in OP group.

Results: There was no significant difference between both groups in complete remission rate. The average durations of therapy until remission were 4.9±1.5 days in PMT group and 9.6±6.3 days in OP group, respectively. Complete remission was more rapidly attained in PMT group (p=0.036; <0.05). During the treatment and the following 3 months, no significant difference of adverse effects was found between both groups. There was no significant difference between both groups in relapse rate during 3 months follow-up. Conclusion: Compared with oral prednisone, PMT could induce complete remission more rapidly and did not company with more adverse effects in children with SSRN. PMT had no effect on the reduction of relapse rate in the following 3 months after administration.

Outcome of Childhood Henoch-Schönlein Purpura Nephritis with Nephroticrange Proteinuria in a Single Center Objective: The majority of children with Henoch-Schönlein purpura nephritis (HSN) only with hematuria and/or mild proteinuria have good chances for recovery. However, it is still unclear how we should treat HSN with persistent massive proteinuria. The aim of this study is to evaluate the outcome of childhood HSN with nephrotic-range proteinuria treated with angiotensin converting enzyme inhibitor (ACEI) and corticosteroids. Methods: 109 patients with Henoch-Schönlein purpura (58 boys, 51 girls) ranging from 0.5 to 13.8 (6.3±2.7) years old at onset visited our hospital between April 1997 and December 2006. Thirty seven (33.9%) developed HSN. Mean age of 21 (13 boys, 8 girls) HSN patients with nephroticrange proteinuria (>40 mg/h/m 2 ) at the time of diagnosis was 8.3±2.9 years old. Two developed nephrotic syndrome, but none had renal insufficiency at onset. One patient suffered moderate proteinuria and renal dysfunction 8 years after the onset. Renal biopsies were done in 16 cases and showed 1 for grade I, 4 for grade II and 10 for grade III respectively (classification by International Study of Kidney Diseases in Children). Results: Eleven of the 21 patients received ACEI and no patients were treated with immunosuppressive agents except for corticosteroids and methylprednisolone pulses. After a mean follow-up of 3.8 years, 11 patients showed complete remission, 9 had mild proteinuria or microscopic hematuria, only one postpartum patient presented with nephrotic-range proteinuria, and none developed renal insufficiency. Conclusions: Our results suggested that the short-term outcome of childhood HSN with nephroticrange proteinuria but not renal insufficiency was relatively favorable. Thus, the degree of proteinuria is not a sole prognostic factor for childhood HSN. Therefore, the indication for corticosteroid therapy should be clarified. Recent observations determined a R1160X specific exon 27 mutation in the gene encoding nephrin (NPHS1) which evidenced an unexpectedly mild Finnish-type congenital nephrotic syndrome (CNS) phenotype. The long-term follow-up of patients with this mutation is actually known only in a few patients. We reported the long term follow-up of a girl originary of Sicily (Italy) presenting such a mutation. The first 3 years of her life were previously reported (S.Guez et al Pediatr Nephrol 1998). In brief the child was pre-term born from related parents and she presented proteinuria (3-6 g/day) from birth. Renal biopsy was consistent with the diagnosis of CNS and molecular evaluation demonstrated a homozygous exon 27 R1160X nonsense mutation in the NPHS1 gene. In the first 2 years she was treated by human albumin without a regression of proteinuria that decreased up to 0.3-0.5 g/day with enalapril treatment (0.75 mg/kg/day); clearance of creatinine at 3 years of age ranged between 49 and 73 ml/min/1.73 mq. During the following 10 years (at the last control the girl was 13 year old) she had continued enalapril treatment (0.20 mg/kg/day). Creatinine clearance was 80 ml/min/1.73 mq/day, serum total protein 66 g/l; serum albumin 40 g/l and proteinuria ranged between 1.5-4.0 g/day. Both height and weight were at 50 th for age and pubertal stage was normal; blood pressure was 90/60 mmHg.

In conclusion, this is the first reported long-term follow-up in an Italian patient affected by Finnishtype CNS with the specific R1160X nonsense mutation in the NPHS1 gene: even if proteinuria persisted there was no worsening in GFR. Serum total protein, albumin and growth were normal confirming the milder phenotype in comparison with the typical Finnish forms. Long-term enalapril treatment may also have contributed to the prognosis in this specific form of congenital nephrosis. Atypical hemolytic uremic syndrome (aHUS) frequently results in end-stage renal failure and can be lethal in many cases. Recently, it has been recognized that many cases of aHUS are associated with a defective control of the complement activation cascade. More than sixty different mutations in complement factor H gene (CFH) have been reported so far. Guidelines for treatment modalities are yet to be established although plasma infusions and exchanges are often advocated. We describe a patient who presented at 7 months of age with aHUS (anemia, thrombopenia, acute renal failure requiring hemodialysis) associated with heterozygous combined de novo complement factor H mutations (S1191L and V1197A) on the same allele. Laboratory investigations showed normal levels of complement C4, C3 and Factor H. During the first episode, daily plasma exchanges (PE) using cryosupernatant (Cr) as replacement fluid resulted in a resolution of hemolysis and complete normalization of renal function. Two aHUS recurrences were successfully treated with daily PE and subsequently PE were weaned to twice weekly. One year after the first episode, PE were stopped and PI regimen (30 ml/kg twice weekly and weekly thereafter) was started. At the present time, the patient has been receiving weekly PI (30 ml/kg) for one year. Transitory falls in haptoglobin levels or platelet counts are observed periodically and successfully treated by intensification of PI (30 ml/kg) twice weekly for one or two weeks. Renal function remains normal.Although our observation demonstrates the effectiveness and good tolerance of large volumes of PI (30 ml/kg), long-term efficacy of such a therapy remains to be evaluated. Because of the possibility of secondary failure of plasma therapy, it is important to investigate alternative approaches such as combined liver-kidney transplantation. Common variable immunodeficiency (CVID) is characterized by reduced serum immunoglobulin levels and recurrent bacterial infections. There have been only 3 previous case reports of renal granulomas in CVID and only one of them was associated with immune complex glomerulonephritis. We present a case of renal granuloma and glomerulopathy in a patient with CVID. A 17-year-old girl, with a past history of uveitis, presented with cardiac tamponnade and bilateral pleural effusions. Investigations revealed nephrotic syndrome (serum albumin of 23 (normal 41-54) g/L and proteinuria >3g/L), microscopic hematuria and reduced serum IgG levels (4.49 g/L, normal 5.29-15.21 g/L). Lupus nephritis and serositis were first suspected and corticosteroids were initiated. No serum anti-nuclear or anti-DNA antibodies, nor complement activation were detected. A renal biopsy was performed and showed global glomerular endocapillary proliferation. Intratubular calcium deposits were present. In the interstitium, a noncaseating epithelioid granuloma was found. Immunofluorescence studies showed significant mesangio-parietal IgM deposits with few C3 and C1q. As IgM-immune complex glomerulonephritis has been reported in sarcoidosis, this diagnosis was highly suspected. Further investigation revealed normal lung parenchyma and mediastinum, normal serum angiotensinconverting enzyme, 1.25 OH 2 D 3 , calcemia and calciuria. The nephrotic syndrome gradually improved, but serum IgG levels remained persistently low (2.73 g/L). The diagnosis of CVID was confirmed and IV immunoglobulins were initiated. This is the first report of concomitant renal granuloma and IgM-immune complex (without IgG) glomerulonephritis in a CVID patient. In summary, CVID must be included in the differential diagnosis of renal granuloma and should be differentiated from sarcoidosis to ensure appropriate therapy.

O. Nwobi, C. Abitbol, J. Chandar, W. Seeherunvong, G. Zilleruelo

Background: Rituximab, an anti-CD 20 antibody, has been proposed as therapy for refractory systemic lupus erythematosus (SLE), although its use in children remains anecdotal. We present our initial longterm experience on the safety and efficacy of Rituximab for treatment of SLE in children.

Methods: 17 pediatric patients with SLE refractory to standard treatment protocols were treated with Rituximab for 2-4 doses (375 mg/m 2 ). All had proliferative nephritis and systemic manifestations of vasculitis. Clinical disease activity was scored using the SLE-Disease Activity Index (SLEDAI). Proteinuria is reported as the urine protein to creatinine ratio (Upr/cr). Patients have been followed an average of 2.3±I.2 years. Results: B cell depletion occurred within 1 month and remained suppressed for up to 3 months. Clinical course, renal function and proteinuria improved in the majority of patients as summarized below: Objective: to assess efficiency and safety of treating CRNS patients with SRL. Subjects: 5 patients, mean age 11.6 years old (6 yrs-18 yrs) (3 females) affected by CRNS. Inclusion Criteria: histological diagnosis of Focal and Segmental Glomerulosclerosis, glomerular filtration rate (GFR) above 60ml/min/1.73 m 2 , negative plasma pregnancy test, signed child and parents informed consent. Exclusion Criteria: secondary nephrotic syndrome, white blood cells (WBC) count below 4000/mm 3 , chronic hepatopathy, coagulopathy, tumoral or infection processes. Discontinuation Criteria: sustained decrease in GFR by more than 30% of the initial rate, decrease of the WBC count to less than 4000/mm 3 , occurrence of lymphoprolipherative and tumoral processes, severe infection, alterations in coagulation parameters, positive pregnancy test or inflammatory process or lack of changes in proteinuria or its increase after four-month treatment.

Methods: SRL dose and dosage: dose of 1 to 2 mg/m 2 /day (up to 5 mg/day) administered once a day. Expected dosage range: 5 to 10 ng/ml (HPLC-UV method). Treatment duration: 12 months. Results: 3 patients showed nephrotic syndrome remission; average SRL dose: 2 mg/m 2 /day; average SRL dosage: 5.75 ng/ml (range 5.3-6.3). Average proteinuria prior to treatment: 157 mg/m 2 /hour (range 80-263); average proteinuria after treatment: 3 mg/m 2 /hour (range 2.5-4); average time of remission: 2 months and 20 days, none of 5 patients showed adverse events that would have lead to the treatment discontinuation. If these data are representative of the universe of patients we are dealing with, the confidence interval (P=0.95) of the percentage of patients with not proteinuria after treatment is going to be between 45% and 75% if 40 patients are assessed.

Conclusions: SRL caused CRNS remission in patients who were refractory to traditional immunosuppressive treatments. Background: Retinoic acid-inducible gene-I (RIG-I) may play an important role on inflammatory and immune processes by regulating the expression of various genes, and has been reported to be expressed in various inflammatory diseases. We studied the expression of RIG-I in human lupus nephritis and evaluated the correlation between its expression and the histological activity of the renal disease in these cases. Methods: Expression of RIG-I in the glomeruli was assessed by indirect immunofluorescence method; frozen sections of ten kidney tissue specimens obtained from eight patients with lupus nephritis were stained with a monoclonal antibody for RIG-I. Kidney tissue specimens from eight patients with minimal-change (MC) disease were used as controls.

Results: Expression of RIG-I was detectable as granular immunofluorescence in a mesangial and capillary distribution in all the patients with lupus nephritis, but was absent or only trace-like in the patients with MC disease. The glomerular immunoreactivity for RIG-I was correlated with the histological activity and severity of the renal disease in the patients with lupus nephritis. Conclusions: RIG-I expression occurs at levels detectable by indirect immunofluorescence and may be potentially useful as a parameter reflecting the renal histological activity in cases of lupus nephritis.

Cyclophosphamide Pulse Therapy for Crescentic, Proliferative IgA Nephropathy in Children IgA nephropathy is one of the most common glomerular kidney diseases in Europe, up to 25% of affected adults need dialysis after 10 years. Therapy of crescentic, proliferative IgA nephropathy in children is not well examined. Between 01/2000 and 12/2006 seventeen children (main age 10 years (6-18), male/female=10/7) with biopsy-proven mesangioproliferative glomerulonephritis as manifestation of IgA nephropathy were enrolled. Nine patients (male/female=7/2) had severe clinical manifestations (renal failure, nephrotic proteinuria or cerebral vasculitis) with extracapillary glomerular proliferations (crescents). This children were treated by intravenous methylprednisolone pulses (400/200/200/100 mg/m 2 body surface area over 4 days) followed by monthly intravenous cyclophosphamide (CPH) pulses (6x500 mg/m 2 body surface area) with gradually tapered oral prednisolon (4-10 mg/m 2 body surface area/48 h over 6 months) and ACEinhibitor (enalapril 0.05-0.2 mg/kg/d). After 6 months of treatment a significant reduction of proteinuria (2.9±0.4 to 0.24±0.08 g/m 2 /d; P<0.0001) and improvement of kidney function (GFR 117±20.5 vs. 174±7 ml/min/1.73 m 2 , P<0.05) was observed. No notable adverse events were recorded. Six patients had a second renal biopsy after completing CPH-therapy; only 1 crescent was found in 245 examined glomeruli (Initial findings: 48 crescents in 231 glomeruli). After follow-up of 37 (8-75) months all children have unaltered renal function, further episodes of macrohematuria or gross proteinuria did not occur. Intravenous CPH pulse therapy seems to be an effective therapeutic option in paediatric patients suffering from crescentic IgA nephropathy.

Eye Involvement in Children with Primary FSGS Distinct eye abnormalities have been described in children with nephrotic syndrome, particularly in diffuse mesangial sclerosis (Pierson syndrome). The aim of the study is to investigate whether there are any associated ocular anomalies in childhood primary focal segmental glomerulosclerosis (FSGS). Demographic characteristics, age at onset, drug therapy and duration of the disease were defined in 30 patients (14 girls,16 boys, mean age 10.1±3.9 years) with biopsy proven FSGS. Standard steroid therapy was prescribed to the patients. A detailed ophtalmological examination was performed in all patients. The median age at diagnosis was 6 years (1-16 years). Mean followup time was 36 months (4-116 months). Eleven patients (36.6%) reached to chronic renal failure during follow-up period. Overall, 15 patients (50%) showed various eye abnormalities. Nuclear opacity was found inone child and posterior subcapsular opacities probably due to corticosteroid therapy were present in two cases. Two patients had myopic astigmatism and two had exotrophia. Importantly, 4 patients had anisometropic ambliyopia, 3 had Mittendorf spots and 1 had pigmentary changes in macula, which had never been described in the literature. Mutational analysis for nephrin, podosin, WT1 and LAMB2 genes are still going on. We don't know whether particular mutations are related to particular eye findings like Pierson syndrome, yet. However our findings emphasize that ophtalmological evaluation should be performed in all patients with primary FSGS at the time of diagnosis.

Regardless of the underlying disease, the proteinuric condition demonstrates ultrastructural changes in podocytes with retraction and effacement of the highly specialized interdigitating foot processes.

To investigate whether high glucose and advanced glycosylation endproduct (AGE) induce podocyte phenotypical changes, including quantitative and distributional changes of ZO-1 protein, we cultured rat glomerular epithelial cells (GEpC) under 1) normal glucose (5mM,=control) or 2) high glucose (30 mM) or 3) AGE-added or 4) high glucose plus AGE-added conditions. High glucose plus AGE-added condition could increase the permeability of monolayered GEpCs and induce ultrastructural separation between confluent GEpCs. ZO-1 moved from peripheral cytoplasm to inner actin filaments complexes by both AGE-added and/or high glucose condition in cutured GEpC by confocal imaging. High glucose plus AGE-added condition also decreased ZO-1 protein amount and its mRNA expression to statistically significant level compared to normal glucose or osmotic control conditions. We could also confirm the activation of PKB/Akt signaling pathway in GEpC by AGE, high glucose and insulin in PI3K-dependent manner. In addition, an inhibition of PI3 kinase by LY294002 was able to prevent quantitative and distributional changes of ZO-1 protein induced by high glucose and AGE. These findings suggest that both high glucose-and AGE-added condition induce the cytoplasmic translocation and suppresses the production of ZO-1 at transcriptional level and these changes may be mediated by PI3K/Akt signaling. This pathway could explain the role of ZO-1 in the phenotypic changes of podocytes in diabetic conditions. Henoch-Schönlein purpura (HSP) is common in the pediatric population, while Wegener's granulomatosis (WG) is rare. Although both diseases are classified into the vasculitis syndrome, their clinical symptoms, the treatment and the prognosis are considerably different. The classic clinical triad of WG consists of upper and lower airway disease, renal involvement and small vessel vasculitis. We present a rare childhood case in whom HSP-like symptoms were developed prior to WG symptoms. A 13-year-old girl developed ankle joint pain and swelling and purpura on bilateral legs and hands in the absence of abdominal pain. She was diagnosed as HSP and treated with oral prednisolone (PSL) therapy. Although high dose PSL temporarily rescued these symptoms, purpura and joint swelling and pain reappeared in parallel with a reduction of PSL dose. At this moment, because microscopic hematuria, mild proteinuria and hoarseness were also noticed for the first time, serum proteinase-3 antineutrophil cytoplasmic antibody (PR-3ANCA) was evaluated and detected to be high. Moreover renal pathology showed necrotizing pauci-immune glomerulonephritis, leading to the final diagnosis as WG. After methylprednisolone pulse therapy followed by oral PSL combined with cyclophosphamide, her clinical symptoms with WG were resolved together with the reduction of serum PR-3ANCA titer. Taken together we emphasize that PR-3ANCA should be evaluated even in the patients who only develop HSP symptoms. Background: Short-term efficacy of steroid therapy for pediatric patients with IgA nephropathy (IgAN) has been reported. However, there are a number of cases in whom their IgAN recurs after stopping the steroid therapy. Recent Japanese study indicated that tonsillectomy had a significant impact on renal outcome. Also, another Japanese study showed mizoribine was effective for IgAN in children. In this study, we examined the effects of a treatment regimen consisting of tonsillectomy and steroid pulse therapy followed by mizoribine (Tx) for chronic relapsing IgAN in children.

Method: Ten cases who showed chronic relapsing IgAN were included as the subjects (mean age at onset: 12.0 yrs, mean age at initiation of Tx: 19.4 yrs). They were divided into two group, a normal renal function group (Group A, N=6) and an impaired renal function group (Group B, N=4). The changes in hematuria, proteinuria, renal function, and adverse events were prospectively examined for more than 12 months. Result: A negative of hematuria was observed in 50% of Group A and 75% of Group B. A negative of proteinuria was seen in 33% of Group A. In addition, in Group B, deterioration of renal function was not observed during the observation periods. There were no serious adverse events associated with this treatment regimen. Conclusion: A treatment regimen consisting of tonsillectomy and steroid pulse therapy followed by mizoribine treatment seems to be effective to control of acute inflammation coexisting with chronic glomerular lesions, and can be a valuable addition to therapeutic options for treating patients with chronic relapsing IgAN in children. Objective of Study: To present a case of silent stenosing ureteritis in a boy with Henoch-Schönlein purpura (HSP). Case report: A 4-year-old boy was admitted with a typical HSP. Urine findings were normal on admission. A gastrointestinal bleeding on the 4 th day of illness suggested corticosteroid treatment. The ultrasound on the 4 th and 7 th day revealed a normal urinary tract. On the 10 th day he developed non-painful macroscopic haematuria, followed by microscopic haematuria and proteinuria, which reached the nephrotic range on the 11 th day. Thus, the boy was treated with methylprednisolone pulses and cyclophosphamide for 8 weeks. Renal biopsy was not performed because of his parent's refusal. Microscopic haematuria and proteinuria gradually subsided, with complete disappearance at the 5 th month. During this time he was asymptomatic, with no episodes of macroscopic haematuria or colicky flank pain. At the 8 th month of illness a new ultrasound revealed a major left hydronephrosis. Computer tomographic urography showed a complete ureteropelvic junction obstruction. The 99mTc-DMSA scan revealed a 5% relative function ipsilaterally. A left pyelostomy was performed. During the next four months after draining, the urine volume of the affected kidney was 0.2-0.3 ml/kgr/hour, the creatinine clearance 2-3 ml/min/1.73 m 2 and the 99mTc-DMSA scan showed a 4% relative function. Based on the above findings a nephrectomy was decided.

Conclusions: Although rare, stenosing ureteritis should be considered in HSP. The typical clinical presentation with haematuria in association with colicky flank pain may not always occur, as in the present case, or may be confused with the symptoms of HSP itself. Thus, the repetition of an ultrasound during the process of the disease may be necessary, in order for this complication to be diagnosed and treated early, preventing serious renal outcome. Mitochondrial diseases are either due to sporadic or inherited mutations mainly in mitochondrial DNA located genes. With regard to renal manifestations, tubular dysfunctions are common; however, the existence of solitary glomerulopathy has recently become apparent. In such case, the pathomechansim of the glomerular proteinuria is still obscure. Wepresent a 12 year-old girl who was found to have asymptomatic proteinuria (UP/Cr1.0) in the absence of hematuria, azotemia, tubular dysfunctions, lacking any neurological manifestations. Her family history showed maternal inheritance with mild proteinuria of grandmother and renal insufficiency of young uncle. Light microscopy revealed 7 glomeruli of normal appearance and 3 of global sclerosis. Electron microscopy showed swollen mitochondria in podocyte of normal appearance glomerulus. Pointmutation rate of mitochondrial DNA, A3243G, was detected as less than 1% in grandmother, 6% in mother and 39% in the patient examined byperipheral blood cells. The proteinuria completely disappeared 3 months after treatment with combined therapy of ARB and ACEI. To determine the responsible molecule for the pathomechanism of proteinria, immunostaining followed by conforcal microscopy with slit diaphragm associated molecules (SDM) (nephrin, podocin), GBM associated molecules (type IV collagen alpha chains, laminin isoforms, perlecan) and podocalyxin was studied and compared to the controls. Interestingly distinct decrease of expression with SDM was observed even in normal appearance glomerulus of the patient. Taken together, A3243G mutation itself may lead to depletion of ATP and/or increase of free radicals in podocyte, which predominantly affect the biogenesis of SDM, result in pathological glomerular proteinuria. The mechanism of antiproteinuric effect of ARB/ACEI therapy should be evaluated by serial biopsy specimen.

Objectives: To report the effectiveness of pulse cyclophosphamide induction therapy in children with diffuse proliferative lupus nephritis. To identify predictors for unresponsiveness to the treatment.

Methods: Thai children under 15 years of age with biopsy-proven diffuse proliferative lupus nephritis who were admitted to Chiang Mai Universityhospital between 2001and 2006 were retrospectively studied. Responsiveness to treatment, defined as urinary protein to creatinine ratio of less than 0.3, was assessed at the end of induction period. The clinical characteristics and laboratory data including gender, age at diagnosis of SLE, duration of disease before treatment, hypertension, clinical nephrotic syndrome, amount of proteinuria, serum creatinine, creatinine clearance, serum C 3 level and presence of crescentic formation in renal biopsy were compared between the two groups who responded and did not respond to the treatment.

Results: A total of 27 patients (89% female) with the mean age at diagnosis of SLE of 10.3±2.6 year were studied. Nineteen patients (70%) achieved remission at the end of induction therapy. There were no significant differences in all parameters studied between responsive and nonresponsive groups. Despite the indifference in the amount of proteinuria, the proportion of patients with nephrotic-range proteinuria was higher in unresponsive group. Conclusions: Pulsecyclophosphamide is an effective regimen for induction therapy in children with diffuse proliferative glomerulonephritis. Although no definite predictor was detected in this study, higher proportion of patients with nephrotic-range proteinuria in the unresponsive group wasnoted.

Born Small for Gestational Age, but not Early Postnatal Weight Gain Aggravates the Course of Idiopathic Nephrotic Syndrome in Children Clinical and animal studies have shown a higher risk of an aggravated course of renal disease in childhood after birth small for gestational age (SGA). Fast catch-up growth after SGA seems to support the development of later disease. In a retrospective analysis of 62 cases with idiopathic nephrotic syndrome treated between 1994 and 2004 in a university centrefor paediatric nephrology we identified 6 children as SGA and 56 asappropriate for gestational age (AGA). We related the course of disease to birth weight and catch-up growth. Median age of manifestation in SGA was 6.4 (1.9-15.2) years vs. 3.7 (1.2-15.33 ) years in AGA children. In all SGA children renal biopsy was performed, while only 55% of the AGA children underwent renal biopsy showing nodifference in renal histology. In the SGA group, 66% patients developed steroid resistance (vs. 21% AGA, p<0.05). The number of relapses was not different. 83% SGA children needed antihypertensive treatment inthe course of the disease compared to 39% of AGA children. Catch-up weight gain between birth and 24 months of age did not influence the course of disease. In conclusion we could find evidence for an aggravated course of idiopathic nephrotic syndrome in former SGA children, but weight gainduring the first two years of life did not influence the course of disease. The mechanisms of perinatal programming in later renal disease need further investigation.

Wilson's disease(WD) is a disorder of copper metabolism that affects numerous organsystems including kidneys. Besides renal tubular dysfunction as a result of excessive storage of copper, renal manifestations due to therapeutic complications can also develope specially with D-penicillamin. In this study we investigated the frequency and spectrum of renal manifestations during D-penicillamin therapy in WD. Of 62 patients receiving D-penicillamin for WD, 4 patients(6.4%) (3 boys, 1 girl) developed findings of glomerulopathy within 1 month to 1 year after initiation of therapy and all were histologically diagnosed to have membranoproliferative glomerulonephritis (MPGN). The patients were between 6-11 years old, and they had normal urinalysis and renal function tests in their first presentations. Two siblings developed hematuria and proteinuria below nephrotic range while the other two developed nephrotic syndrome. One of these latter patientsalso had acute renal failure needing temporary peritoneal dialysis. Three patients had low complement (C) 3 levels, 2 had antinuclearantibody (ANA) positivity, two had c-antineutrophil cytoplasmic antibody (ANCA) and one p-ANCA positivity. D-penicillamin therapy replaced by zinc sulphate in all patients. All renal findings improvedin patients within 3-6 months with normal renal functions and complement levels, and negative ANA, p and c-ANCA tests. After 2 years all were clinically in remission of MPGN confirming the role of D-penicillamin in development of renal disease. Objectives of the study: The use of tacrolimus in steroid-resistant (SR) focal segmental glomerulosclerosis (FSGS) has been reported in single and small series. The aim of this report is to exhibit experienceon the management of children with SR FSGS in whom tacrolimus had been started on due to the therapy resistance. Methods: FK506 combined low-dose oral steroid was started on three male patients (3, 8, 14-yearold) with SR FSGS who had been following for three years. All of them had failed various cyclosporin A, cyclophosphamide and steroid regimens prior to treatment with FK 506. The application was 0.1 mg/kg/day in two divided doses over 12 h adjusted to a trough blood level between 5 and 10 ng/ml for 12 months. Other therapies included angiotensin-converting enzyme inhibitors, vitamin D and calcium analogues, and lipid-lowering agents.

Results: A reduction in proteinuria to normal levels was noted between 2-4 weeks following the initiation. The remission was achieved overall during the treatment. The relapse was recorded following cessation of tacrolimus in 2-4 weeks. The drug was generally well tolerated with no sideeffects and adverse reactions. The ratio of infectious events did not differ from the former regimens. Conclusion: Tacrolimus may be effective in controlling the proteinuria of patients with SRFSGS during the therapy. There is a trend of relapse following cessation of treatment. The duration for drug uptake is a topic of debate. Further study in larger population is warranted. Introduction: Histological features of focal segmental glomerulosclerosis are found in 75% of pediatric patients with steroid resistant nephrotic syndrome. Upto 50% (between 13-78%) children with FSGS progress to ESRD. Objective: To study the clinical course of childhood FSGS and determine the possible predictive factors of chronic kidney disease. Method: Case records of children who had biopsy proven FSGS and had presented to the Sindh Institute of Urology and Transplantation between 1995-2005, were retrieved. Clinical and laboratory parameters at baseline, response to steroids and cyclosporine, development of CRF (as defined by a GFR of <60 ml/min/1.73 m 2 ), and histopathological details were analysed.

Result: A cohort of 59 children with a mean age of 8.5±6.5 years and a M: F ratio of 3: 1 was identified. After a mean follow-up time of 5 years, 21/59 (35.5%) developed CRF. On univariate analysis, male sex (90% vs 65%, p-0.04), >6 years age at onset (62% vs. 32%, p-0.02), hypertension (57% vs. 26%, p-0.05) and microhematuria at presentation (62% vs. 25%, p-0.007) were significantly associated with risk of developing CRF. Steroid resistant course (90% vs. 53%, p=0.003) was more prevalent in those who developed CRF. The CRF group was also more likely to have an elevated creatinine at baseline (47.6% vs. 5%, p<0.05). Moderate tubular atrophy and a high percentage of segmentally and globally sclerosed glomeruli were found in those who developed CRF. Patients progressing to CRF were more likely to have a partial response to Cyclosporine (86% vs. 33%, p=0.02) Conclusion: Factors such as age, microhematuria, hypertension, elevated baseline creatinine, steroid resistance, tubular atrophy, percent global sclerosis and partial response to cyclosporine are likely predictive of progression to chronic kidney disease in children with FSGS presenting to our Center. Chronic glomerular nephropathies in children are marked by an often unfavourable evolution, so that the establishing of a prognosis at the time of the diagnosis is both a professional and a moral duty for the pediatric nephrologists.

Purpose: the estimation of the current practice renal survival prognosis in children with chronic glomerular nephropathies, by using clinical and laboratory elements in different histological forms of primitive chronic glomerulonephritis (CGN), with a minimum period of observation of one year. We analyzed parameters that may intervene in the duration of renal survival: type of CGN, age at the debut of the illness, histological scores of activity and chronicity, the presence of tubular atrophylesions and that of interstitial fibrosis, renal failure (RF) installment time, in cases with normal renal function at the beginning, the time until the initiation of dialysis in cases with ESRF, respectively. The statistic analysis of data has been carried outwith Epi soft (Fishcer test).

The results have been as follows: unfavourable evolution has been taken into consideration in the cases which have presented fixed nitric retention or which required the initiation of dialysis. The initiation of dialysis was necessary in 19 cases (76%), out of which 11 (44%) having associated between 4 and 6 of the considered risk factors. If the histological type (SFGS, DGS, MPGN) is added to the obtained score, the accuracy of the estimation increases to 89%.

In conclusion: the usage of prognosis scores composed of current elements of diagnosis that have proven to have statistical significance, as far as the renal survival prognosis is concerned, may allow the invoking of a medium-term prognosis in the evolution of children with CGN. Introduction: The SRNS can lead to a progressive deterioration of the renal function and therefore needs an aggressive therapy. One of the alternatives of treatment is the association described by Mendoza et al which consists of prolonged use of Methylprednisolone with Cyclophosphamide (CP), which has a remission rate of 66%. The objective of this study is to evaluate retrospectively the clinical evolution of 15 children with SRNS treated with Mendoza's protocol. Method: Between 1993 and 2005, 15 children, 8 male and 7 female, with SRNS were subjected to a renal biopsy and later treated with Mendoza's protocol. CP was used in children that had not responded to pulses of Methylprednisolone and presented a relapse. All of the patients received supplemental calcium. The clinical evaluation included stature, weight, ophthalmic fundus examination, proteinuria in urine recollection of 24 hours and/or protein to creatinine ratio and blood chemistry. Results: Eleven patients (73%) had FSGS. Nine (60%) presented complete remission, two (13%) had partial remission, four (26%) did not respond to treatment, 3 of which evolved to terminal kidney disease. Nine patients received CP. Of the complications secondary to treatment with steroids, 80% had a linear growth suppression and an increase in their BMI and 1 patient presented cataracts with visual impairment. Conclusion: The prolonged treatment with boluses of Methylprednisolone and Cyclophosphamide is a good alternative in patients with SRNS. The prolonged use of high doses of steroids can cause linear growth suppression and other adverse reactions, so it is advisable torealize a genetic study in all of the patients with SRNS to be able to exclude the patients that have a genetic mutation and so avoid unnecessary treatment. Objectives: To study the clinicopathological profile and outcome of lupus nephritis (LN) in Indian children.

Methods: Clinical and histopathological features and outcome of children with LN was retrospectively reviewed. Patients were included if they fulfilled the ACR criteria for the diagnosis of SLE and had either of persistent proteinuria, active urinary sediments or renal dysfunction. Outcome was analyzed at 3 years and at last follow-up. Results: Ofthe 53 children studied, 13 were boys. The mean age (SD) at diagnosis was 9.8±2.3 (median 9.8, range 5-14.4) yr; 23 children were youngerthan 10 years of age. The mean age at presentation and renal biopsy was 10.8±2.2 (median 10.4, range 6.5-15) years. The mean duration of follow-up was 3.1±2.9 (median 2.5, range 0.2-10.3 years) years. 41.2% patients were followed for more than 3 years. Commonest clinical manifestations were fever (77%), hypertension (58%) and malar rash (56%). 35 and 28% of patients presented with nephrotic and nephritic syndrome respectively before the diagnosis of SLE. The commonest pathology was class IV nephritis (41%) followed by class II (17%). Hypertension, hematuria, nephrotic syndrome and decreased eGFR were significantly associated with Class IV LN. At last follow-up 31.5, 15.7 and 0% patients were in CKD stage II, III, and IV respectively. The patient survival rate at 3 year and at last follow-up was 100 and 94% respectively, while no patient developed ESRD at 3 years. Infections were seen in 30% cases that resulted indeath in 2 patients; 1 died of hepatic encephalopathy. Conclusion: SLE nephritis has a varied presentation and high morbidity. A significant proportion of patients developed infections during the course of disease. Clinical, pathological features and outcome in our study do not differ markedly from those in most pediatric series. Background: Atypical HUS has a frequently relapsing course and a poor renal prognosis. Low C3 plasma concentration suggests alternate complement pathway regulatory abnormalities: factor H (FH), factor I (FI) and membrane cofactor protein (MCP). Case report: We report an 11 year old girl with atypical HUS due to acquired FH deficiency caused by anti-FH antibodies (Abs). HUS was diagnosed on the basis of acute renal failure, microangiopathic hemolyticanemia and thrombocytopenia. Past history: recurrent fever with culturenegative pharyngitis (suspected PFAPA syndrome). Decreased C3 (64 mg%, normal>80) with normal C4. ADAMTS 13 activity was depressed, no cleaving protease Abs. Hemodialys (HD) and plasma exchange (Pex) were started 12 days later. Severe urticaria and angoiedema during Pex was treated with methylprednisolone and chlorpheniramine. Hematological and renal improvement were observed after the 3 rd Pex session. 4 relapses occurred in 3 months: 1 -controlled by Pex; 2 -(with suspected PFAPA) with single dose corticosteroids, 3 -with prednisone therapy, 4terminated with single dose IVIG 200 mg/kg. Elevated anti FH Ab titer-1471 AU with decreased FH functional activity were found in pre-Pex plasma. FH, FI, factor B and C3 antigenic levelsnormal. Hematological remission and renal function improvement without HUS relapse ensued while tapering corticosteroids. Two years after presentation, onprednisone 5 mg/day anti FH titer dropped significantly with restoration of functional FH activity, GFR ~75ml/min/1.73 m 2 .

Conclusions: In cases of atypical HUS, active search for anti FH Ab iscrucial for implementing specific and effective therapy: plasma exchange, IV IG and steroids for improving course and longterm prognosis.

Research Centre for Child Health RAMS, Department of Pediatric Nephrology, Moscow, Russian Federation 25 children aged 1,5-16 years with idiopathic biopsy-proven steroid-resistant focal and segmentary glomerulosclerosis (FSGS) were treated with Cyclosporine A (CsA) 3,2-7,6 mg/kg as initial dosage, oral prednisolone 1,5 mg/kg every other day tapered to the 12-th month and methylprednisolone pulses (MP) 20-30 mg/kg every other day for the first 2-4 weeks in 17 of patients. Serum creatinine level was controlled once a month. After 6 months of CsA treatment complete or partial remission of proteinuria was in 15 (60%) of children, no effect in 10 (40%). Serum creatinine level increased in 14% on an average in the group remission of proteinuria. In the group of non responded patients the creatinine elevation was significant same -15%. After 1 year of CsA treatment complete or partial remission observed in 18 (72%), no effect in 7 (28%). Elevation of serum creatinine level in children with remission was 15,5% (without significant difference compared to 6 month's CsAtreatment). Increasing of the creatinine level more than 30% in two patients leaded to double tapering CsA dose resulted in normalization of serum creatinine level. In the group of CsA non responders the significant increasing of serum creatinine level (35%) was revealed (compared to 6 month's CsA treatment). In 3 cases the elevation ofcreatinine level was more than 50% and these patients turned into ESRD eventually. In all of non-responders CsA was discontinued. We concluded that serum creatinine level in CsA respondrers was stable without significant elevation during the 1 year of treatment. CsA therapy for 1 year without any effect influenced on renal function decreasing.

Clinical Objective: To describe the clinical course and outcome of pediatric patients with CGD treated with IV MPT (30 mg/kg x 3 doses monthly for 12 months, then 1 dose monthly for the next 6 months) Methods: Patients' medical records were reviewed. Pre, post-treatment and follow-up 24 hr urineprotein, creatinine and GFR were compared using paired T-test; and proteinuria, hematuria and blood pressure using McNemar's chi square. Outcome measures were analyzed usingmean ± SD and frequency distribution. Results: 30 patients were included, 13 male, 17 female. Mean age at disease onset is 7.972±4.298 years. Mean duration of follow-up is 23.733±18.714 months. 70% achieved complete remission after a mean of 1.8 cycles, 17% partialremission after a mean of 2.8 cycles and 13% were treatment failures. Mean relapse rate is 0.700±1.208 on treatment and 0.733±1.596 at follow-up. Renal survival rate is 93%. 24 hour urine protein and the proportion of patients with proteinuria, hematuria and hypertension significantly decreasedafter treatment and remained stable at follow-up. Serum Cr/GFR were also stable pre, posttreatment and at follow-up. No serious side effects were noted. Conclusion: This protocol induced a high and early remission rate (70% after 1.8 cycles)among the patients. Majority demonstrated stable renal function and blood pressure over time. Relapse rates were low and treatment is generally safe. Recommendation: The protocol can be offered to oral-steroid or alkylating agent-resistant patients with satisfactory remission rates. Objectives of study: Nestin, an intermediate filament protein which has a role in regulating cellular cytoskeletal structure, is restrictedly expressed in the podocytes of human kidneys. In the present study nestin expression was investigated in biopsy specimens of children with focal segmental glomerulosclerosis (FSGS). Methods: 36 kidney biopsy specimens taken from children with diagnosis FSGS were investigated. Diagnosis was performed on light microscopy, immunofluorescence microscopy, taking into account clinical data. For immunomorphology monoclonal anti-nestin antibody from mouse (SC-23927, clone 2C1.3A11, Santa Cruz Biotechnology) diluted 1: 100, was applied on cryostat or paraffin sections using Labeled StreptAvidineBiotin (LSAB+ Dako) method. Visualization was performed by Dako AEC substrate. 10 kidney biopsies of patients without nephrotic syndrome, mainly with mesangioproliferative GN were used for control staining.

Results: The mean age at the time of biopsy was 10.2±4.9 years, and all patients had nephrotic syndrome. Half of them revealed some focal tubulointerstitial changes: tubular atrophy, slight interstitial fibrosis and lympho-monocytic infiltration. In two cases mutation of WT1 gene and in one case mutation of NPHS2 gene was detected. Four cases had familial character of FSGS. Nestin expression was variably present in different cases of FSGS. Decreased expression was detected in glomeruli with segmental mesangial sclerosis and capsular adhesions. Conclusion: FSGS revealed heterogenity concerning nestin expression. Nestin expression was diminished in affected glomeruli. Background: Renal effects of altered Ob/Ob-R pathway may contribute to obesity, and diabetesassociated proteinuria. In the kidney Ob/Ob-R stimulates collagen type I and IV synthesis and upregulates TGFβ1 and TGFβ2 receptors. Objective: To determine Ob/Ob-R and its downstream (JAK/STAT/SOCS) pathway expression in nephrotic syndrome (NS) and FSGS. Design/Methods: Microarray analysis of kidneys of 2-week (2w) and 4-month (4m) old transgenic mice (TG) and controls (CTR) was performed, and confirmed by quantitative PCR. Kidney sections were analyzed by immunohistochemistry (IHC) and western blot analysis (WB). Urinary Ob/Ob-R of children with NS classified as steroid sensitive (SSNS) or steroid resistant (SRNS), were measured by ELISA.

Results: Ob, Ob-R, and JAK1,2,3 mRNA expressions were not statistically different at 2w and 4m between CTR and TG. STAT3 and SOCS mRNA were increased 2.04-fold (SEM ±0.52), and 17.38fold (SEM±8.6) at 4m in TG, p=0.04 and p=0.01 respectively. IHC and WB (p=0.65) of kidney sections showed no significant difference between the 2 groups. We examined 12 CTR, 10 SSNS, and 11 SRNS patients with comparable BMI, age, race and gender. Urinary protein to creatinine ratio in SSNS and SRNS was 0.18 (SEM±0.06) and 3.12(SEM±1.03) respectively, p=0.03. Urinary Ob (p=0.1), Ob-R (p=0.09), and TGFβ1 (p=0.12) were not statistically significantly different between the 3 groups.

Conclusions: Ob/Ob-R was not upregulated in TG at the onset of proteinuria and FSGS. However, advanced FSGS (4m TG) showed significant activation of SOCS3, an Ob/Ob-R negative regulatory pathway. Pediatric patients with early SRNS had no significant increase in urine Ob/Ob-R. This data suggests the role for Ob/Ob-R regulatory pathways in the development of advanced FSGS. Primary FSGS presents clinically with steroid-resistant (SRNS) or steroid-dependent (SDNS) nephrotic syndrome or proteinuria. The data shows, that 43% patients with FSGS progress to ESRD in 15 years follow-up.

Objectives: The aim of the study was to analyze the long-term outcome of patients with primary FSGS diagnosed in kidney biopsy. Material: The study group consisted of 113 children (54 males, 58 females) followed from 1982. All patients were treated with immunosupression and renoprotection. The clinical data were analyzed after follow-up lasting for mean 10±6,1 years (0,5-25 years) . 85 children presented with nephrotic syndrome (66 SRNS and 17 SDNS) and 28 with proteinuria. The age ranged from 0,5-16 years mean 5,9±4,5 at the time of diagnosis. More then 1 kidney biopsy was performed in 55 children -in 29 progression from MCD (N=18) and MES (N=11) to FSGS were observed. Results: The clinical remission was observed in 73/113 patients (64%) and was not correlated with initial proteinuria (mean 11,3±9). In 20/113 patients CRF was observed, 15 of them progressed to ESRD (12 were successfully transplanted). Among patients, who had FSGS as their initial glomerular lesion (N=84), the percentage of glomerular sclerosis was significantly higher in a group in which remission was not obtained after long-term follow-up (31,7 vs. 17%, p<0,001). In 9 out of 49 patients with follow-up over 10 years progression to ESRD was observed (18,4%), 10/49 were transmitted to adult centers with persistent proteinuria.

Conclusions: Immunosuppression and renoprotection in patients with FSGS can prevent the progression of CRF. Extensive glomerular sclerosis is a predictor of unfavourable outcome. Further clinical and genetical studies are needed to establish the effective therapy modalities.

Mycophenolate and who had previously undergone a renal biopsy, recieved 600 mg twice daily (maximum 1 gram twice daily) during six months. Prednisone was concurrently prescribed at at dosage of 1 mg/kg/every other day, during 8 weeeks and 0.5 mg/kg/every other day during the subsequent 8 weeeks. Results are expressed as mean±SD.

Results: Seven chidren, 5 boys and two girls were enrolled. Oncet of their NS was at age 6.2±4, 16 yr (range 2-13 yr) and MMF was initiated at 9.4±4.4 yr (4.5-15.5 yr) . Six were SR and one SD. Two patients had previously recieved cyclosporine, two patients cyclophosphamide and one chlorambucil. Renal histology displayed: focal segmental glomerulosclerosis (n=3), minimal change (n=2), mesangial proliferation (n=1) and membranous glomerulonephritis (n=1). At the end of the follow-up: three patients were in partial remission, two were in complete remission and two had no response to MMF. Initial and final serum creatinine concentration 0.53±0.08 vs 0.57±0.09 mg/dl), estimated GFR (124.2 vs. 111±37 ml/min/1.73 m 2 ) and serum albumin ( Idiopathic nephrotic syndrome is the most frequent glomerular disease in childhood. Most patients are steroid responsive but half of them relapse and often become steroid-dependent. They are exposed to long term steroid complications on the one hand and relapses due to insufficient disease control on the other hand. Our aim is to determine predictive risk factors for high degree steroid dependence.

In France, steroid-resistance is defined as persistent proteinuria after one month of daily oral prednisone (60 mg/m 2 ) and 3 pulses of methylprednisolone (MPN) (1 g/1.73 m 2 ). We included 27 steroid responsive children with disease onset between 2000 and 2006.

The mean age at diagnosis was 4.6 years (range 1.5-16). All patients initially received prednisone 60 mg/m 2 per day. The following parameters were analysed: age at onset, gender, days to remission with initial steroid therapy, MPN pulses, numbers of relapses, steroid dependency, immunosuppressive drugs. Twenty of the 27 patients were steroid-dependent; among the 20 steroid dependent patients, 11 received MPN pulses. 90% of those patients (10/11) were treated by cyclosporine during follow-up.

On the other hand, only 10% (1/9) of the patients who did not receive MPN required cyclosporinebased therapy during follow-up (Chi-square test, p=0.0018).

Interestingly, there was no correlation between treatment days until remission during the initial prednisone course and the risk for later steroid dependence. Conclusion: The need for MPN pulses, but not the time interval until remission helps to predict steroid dependence. Patients, necessitating MPN pulses to obtain remission are at risk to require cyclosporine for disease control. By identifying these children, we could eventually 1/ avoid multiple relapses by earlier use of adequate immunosuppression and 2/ avoid side effects related to long term high dose steroid therapy. Membranous nephropathy (MN) with antitubular basement membrane antibodies is a rare condition. Relapse of tubular dysfunction in renal transplant recipients has been published in one case, but relapse of MN in the renal graft has not yet been reported. A 3-year old boy presented first with steroid resistant nephrotic syndrome associated to tubular dysfunction. Renal biopsy revealed MN associated to interstitial fibrosis and granular deposits of IgA, IgG, and C3 along the tubular basement membrane. Indirect immunofluorescence (IF) revealed circulating anti-tubular basement membrane antibodies. He received a renal allograft at the age of 6 years. An acute rejection episode on day 21 required three steroid pulses and OKT-3. Renal biopsy revealed the presence of interstitial and vascular rejection (BANFF III) and relapse of tubular basement membrane deposits. Renal function normalized within 10 days and remained stable (GFR estimated by Schwarz formula=103 ml/min per 1.73). Proteinuria remained negative and urinalysis normal over 5 years under the immunosuppressive regimen including FK, AZT, and prednisone. At the age of 11 years, proteinuria increased progressively over 6 weeks reaching 2.8 g/day, whereas serum creatinine remained stable. Renal biopsy revealed the presence of granular deposits along the glomerular basement membrane suggesting a late relapse of MN in the transplant. Rituximab therapy (day 0, 15, 30, and 60) followed by switch from azathioprine (AZA) to MMF resulted in a complete biological remission with negative proteinuria. Indirect IF revealed progressive decrease of antitubular basement AB level during Rituximab treatment and a negative signal was obtained 3 months after the switch from AZA to MMF. This is the first report of glomerular relapse of MN with anti tubular basement antibodies in a renal transplant recipient. Nephrotic children are at risk for severe pneumococcal infections. The best moment for antipneumococcal vaccination is controversially discussed. We investigated the serologic response after Pneumo23 vaccination in 25 children (10 girls) with nephrotic proteinuria and hypoalbuminemia, immediately after initialisation of prednisone therapy at 60 mg/m 2 (group 1) and in 16 children after tapering down of prednisone to <0.5 mg/kg EOD (group 2). There was no difference in both groups concerning antibody (AB) response, relapse frequency, or number of steroid dependent forms. In group 1, Pneumo23 AB levels at presentation (M0) were 1.20±0.22 (mean±SE) . At M1 antibody levels increased 9-fold to 9.28±1.35 (p<0.0001). Serum levels at M3 were 7.58±1.67. One year after vaccination AB levels (4.4±1.78) decreased compared to M1 (p<0.01), but remained increased compared to M0 (p<0.01). There was no increased delay until remission in both groups compared to a retrospective control group. Severe hypoalbuminemia (<10 g/L) at the time of vaccination was not related to a lower serological response on M1. During relapses, antibody levels decreased significantly compared to levels before relapse (p<0.01), but increased again once remission was obtained. Even during relapses, AB levels remained higher (>3-fold) than pre-vaccination levels.

Conclusion: Nephrotic children on high dose glucocorticoid therapy respond to anti-pneumococcal vaccination and their AB levels remain elevated during relapses. Vaccination at disease onset may be beneficial as those patients with relapses during the tapering down of steroids already have increased anti Pneumo23 AB at the time of relapse.

Crescentic Glomerulonephritis with Isolated C3 Deposits Associated to Complement Abnormalities: a New Entity? Introduction: Several progressive renal diseases present proteinuria, as a result of glomerular and tubulointerstitial injuries. Thus, some studies prove that proteinuria is an important predict factor for progression of renal failure. Angiotensin converting enzyme inhibitors (ACEi) are efficient in reducing proteinuria and preserve renal function in patients with diabetic or non-diabetic nephropathy. The purpose of this study was to evaluate the efficacy and security of ACEi in children.

Material and methods: The ACEi (enalapril) was used in normotensive and hypertensive patients with chronic renal disease, with microalbuminuria/proteinuria. Results: We studied 28 patients (13 girls), for at least 6 months, mean age was 10.4±3.5 years (1 month to 17 years). 5/28 patients had glomerulopathy, 13/28 chronic pyelonephritis, 4/28 systemic disease, 2/28 renal hypoplasia/ dysplasia, 3/28 cystic renal disease and 1/28 arterial hypertension. The mean dose of enalapril was 0,25mg/kg/d (0, 04 to 0, 38) and it was used during 36,6 months (mean). We observed a normalization of proteinuria/microalbuminuria in 53, 5% of cases. In seven patients, the drug was discontinued due to: 3/7 irregular use, 2/7 vertigo, 2/7 hypercalemia and acute renal failure recovered after withdrawn the drug. During the use of enalapril we did not observe significant difference in potassium or creatinine serum levels, as well as blood pressure measurements.

Conclusions: The use of enalapril in pediatric patients with renal disease and proteinuria/ microalbuminuria showed security and efficient. Therefore, we suggest it as a antiproteinuric and renoprotective agent in children.

A. Filleron, AL. Adra-Delenne, L. Ichay, F. Dalla-Vale, H. Valette, D. Morin CHU Montpellier, Pediatric Nephrology, Montpellier, France In order to evaluate the long-term efficacy of oral cyclophosphamide (CP) in children with SDNS, the outcome of 33 patients (11 girls) treated in our unit for steroid sensitive NS were studied retrospectively. Median age at diagnosis was 3.8 years (range 1.5 to 13). Initially, they received oral prednisone (P) : 60 mg/m 2 /d for 4 weeks and P dosage was then tapered for the next 14 weeks (totale dose P: 3390 mg/kg). Relapses of proteinuria were treated with P (60 mg/m 2 /day) and, in case of steroid dependency (SD), P was maintained on an alternate day regimen. One single child had no relapse, while 8 had a relapse rate of less than 1/year. The remaining 24 frequently relapsed and 14 received oral CP -2 mg/kg/day for 12 weeks, totale dose 168 mg/kgbecause of their high relapse rate with steroid toxicity. Median duration of P treatment was 3.7 years (range 0.75 to 10) before CP was given. In one case CP had to be stopped because of hemorragic cystitis. Follow-up after CP treatment was, at least, 2 years. P was stopped in the following 6 months after CP in 10/13 children, but has to be continued in the remaining 3 because of early relapse of proteinuria. Among those 13 children, only one had no more relapse 4 years after CP. In 12 children, relapse of proteinuria occured 11.5±7 months after CP. In those patients, 8/12 had to receive another steroid sparing drug such as cyclosporine or mycophenolate mofetil (MMF) because of recurrence of SD. In our experience, CP treatment in NS with steroid toxicity is associated with a significant change in the relapse rate in only 5/13 children and in the remaining 8, improvement was transient. Our results suggest that alternative treatment, such as MMF, has to be evaluated as first-line steroidsparing agent in those patients with SDNS and steroid toxicity.

Interleukin - The aim of our investigation is to compare the concentration of total IgE, specific IgE, interleukin-4 (IL-4) and gamma-interferon (gamma-IFN) in serum of 27 children with initial and relapsed steroid-sensitive MCNS and of 26 children with atopic dermatitis at the age from 1 to 16 years. The concentration of total IgE was measured by immunoenzymatic method and IL-4, gamma-IFN by immunoassay technique using monoclonal antibodies. The result showed that 64% of 26 children with atopic dermatitis had the increased concentration of total IgE; specific IgE was increased to alimentary allergens-84,6%, household-69,2%, inhaled-26,9%. The concentracion of IL-4 was 34,4±9,4 pg/ml, of gamma-IFN was 102±11,3 pg/ml. The result showed that 9% of 27 children with MCNS had increased concentration of total IgE; specific IgE was increased to alimentary allergens-96,2%, household-77,8%, inhaled-29,6%. The concentration of IL-4 was 22,31±3,8 pg/ml, of gamma-IFN was 91,97±9,3 pg/ml. According to our investigation, the concentration of IL-4 and gamma-IFN in children with MCNS were not significantly different then in children with atopic dermatitis. Conclusion: the fact that there were not significant differences in serum total IgE and specific IgE, IL-4 and gamma-IFN in children with MCNS and atopic dermatitis gives us a reason to suppose that these diseases have identic mechanisms of pathogenesis with IgE reaction I-type with activation of T-limfocyte. To clarify the pathogenesis of MCNS, comprehensive studies for these cells would be worthwhile. There are several lines of evidence that the slit diaphragm (SD) not only serves as a structural framework for filtration barrier but also has an essential role as a signaling platform. Nephrin is tyrosine phosphrylated by Src-family tyrosine kinase, Fyn. Phosphorylated Nephrin recruits Nck to SD, and regulates assembly of actin filament. The crucial roles of tyrosine phosphorylation in podocyte is also indicated by renal malfunction observed in Fyn knockout mice. Neph1 has a longer cytoplasmic domain and a larger number of tyrosine residues in its cytoplasmic region than Nephrin. But knowledge about tyrosine phosphorylation of Neph1 is limited. Here we characterize Neph1 as a substrate of Fyn. Fyn interacted with and phosphorylated cytoplasmic domain of Neph1 in vitro and in cultured cells. Peptide mass fingerprinting of Neph1 cytoplasmic domain phosphorylated by Fyn in vitro identified at least five tyrosine phosphorylation sites. Site-directed mutagenesis confirmed that these tyrosine residues were indeed phosphorylated in cultured cells. In pull-down analysis with Neph1 from rat glomerular lysate, Neph1 specifically bound to an adaptor protein Grb2 and a tyrosine kinase Csk in a phosphorylation-dependent manner. Coimmunoprecipitation experiments revealed phosphorylation of Y637 and Y638 were crucial in Neph1-Grb2 binding. Furthermore, tyrosine phosphorylated Neph1 suppressed ERK activation elicited by Fyn, and also inhibited Fyn-induced AP-1 transcriptional activation. These inhibitory effects required the intact binding motif of the Grb2 SH2 domain, and both Y637F and Y638F mutants failed to inhibit ERK activation. These results indicate that Fyn orchestrates a wide spectrum of protein-protein interactions at SD by phosphorylating Neph1 as well as Nephrin, and Neph1 modulates downstream signaling by phosphorylation-dependent association with adapter proteins.

Celiac disease (CD) is a common disorder in southern Europe and has a protean clinical presentation. HLA class II aplotypes DQ2 and/or DQ8 are present in 99% of CD patients and in 30% of the normal population. The observation of three patients with both CD and nephritic syndrome (NS) prompted us to study HLA class II aplotypes in our patients with NS. In all children with NS admitted to our Unit we determined the presence of DQ2/DR3, DQ2/DR7, DQ2/DR4 e DQ8/DR4 aplotypes and anti-transglutamidase antibodies (ab-htTG). HLA typing was done by DNA extraction and PCR amplification and electrophoresis in agarose; ab-htTG determination was made by ELISA. As control groups we examined 27 children with CD and 70 first degree relatives (of theirs).

In so far we have studied 40 children with NS (27 males, 13 females, age ranged 3-18 years); 34 are steroid sensitive (SSNS), 6 steroid resistant (SRNS). A renal biopsy was done in 10 and showed minimal lesions in 3, focal and segmental sclerosis in 2, membranoproliferative gn in 2, membranous gn in 2 and IgA deposition in 1. Corticosteroids or other immunosuppressant were administered in 27 when blood was drown. DQ2 and/or DQ8 aplotypes were present in 33 out of 40 patients (82.5%), in 29 out of 34 SSNS (85.3%), in 43 out of 70 CD relatives (61%) and in all CD patients. DQ2/DR3 combination was present in a smaller percentage of NS compared to control groups. Ab-htTG were detected in one patient out of 26 (3.8%). Purpose: to investigate activity of antithrombin and a protein C at 57 children with MCNS: at 39 active period (proteinuria more 1 g/m 2 /d; hypoalbuminemia <25 g/l), at 46 in incomplete remission (the third day of absence of proteinuria, hypoalbuminemia <35 g/l), at 11 in proof remission. Methods: activity of natural anticoagulants in blood was defined by a clotting method with use of reactants "Roche" and "Behring".

Results: Activity of antithrombin in blood in the active period of disease sharply decreased (60,6±3,9%, p<0,0001), and already in the period of incomplete remission came back to norm (96,2±2,6%), characteristic for the period of full remission (96,3±4,8%). Activity of a protein C in blood in the active period of MCNS was high (154,1±7,5%, p<0,001), during incomplete remission decreased (127,1±7,5%, p<0,001), in the period of proof remission was in norm (94,2±5,7%, p<0,001). At children with MCNS dependence of decrease in activity antithrombin from weight hypoalbuminemia (r=0,5, p<0,005), hyperfibrinogenemia (r=-0,6, p<0,005), hypercholesterolemia (r=-0,5, p<0,01) and hyper-lipoproteinemia (r=-0,5, p<0,03) is established. Authentic distinctions of factor of the attitude of activity of protein C/ activity of antithrombin depending on the period (the active period -2,5, incomplete remission -1,3, proof remission -0,98) are received. Conclusion: at children with MCNS changes in system of natural anticoagulants: decrease in activity antithrombin below 80% and increase of factor of a parity of anticoagulants (more than 1,0) testify to hypercoagulation and risk of thrombosis.

Varicella Objectives: The pattern of steroid responsiveness of nephrotic syndrome may change during the course of the disease in children with steroid sensitive nephrotic syndrome (SSNS) and/or in different populations. Patients and Results: A prospective cohort study was conducted in 22 centers. Patients who were initially diagnosed as SSNS in 2001 and followed for five years were included. Standard questionary forms from 268 children(149 boys) with a mean age of 4.3 years (22 months-16 years) at presentation were submitted for entry to Data Coordinating Center. 165/268 patients who showed initial steroid sensitivity with a follow-up period of at least one year (1-5 years) were included in the study. Seventy three (44.5%) children remained in sustained remission at 1 year; nine patients showed steroid resistance. 67/165 patients were followed for 5 years, whose clinical course were sustained remission in 46 (70%) and steroid resistance in 4(6%). Steroid response rate from 1 to 5 years remained stable (93-95%). Eight children out of totally 13 patients who were steroid sensitive initially, became steroid resistant in the first year. The remainder showed steroid resistance at the 2 nd year (2), at 4 th year (1) or at 5 th year (2) . Renal biopsy was performed in 19 children who developed steroid dependency or steroid resistance. Nine patients revealed FSGS, 8 minimal change disease, 1 mesangioproliferative GN, 1 membranoproliferative GN, one IgM nephropathy. Only two patients who had minimal change nephropathy in initial biopsy progressed to FSGS after 2 and 5 years. Conclusion: Steroid response rate was between 93-95% and steroid resistance was 4-6% in 5 years follow-up. Secondary steroid resistance within the first year of presentation seemed to be predictive for their subsequent courses. The need of biopsy was not high. SSNS seemed still as a relatively benign condition in our population. The aim of this study was to asses the changes in coagulation/fibrinolysis system in chronic renal disease (CRD) by measuring plasma levels of von Willebrand factor (vWF) and plasminogen activator inhibitor -1 (PAI-1). We studied 74 children (5-16 years old) with nephrotic syndrome (NS): minimal change disease (n=14), focal segmental glomerulosclerosis (n=17), mesangioproliferative glomerulonephritis (n=24), membranoproliferative glomerulonephritis (n=7). Relapse of the disease was observed in 34 patients. 15 healthy age matched children served as controls. Serum levels of PAI-1: Ag and vWF were measured by ELISA. Results. PAI-1 and vWF levels were elevated in all morphological forms of NS in relapse and remission compared with controls (p<0,01) except the MCD remission in which they were the same as controls (p>0,05). The highest levels of PAI-1 and vWF were discovered in relapse of proliferative forms (MesPGN, 70±31 ng/ml and 5,0±1,7 ME/ml, respectively; MPGN, 100,05±61,1 ng/ml and 3,14±0,65 ME/ml, respectively) compared with nonproliferative (MCD 52,98±24,03 ng/ml and 1,81±0,54 ME/ml, respectively; FSGS 52,27±20,39 ng/ml and 2,42±0,84 ME/ml, respectively, p<0,001). Conclusion. These data suggest activation of coagulation/fibrinolysis system in relapse of NS and the absence of normalization in the remission phase. Our results confirmed that more severe fibrin formation via activation of intraglomerular coagulation and fibrin accumulation is characteristic for MPGN, likely by deficiency of the fibrinolysis system.

Introduction. Several recent case reports suggest that Rituximab (RTX) could be an effective treatment for idiopathic nephrotic syndrome. In a retrospective study, data were collected from 11 patients (mean age: 12.6 years) treated with RTX for steroid dependent nephrotic syndrome (mean duration of the disease: 112 months). Four of 11 were treated during a remission period. Eight of 11 were treated in association with one or several other immunosuppressive (IS) treatments (prednisone, anticalcineurin, mycophenolate mofetil). RTX efficacy was admitted when the previous IS treatment was withdrawn or significantly tapered-off, or when the proteinuria disappeared with no other change than RTX treatment.

A complete B-cell depletion was confirmed in all patients when assessed (9/11) even when RTX was infused during a period with nephrotic proteinuria. RTX was considered to be effective in 6 cases especially when given in association with other immunosuppressive treatment during a period with remission of proteinuria (4/4 success, follow-up 3 to 10 months). Conversely RTX failed to induce remission among patients who were treated during a proteinuric period with no other immunosuppressive drug (3/3 failures). Finally RTX was considered to be effective among 2 of 4 patients treated in association with other IS drugs during a proteinuric period (follow-up 3 and 31 months). There was no significant side effect during RTX infusion. Delayed side effects were observed for 2 patients: 1 case of neutropenia and pneumocystis pneumonia and 1 case of hypogammaglobulinemia.

Conclusion. RTX is an effective treatment in a subset of patients with severe steroid dependent nephrotic syndrome. Further prospective data are necessary to determine if RTX could become an alternative to other immunosuppressive drugs in patients with toxic side effects.

Infections are leading causes of death in lupus patients. Disseminated histoplasmosis has been commonly documented in immunocompromised patients including lupus patients. We report a case of lethal cerebral histoplasmosis in a child originating from French Guyana. Lupus disease was revealed by typical malar rash. She developed a class II lupus nephritis treated with prednisone and azathioprine. Then she developed restrictive lung disease, recurrent arthritis and pericarditis. Later on, nephrotic syndrome revealed a class III lupus nephritis treated with methylprednisolone pulses and mycophenolate mofetil. Four years following the onset of the disease, she was admitted because of febrile seizures and five months later for a febrile coma. Repeated lumbar punctures displayed hypercellularity with depressed levels of glucose and elevated protein concentrations but sterile cultures. According to the presence of high titers of lupic specific antibodies and cerebral MRI suggesting vasculitis, neurological flare of lupus was considered and immunosuppressive treatment was increased (methylprednisolone and cyclophosphamide pulses, plasma exchanges). A repeated lumbar puncture evidenced presence of Histoplasma capsulatum. Despite antifungic treatment the child died. Our report emphazises the difficulty to discriminate opportunistic infections from the wide spectrum of lupus clinical features. Symptoms of infection may mimic those of lupus, or conversely, may be masked by immunosuppressive drugs. Infection screening should take in account clinical feature as well as endemic context. Our report is the first case of isolated cerebral histoplasmosis in a child with systemic lupus.

Renal manifestations of mitochondrial cytopathies have been described, but nephrotic syndrome with respiratory chain disorders (RC) was described extremely rarely in infancy. We report a 9 months-old boy with a mitochondrial cytopathy preceded by 2 months history of steroid-resistant nephrotic syndrome. On admission his clinical condition was deteriorating rapidly with gross oedema, ascites, hypertension and oliguria. Fundoscopic examination revealed salt-pepper sign which was thought to be consistent with intrauterine infection (IUI) at that time. However, serologic and microbiologic investigation of IUI was inconclusive. A sensorineural hearing loss was found to associate his findings. Podocin mutation was negative. A percutaneous renal biopsy was undertaken and revealed diffuse mesengial sclerosis. A significant decrease in mitochondria was observed on electron microscopic examination. The child progressed to end stage renal failure and was successfully managed by peritoneal dialysis. During his follow-up a fine tremor was observed in his hands and cranial MRI revealed demyelinisation in left thalamus and occipital lobe. Steroid resistant nephritic syndrome, sensorineural hearing loss, ocular and neurologic findings has led us to be suspicious about mitochondrial cytopathy and muscle biopsy was done. Though muscle biopsy was normal, the results of biochemical analysis showed a deficiency of the respiratory chain complex IV (cytochrome c oxidase) (RC IV). The clinical phenotype and the deficiency of respiratory complex IV thought to be compatible with deficiency of the cytochrome c oxidase deficiency protein COX10. Nephrotic syndrome with RC disorder were described extremely rarely in infancy. Based on these observations, we suggest that RC disorders should be considered in patients with early onset nephritic syndrome. Human parvovirus B19 (HPVB19) was identified as the cause of a self-limited childhood febrile illness with rash, namely erythema infectiosum. Most of HPV-B19 infections are usually mild or asymptomatic, but in some cases infection is associated with serious systemic complications. Renal involvement in patients with HPVB19 infection was discussed in recent, mostly anecdotal, case reports. The majority of these reports were described in adults, whereas only a few cases of childhood were defined whom presented with mesangiocapillary proliferative glomerulonephritis, FSGS or tubulointerstitial nephritis. A literature search revealed no cases of acute endocapillary proliferative glomerulonephritis in childhood. A 10-year-old girl was admitted with fever, cough, maculopapuler rash, hemoptysis, dark-colored urine, multiple lymphadenopathies, hepatosplenomegaly. She developed acute nephritic syndrome during the course of this complex clinical features. Laboratory data showed proteinuria, hematuria, hypocomplementemia, the presence of IgM and IgG antibodies to HPVB19 and positive reaction of serum HPVB19 DNA using a polymerase chain reaction. Renal biopsy showed acute endocapillary proliferative glomerulonephritis with coarse granular C3 depositions in a "starry sky pattern" which is more peculiar to poststreptococcal glomerulonephritis. Electron microscopy revealed subendothelial and hump-shaped subepithelial dens deposits. There was no evidence of either a mycobacterial or a streptococcal infection and the diagnosis of Goodpasture syndrome and connective tissue disorders were excluded by clinical and laboratory investigations. Based on the literature review, this case represents, to our knowledge, the first time that a direct relationship between parvovirus infection and acute endocapillary proliferative glomerulonephritis has been demostrated in a child. Objective: The purpose of this retrospective cohort study was to report the clinical course of children and adolescents with Focal Segmental Glomerulosclerosis (FSGS) according to steroid response.

Methods: The records of 88 patients with biopsy-proven FSGS admitted between 1972 and 2005 were retrospectively reviewed. Demographic, clinical and laboratory data at entry and at the end of the follow-up were analyzed. The patients were classified according to the initial prednisone response into two groups: Group 1 (G1): response (complete or partial remission) (n=63) and Group 2 (G2): non-response (prednisoneresistant) (n=25). Renal survival analysis was performed using the Kaplan-Meier method.

Results: The median age at admission was 4.55 years (IQ range: 0.99±12.84 yr) in G1 and 6.86 years (IQ range: 1.08±15.55 yr) in G2. Seventeen patients (27%) of G1, and 17 patients (68%) of G2 presented with hematuria at admission, and 31 (49%) children of G1 and 13 (52%) of G2 presented blood pressure levels above the 95th percentile. G2 presented a higher 24 h proteinuria (4.87 mg/24 h) at admission when compared to G1 (3.17 mg/24 h, p=0.019). Median follow-up time was 8.72 years in G1 and 3.96 years in G2. The renal survival rate was 98% at 5 years and 92% at 12 years in G1, 69% at 5 years and 26% at 13 years in G2. Conclusion: Progressive renal insufficiency was more frequent in patients with FSGS who have initial resistance to prednisone therapy. Objectives of the study: Adults with chronic kidney disease (CKD) show impaired immune status. In this study, the profile of mononuclear cell subsets was related to the age and actual GFR in children and compared to healthy controls. Methods: The expression of lymphocyte surface antigens was evaluated on peripheral blood (PB) mononuclear cells using three-color flow cytometry in 45 children with CKD (stage2-5) on conservative treatment. We analyzed absolute and relative numbers of total leukocytes, total lymphocytes and subsets: CD19+, CD3+, CD3+CD4+, CD3+CD8+, CD3-CD16/56+, CD3+HLA-DR+, CD3+CD25+, CD69+, CD3+αβ+, CD3+γδ+, CD45RA+, CD45RA+CD4+, CD45RA+CD8+, CD45RO+, CD45RO+CD4+, CD45RO+CD8+, CD4+CD25+.

Results: In younger CKD children (below 10 years) absolute numbers of CD3+, CD3+CD8+, CD3+CD25+, αβ+T, γδ+T cells and CD4/CD8 ratio was higher, the percentage of CD3+CD8+, CD45RA+CD4+, CD45RO+CD4+, CD45RO+CD8+, αβ+T cells and the absolute number of CD45RO+CD8+ cells was lower than in the oldest group. In children with the lowest GFR (below 15 ml/min) the percentage of CD3+, CD19+ was lower, the absolute number of CD3+CD25+, CD69+, and the percentage of NK-cells, CD3+CD25+, CD69+, CD45RO+CD8+ cells was elevated as compared to CKD stage 2 group. The absolute number of CD8+, CD3+CD25+, CD45RA+CD8+, αβ+T, γδ+T cells and percentage of total lymphocytes, CD19+, CD3+CD25+, CD69+ was lower in CKD children than in controls. Conclusion: Impaired immune status is observed already in early stages of CKD. Progressive disturbances in PB lymphocytes percentage mostly in the naive and memory T cells and the shift in the CD4/CD8 balance were found in pre-dialysis children with CKD. With progressive loss of renal function, we observed an increased expression of activation markers on T cells such as CD25 or CD69. Introduction: Relapse of steroid resistant nephrotic syndrome (SRNS) after renal graft occurs iñ 30% of the pediatric patients. Medical management is based on increased immunosuppression with the use of IV CyA and plasma exchanges (PE). However, this strategy fails in ~30% of the treated patients. New immunosuppressive agents may improve the outcome of relapsing SRNS post transplant. Case report: A 15-year-old boy with SRNS reached ESRD and received a cadaveric kidney transplant after two years on hemodialysis. The immunosuppressive regime was CyA, MMF and steroids. Seven days post transplant gross proteinuria (4 g/day) reoccurred. IV CyA was administered over two months (blood level: ~450 ng/ml) associated to pefloxacine and PE (n=15), and followed by oral cyclophosphamide (CyP), resulting in partial disease control. CyP was discontinued due to haematological toxicity after one month. Proteinuria increased again from 1 to 3 g/day within 3 months, despite high dose oral CyA (10 mg/kg/day) and MMF. Etanercept (a TNF blocking agent) was introduced at a dose of 25 mg twice weekly (combined with three steroid pulses) and maintained over two months: proteinuria decreased to 0.4 g/day over 20 days. Etanercept was discontinued followed by a relapse of the NS and re-introduced eight months later, with, again a significant decrease of proteinuria to a baseline level of 0.5 g/day. Conclusion: Treatment with anti-TNF agents in nephrotic children has been reported once in a boy with high degree steroid dependent NS; a spontaneous decrease of disease activity over time cannot be excluded in this patient and might jeopardize data interpretation. Our case is the first report of successful antiFtreatment despite a constantly high activity of the nephrotic syndrome, demonstrated by relapse after discontinuation of etanercept while the patient was on post transplant immunosuppression. Fournier´s Gangrene (FG) is defined as a specific, quick and progressive form of synergic necrotizing fasciitis of multi-bacterial origin that affects perineum muscular fascia, genital region and surrounding areas with skin gangrene due to thrombosis of subcutaneous blood vessels. It describes the clinical case in a male preschooler of four years of age with idiopathic nephrotic syndrome (NS) that subsequent presented FG of the scrotum. Broad-spectrum antibiotics, intravenous albumin and surgical cleaning of the scrotal necrotic tissues were indicated. Pseudomona aeruginosa was isolated from necrotic tissue cultures. The later evolution was satisfactory with healing of the affected area and remission of the NS subsequent to the steroidal treatment. FG is an uncommon in children, rapidly progressive infection of the genital, perineal and perianal regions. It is characterized by a synergistic necrotizing fasciitis leading to thrombotic occlusion of small subcutaneous vessels and development of gangrene. Until now few cases have been report FG in children, and still less associate to the kidney diseases. et all (1999) described a 10-year-old boy presenting with steroid resistant NS developed FG of the scrotum so that to our knowledge, this patient seems be the second case reported in medical literature with both pathologies. High index of suspicion, prompt diagnosis, broad spectrum antibiotics followed by wide debridement is the key to successful treatment. Objectives of study: To evaluate a long term experience on IgA nephropathy (IgAN) presenting in childhood and investigate clinical and histological factors that may act as early markers of renal disease progression. Methods: Retrospective review of data from children and adolescents with biopsy proven IgAN in the last 16 years. Demographic and clinical data at presentation and severity of renal histological involvement were recorded and related to renal dysfunction markers identified at the last review. Results: Twenty-five patients were studied (19M/6F) with median age at onset of 11 (7-18) and follow-up of 6 (1-16) years. On presentation recurrent macroscopic hematuria was present in 19 patients, microscopic hematuria (mH) in 6, proteinuria in 11 (1 nephrotic), hypertension in 10 and transient acute renal failure in 1. Renal histology findings were focal mesangioproliferative in 17, focal proliferative in 3, diffuse proliferative in 3 and focal sclerosing glomerulonephritis in 2. Six patients showed tubulointersticial and extraglomerular vascular lesions (TEVL) with glomerular crescents in 2. On follow-up, 7 patients remitted (2 spontaneously, 5 with ACE inhibitors). Of the remaining, 14 were kept on ACE inhibitors due to proteinuria (7), hypertension (1) or both (6). One patient (with focal glomerulosclerosis and TEVL) developed ESRD within a year after diagnosis, despite treatment. At last review, 6 patients presented progressive renal disease with a mean decrease of 6 mL/min/1,73 m 2 in GFR per year. These (5M/1F) showed mainly mH and proteinuria at onset and TEVL. Conclusions: Early renal function impairment in childhood IgAN can occur and may be associated with mH and proteinuria at presentation and with focal glomerulosclerosis and TEVL on renal histology. Proteinuria persistence in a number of patients emphasizes the need for long term followup into adulthood.

Adhesion Molecules, IL-12+p40 and CD23+CD19+ and CD25+CD4+ Lymphocyte Subsets in Childhood Nephrotic Syndrome Background: Parathyroid hormone (PTH) can modulate T cell activation and proliferation through as yet incompletely identified mechanisms. Since the PTH receptor (PTHR) is a G protein-coupled receptor and thus a candidate for association with lipid rafts, and since PTH has been shown to alter membrane phospholipid metabolism, we explored the relationship of the PTHR with lipid rafts in human T cells. Methods and Results: We found by flow cytometry that neither physiologic nor pathologically elevated concentrations of PTH affect the up-regulation of the raft marker GM-1 or of the partially raft-associated activation marker CD25 in purified T cells stimulated with phytohemagglutinin (PHA). Moreover, we detected the PTHR exclusively in non-raft fractions of these cells after sucrose gradient separation. Conclusions: These data indicate that in human T cells, the PTHR does not associate with lipid rafts and that PTH does not modulate these domains. Accordingly, other mechanisms underlying the actions of PTH on human T cells need to be sought.

The direction and magnitude of potassium transport in nephron segments depend on the sitespecific distribution of transporters in tubule cell membranes. Potassium depletion has been demonstrated to be associated with altered sodium reabsorption in renal tubule segments. We examined whe her potassium transporters protein expression is associated with altered abundance of major renal Na + transporters, that may contribute to the development of hypokalemia in LP. After weaning rats (n=8) were fed 14 days with LP diet (8%), then they were recovered with a normal protein diet (24%, RP), each group had a control group (24%, NP). We examined the changes in the abundance of the Na + /H + exchanger (NHE3), Na + K + ATPase, Na + K + 2Clcotransporter (BSC-1), Na + Clcotransporter (TSC), epithelial sodium channel (ENaC) subunits and ROMK in kidneys of LP, NP, RP rats. Controls were normalized to 1. Results Reduced Clcreat (ml/min) in LP vsNP (0.6±0.2 vs 1.6±0.2), hypokalemia (3.6±0.1 vs 5.1±0.2 mEq/L) and increased FE K+ (44.2±0.5 vs 29.9±0.3%) were demonstrated. Immunoblotting revealed that the abundance of NHE3 in cortex was severely decreased. The amount of BSC-1 (1.9±0.07, p<0.05) and TSC (1.4±0.15, p<0.05) protein levels were enhanced in the inner stripe (ISOM) and outer stripe of the outer medulla (OSOM), respectively. ROMK protein levels were increased in LP (1.23±0.04, p<0.05), the protein abundance of the ENaC subunits α, β and γ was increased near 1.25 fold each in response to LP. Na + K + ATPase protein levels showed no differences in cortex and OSOM. After RP, Na + transporters expression returned to control values. Conclusion: Increased expression of BSC-1, TSC, ENaC subunits and ROMK, contributing to distal potassium secretion was shown in hypokalemia from LP. A role of Aldosterone may be suggested.

V. Belostotsky 1 , MZ. Mughal 2 , J. Berry 3 , N. Webb 1 1 Royal Manchester Children's Hospital, Pediatric Nephrology, Manchester, United Kingdom 2 St. Mary's Hospital, Pediatrics, Manchester, United Kingdom 3 Manchester Royal Infirmary, Vitamin D Laboratory, Manchester, United Kingdom Aims: To describe the prevalence of vitamin D deficiency in South Asian and white UK children with renal disease. To establish how decreased levels of vitamin D affect PTH in patients with a normal GFR. Methods: 143 children aged 1-18 years were enrolled in the study: 99 were of white UK, 38 of S Asian and 6 of other ethnic origin. 18 were on dialysis, 18 had chronic renal failure, 46 had various renal disorders with normal GFR (>80 ml/min/1.73 m 2 ), 61 had a transplant (42 with anormal GFR). Blood samples were collected to establish the levels of 25-vitamin D (25-OHD); PTH; Creatinine. 25-OHD concentration <10 ng/ml was defined as vitamin D deficiency; levels between 10-20 ng/ml as vitamin D insufficiency. Serum PTH of 0.8-3.9 pmol/l was defined as normal.

Results: The prevalence of vitamin D deficiency/insufficiency was higher in S Asian (87%) than White (36%) children (p<0.0001). Ofthe 88 (28 S Asian, 56 White and 4 other) children with normal GFR17/28 S Asian and 28/56 White children had PTH concentrations >3.9 pmol/l. Of these 12/17 S Asian, 11/28 White children had low levels of 25-OHD (P=0.04). Of 19 transplant patients with reduced GFR, 11 of 14 with a high PTH had low 25-OHD levels, compared with 1 of 5 with a normal PTH (p=0.04). Conclusions: Many S Asian children attending our renal clinic are vitamin D deficient/insufficient and the prevalence of this problem is significantly higher than that in the white population. High PTH values in the setting of a normal GFR can often be explained by vitamin D deficiency and should result in serum 25-OHD levels being measured.

Nephronophthisisis a rare recessive autosomal disease which may be either limited to progressive chronic tubulointerstitial nephritis or associated with extrarenal involvement (eye, liver, central nervous system, etc.); mutations/deletions have been found in at least 6 NPHP genes. Fibrous dysplasia is a benign skeletal lesion due to an activating mutation inthe gene that encodes the α subunit of stimulatory G protein and occurs after fertilization in somatic cells; it involves one or several bones and may be part of McCune Albright syndrome. We report on a boy with fibrous dysplasia of bone diagnosed at 3 yrs of age, who underwent protocol renal function tests at 7 yrs of age in the follow-up of pamidronate treatment. Inulin clearance was 75 mL/min/1.73 m 2 and potassium reabsorption rate was 55.2% where as there was neither urinary phosphate wasting nor hypercalciuria. Serum magnesium was decreased (0.74 mmol/L) without reabsorption abnormality and serumuric acid progressively increased with age. In addition, due to increasing microalbuminuria, a treatment with ACEi was started at 11 yrs of age. Renal ultrasonography at 11 yrs of age showed hyperechoic reduced-sized kidneys with few microcysts. A renal biopsy (light and electron microscopy) was performed at 11 yrs of age, which showed nephronophthisis-like lesions, i.e., diffuse interstitial fibrosis and focal thickening of tubular membrane basement. DNA analysis revealed no NPHP1 gene deletion but is still under investigation.Nephronophthisis has been reported in association with skeletal involvement (coneshapedepiphyses) and fibrous dysplasia with hypophosphatemic rickets or Fanconi syndrome. However no association between fibrous dysplasia of bone and nephronophthisis-like lesions has been described and may be a new picture of the nephronophtisis/medullary cystic kidney disease complex. M. Bald, M. Holder, H. Leichter Olgahospital, Pediatric Nephrology, Stuttgart, Germany Puumalaviruses belong to the group of Hanta viruses and are transmitted by inhalation of aerosolized particles of the red bank vole (Cletriomonysglareolus) which is endemic in the Alb-Danube region of Southern Germany. Infections with Puumala virus were first described as "Nephropathia epidemica" in Scandinavia with the clinical symptoms of fever, thrombocytopenia and acute renal failure. Over the last seven years three boys with acute renal failure were admitted to our hospital after vacationing in the region endemic for Puumalavirus. All three presented with high fever, influenza like symptoms aswell as pronounced abdominal or flank pain. They showed a decreased GFR (14, 47 and 71 ml/min/1.73 m 2 , respectively) with hematuria and proteinuria. CBC revealed no leucocytosis or anemia, but thrombocytopenia in 2 of the 3 patients. They had no oliguria, but 2 patients had marked polyuria in the recovery phase of renal function. Arenal biopsy in the boy with the most severe presentation showed diffuse tubular damage. Puumala virus infections were confirmed in all patients by serological tests, and renal function normalized within 2-3 weeks. Nephropathia epidemica due to Puumala virus infections have to be included in the differential diagnosis of acute renal failure in patients from endemic regions. Severe abdominal or flank pain are common symtoms in these patients; renal failure is transient and the general prognosis is good. Aims: The objective of this study is to determine the relationship of urinary calcium excretion (UCa) with sodium and protein intake in a pediatric population of families with low income. Methods: 109 children, 59 F and 50M, ages 8 to 15 years from families with income <$100/month were studied. Protein intake was estimated with a 7-day dietary record. A nonfasting urine sample was collected for dipstick, calcium, creatinine, sodium, potassium, urea and uric acid. Urinarycalcium/creatinine (Ca/Cr), sodium/potassium (Na/K), uricacid/creatinine (AU/Cr) and urea/creatinine (U/Cr) ratios were calculated. Children with a urinary Ca/Cr >0.20 mg/mg, were submitted to a 15 day period of high sodium foods restriction after which a second urine sample was collected. Results: Mean (X) and standard deviation (SD) for Ca/Cr, Na/K, AU/Cr and U/Cr ratios were: 0.09±0.05 mg/mg, 5.68±5.41 mEq/mEq, 0.5±0.24 mg/mg and 16.12±5.3 mg/mg respectively. The 95th percentiles for Ca/Cr, Na/K, AU/Cr and U/Cr were 0.19, 13.07, 0.96 and 26.5 respectively. X±DS for protein intake was 1.27±0.27 g/kg/day. The incidence of hypercalciuria was 6.4% in the initial urine sample and 2.7% in the second. Correlation was significant between Ca/Cr ratio and Na/K ratio (r: 0.5, p<0.05), AcU/Cr ratio (r: 0.38, p<0.05) and U/Cr (r: 0.30, p<0.05), not significant between Ca/Cr ratio and protein intake. Conclusions: The incidence of hypercalciuria in this serie is lower than previously reported values in Venezuela for the general pediatric population and decreases further when sodium intake is controlled. Although no correlation was found between UCa and protein intake, we could speculate that protein intake near to the daily recommended requirements of 1 g/kg/day, could be a possible reason for the lower incidence of hypercalciuria in this population. 16-year old girl presented with rapid onset of muscular weakness and a short history of severe dysphagia, dysphonia nad significant wasting. On examination, she was dystrophic (BMI 15,7) and had signs of myopathy. Laboratory findings confirmed myopathy (CPK 106,4 ukat/L, AST 2,86 ukat/L, myoglobin 1582 ug/L). There was striking hypokalemia (S-K 1,8 mmol/l) suggesting hypokalemic paralysis. Diagnosis of distal renal tubularacidosis (dRTA) was based on confirmation of hyperchloremicmetabolic acidosis, severe hypokalemia, high urinary pH and positive value of urinary anion gap (S-Cl 120 mmol/l, pH 7,31, BE 10, urinary pH 7,5). There was evidence of other signs of renal tubular impairment (urinary beta-2-microglobulin 213 mg/l, glomerulo-tubular proteinuria 1,01 g/24 h). Autoimmune tests (high positive rheumatoid factor, ANF, ENA ss-A/Ro, ss-B/LA, high circulating immunocomplexes) and low values of sialometric measurements (7,5 ml/2x15 minutes) revealed primary Sjogren´s syndrome as the underlying cause of dRTA. The renal biopsy confirmed chronic tubulo-interstitial nephritis compatible with this diagnosis. Full recovery of muscle weakness and laboratory findings of hypokalemia and acidois followed potassium and alkali replacement. Corticosteroids were administered with subsequent addition of cyclosporine A because of disease activity. Conclusion: primary Sjogren´s syndrome is a rare diagnosis in childhood and adolescence and should be considered in patients presenting with hypokalemic paralysis due to dRTA.

M. Caletti, H. Lejarraga, S. Caíno, A. Jiménez

Introduction: NDI is a chronic, genetic disease caused by an inability to effectively conserve urinary water, due to a lack of response of distal renaltubule to antidiuretic hormone. The main symptom is polyuria, polydipsia and growth impairment. Objective: to evaluate long term growth in height and weight of 16 children with NDI. Patients and methods: Sixteen patients with NDI attending hospital for a median period of 11.5 years (range 3.4/16.2 yrs) were studied. Treatment consisted of Indometacine, hydroclorotiazide and amiloride (IHA). Height and weight was measured with standardized anthropometric techniques. Z scores(SDS) for all measurements were calculated according to national standards. Results: All children responded favourably to treatment. Mean birth weight SDS was not different from zero; mean height and weight at diagnosis was ±2.31 and ±2.66 SDs respectively, and at the end of follow-up was ±1.30 and ±0.98 respectively. The majority of patients´s growth curves evolved below the 50 th centile. Ten out of 16 children experienced some catch up in height (mean height gain: 1.38 SDs (r: -0.50/2.42)). Mean weight gain during follow-up was 1.74 SDs (r: 0.86/4.24) . Mean gain in body mass index was 1.72 SDs (range 0.5/4.8). In the two patients who attained adult height, adolescent growth spurt was normal, and final height was within normal limits for standards and for parental height. Correlation coefficient between gain in height andage at diagnosis was ±0.58. Conclusion: although mean height at follow-up was below the expected normal value, combined therapy with IHA is compatible with some catch up growth in height and weight. The lower the initial height, the greater the height gain. Adherence to treatment is essential for normal growth in children with NDI.

Body Growth of Children with Steroid-responsive Idiopathic Nephrotic Syndrome M. Noer, I. Irwanto, N. Sumiarso, M. Chalim Soetomo Hospital, School of Medicine Airlangga University, Department of Child Health, Surabaya, Indonesia Objectives of study: The present study was designed to evaluate the statural growth of children with steroid-responsive idiopathic nephrotic syndrome, attending the Pediatric Nephrology Unit Department of Child Health, School of Medicine Airlangga University, Soetomo Hospital, Surabaya, Indonesia, with a minimum follow-up of 2 years. Methods: Anthropometrice valuation included weight, height, and growth velocity expressed as mean and standard deviation scores (SDS), relative to the normal population (NCHS/CDC 2000). These indices were analyzed at admission and then every 6 months of follow-up. All patients were treated with prednisone, according to Indonesian Consensus of management of idiopathic nephrotic syndrome in children. Results: Of 157 children (105 boys and 52 girls), 43 patients (34 boys) aged 26/12 years to 16 years (mean 7.05 years) were analyzed. Initial mean height and Z score (height for age) were 108.41±15.2 cm and -1.85±1.41, respectively. Mean height and Z score (height for age) of the last follow-up were 121.88±15.1 cm and -1.34±1.5, respectively. Mean growth velocity were 6.25±2.05 cm/year where 3 boys (6.9%) had growth velocity less than 4 cm/year. Total cumulative dose of steroid during 2 years of follow-up were 4283.90±2863.35 mg or 233.76±153.73 mg/kgBW. Conclusions: The cumulative dose of steroid up to 233.76 mg/kg body weight in children with nephrotic syndrome during 2 years of treatment did not influence their growth velocity. Background: Recently it has been reported in adult patients (pts) that deterioration of renal function was associated with the lost of nocturnal blood pressure (BP) dip and enhanced urinary sodium (UNa) and protein (UPRT) excretion during night. Objectives of study: To investigate the circadian rhythms of BP, UNa and UPRT in children with chronic kidney disease stage I (CKD I). Methods: In 34 pts (15 boys) aged 11.2±4.3 years with CKD I (chronic glomerulopathy confirmed by renal biopsy in 85% pts), 24 hour BP was monitored during daytime (d) and nighttime (n) and urinary samples for UPRT, urinary creatinine (UCr), and UNa, were collected for both periods. Results: Serum creatinine-based GFR was 127±22 ml/min/1.73 m 2 , UPRT ranged from 21 to 5455 (median 141) mg/24 h, and UNa from 27 to 267 (median 102) mmol/24 h. In general we found a highly significant nocturnal decrease in systolic BP (from 116 to 108 mmHg), diastolic BP (71 to 62 mmHg), mean arterial pressure (87 to 78 mmHg), heart rate (91 to 75/min) urinary output (UO), UNa and UPRT. The regression equations were as follows: UOd (ml/m 2 /h)=32+1.6xUOn (ml/m 2 /h); UNad (mmol/l)=73.5+0.14xUNan (mmol/l); UPRTd (mg/m 2 /h)=5.4+1.83xUPRTn (mg/m 2 /h) and urinary osmolality (US) d=13+0.65xUSn. Nocturnal decrease of UO correlated with nocturnal decrease of UCr and UPRT, and nocturnal decrease of UPRT correlated with nocturnal decrease of UO. More than half of the patients were classified as non dipper. They differ significantly from dipper only in night/day changes of US. Conclusion: Night/day changes of UO, UNa and UPRT in pts with CKD I may be calculated from the given regression equations. These changes are not correlated with nocturnal BP decrease. Non dippers have greater nocturnal change of US compared to dippers. Follow-up of these parameters will clarify their importance in progression of CKD.

Autosomal Autosomal Dominant Proximal Renal Tubular Acidosis (pRTA) it is described L. G. Brenes (1977) at seven members of one family. We diagnosed seven members of the Afghani family with pRTA: mothers and 6 children (5 girls, 1 boy from 2,5 till 16 years) with hyperchloremic metabolic acidosis. Pedigree analysis suggested an autosomal dominant inheritance pattern. Observable patients did not have ricket and nephrocalcinosis. Deafness and ocular abnormalis are absent. The plasma HCO 3 concentration is decrease in the range of 14,9 to 19,0 mM/L, minimal urine pH is <5,5. Parameters of blood creatinin and glomerular filtration rate were normal. Urine calcium excretion was normal. Therapy strategy of pRTA at observable patients provides high dozes of citrates/bicarbonates 10-15 mmol/kg per 24 h. 

All India Institute of Medical Sciences, Division of Nephrology, Department of Pediatrics

Methods: Retrospective case-search. Data of previously reported prospective trial (n=19) was also included. Results: All except 6 patients had previously been treated with both levamisole and cyclophosphamide. Forty-two cases qualified for the study and were administered MMF for a mean duration of 14.3 months (95% CI, 12.0, 16.6/patient in the first 6 months of treatment and 0.7 episodes (n=35) in next six months of MMF treatment (P<0.0001), an average reduction of 62% (95% CI, 49.1, 75.0) from the pre-MMF phase. Nine (21.4%) patients had no relapses while on MMF therapy

We present sibling cases of AS with heavy proteinuria at early childhood. A boy (3 year-old) and a girl (2 yearold) were diagnosed as X-linked AS. Since a boy developed persistent heavy proteinuria (UP/Cr 2.9) with macrohematuria andresistant to ARB/ACEI therapy, we treated him with cyclosporinA (CsA) that could lead to complete remission. To investigate pathomechanism of proteinuria, we tested immunostaining for slit diaphragm associated molecules (nephrin, podocin), GBMassociated molecules (laminin, perlecan, agrin) and podocalyxin using frozen sections from his firstand second biopsy and girl's one (UP/Cr 0.4). In the specimens from boy's first biopsy and girl's one, light microscopy revealed mild mesangial proliferation and no differences ofthe expression with perlecan, agrin and podocalyxin compared with controls. However, when determined laminin isoforms, fetal type laminin (alpha2beta1gamma1) wasdistinctly observed in the GBM, whereas that was localized only inmesangium with controls. Interestingly when compared mature laminin isoform (alpha5beta2gamma1), beta2 chain was specifically less expressed in the GBM. However there were no differences of expression of these molecules in the specimens between pre-and post-treatmentwith CsA. In boy's second biopsy, 50% glomeruli were detected to becollapsed. Together with the recent report showing that laminin beta2 mutation causes congenital nephrotic syndrome

Factor V Leiden Mutation and Steroid Resistant Membranous Glomerulonephritis: a Case Report M. Buyukcelik 1 , M. Karakok

Turkey Renal Compications of D-Penicillamin Therapy in Wilson's Disease

Sami Ulus Children's Hospital, Department of Pediatric Nephrology

Sami Ulus Children's Hospital, Department of Pediatrics

Sami Ulus Children's Hospital

Hass classification), treatment and outcome. Thirty-nine patients; 29 boys (74.4%) and 10 girls (25.6%) time of the last examination (median 60 months, min<1 year) after the admission as a long term follow-up. Clinically, Group I; while microscopic hematuria was detected in 6 patients, 19 patients had repeated attacks of hematuria, 4 had isolated mild proteinuria/hematuria, Group II; 6 patients had nephritic, 1 had nephrotic syndrome and 3 had both. Biopsy grades in the 39 patients: 55%, 60% had grade I, 10.4%, 10% had grade II, 31%, 20% had grade III, 6%, 10% had grade IV in Group I and II, respectively. Group I and II patients recovered completely (no hematuria and proteinuria) 34.4%, 44.8% as well as 20%, 50%, short-term, longterm, respectively. While recovery rates in fish-oil and/or ACE-inh treatment group was 34.4% and 48.2%, in corticosteroids group, it was 25%, 50% short-term, long-term,respectively. No patients who received immunosuppressive treatment had improved. However, 3 (7.6%) patients would suffer from ESRD. Initial presentation, severity of renal involvement and type of the treatment were not found to have a prognostic value (p>0.05). In children, IgAN is characterized by extreme pathogenetic, clinical and histological polymorphisms

Radojevic 1 1 University of Belgrade, Faculty of Medicine, Institute of Pathology, Belgrade, Serbia 2 Institute of Mother and Child Health of Serbia, Belgrade, Serbia 3 University Children's Hospital, Department of Nephrology, Belgrade, Serbia Celiac Disease HLA Aplotype in Children with Nephrotic Syndrome S

I (IF) or MCP or with anti-CFH autoantibodies. Varicella hasn't been described as a triggering event of aHUS. We report two cases of aHUS associated with complement dysfunction revealed after varicella infection. Case 1. A five year-old boy presented with non post-diarrheal HUS, 17 days after varicella. Serum creatinine was 300 μmol/L, hemoglobin 6.5 g/dl, schizocytes 17%, platelets 19 G/L. Glomerular filtration rate normalized within 14 days. Search for Shiga toxin-producing E coli in the stools and serum anti-lipopolysaccharides antibodies were negative. Plasma C3, CFH and IF levels were normal. No mutations of CFH and IF were found. MCP cell-surface expression was decreased and a C30F mutation in MCP exon 2 was demonstrated. Case 2. A four year-old girl had aHUS 5 days after varicella

At that time, complement system study showed normal C3 level (677 mg/l, normal 660 to 1260 mg/l), normal CFH level (81%, normal 70-130%), but the presence of anti-CFH autoantibodies. No mutations of CFH, IF or MCP were found. In conclusion, these 2 cases outline that varicella can be the triggering event of aHUS associated with complement dysregulation

About 450 (62.5%) children had relapses after initial remission. Various infections were responsible for relapsed with in 200/450 (44.44%) who had relapses. About 120 children (32.69%) relapsed with out cause where as poor compliance was observed in 47 (12.8%). Overall infection and relapse rate was 1.4 and 1.00/pt/yr respectively. Among 367 children with infections, most common types of infections were Acute Respiratory Infections (ARI), Diarrhea and UTI seen in 200 (54.49%), 82 (22.34%) and 30 (8.17%) of cases respectively. Other types of infections like malaria, peritonitis, skin infection and pulmonary tuberculosis were seen

Serum PAI-1 and TGF-beta 1 Levels in Profliferative Forms of Glomerulonephritis in Children

Russian Federation 2 Research Centre for Child Health RAMS, Department of Pathology, Moscow, Russian Federation We aimed to investigate serum levels of plasminogen activator inhibitor -1 (PAI-1) and transforming growth factor-beta 1 (TGF-beta 1 ) in children with proliferative forms of glomerulonephritis (GN). 51 children were examined (5-16 years old) with GN (steroidresistent NS, n=27; steroidsensitive NS, n=11, isolated haematuria, n=13) and 15 healthy age matched controls. Mesangioproliferative GN (MesPGN) was detected in 39 patients, membranoproliferative GN (MPGN) in 12 cases. Serum levels of PAI-1: Ag and TGF-beta 1 were measured by ELISA. Results. The highest levels of PAI-1: Ag and TGF-beta 1 were observed in relapse of MPGN: 93,51±71,63 ng/ml and 16

These results confirm prosclerotic effects of PAI-1 and TGF-beta 1 via increased fibrin deposits and extracellular matrix accumulation in the renal tissue and promotion of disease progression

Rituximab Treatment for Idiopathic Nephrotic Syndrome: a Retrospective Study of 11 Cases V. Guigonis 1 , A. Dallocchio 1 , M. Dehennault

Urinary and Serum Annexin V Levels in Children with Steroid Sensitive and Steroid-resistant Nephrotic Syndrome

Hôpital Robert Debré-APHP, Pediatric Intensive Care Unit

Indonesia This study was aimed to evaluate the efficacy of pulse dose of cyclophosphamide in children with SRNS admitted in Child Health Department Faculty of Medicine University of Indonesia/Cipto Mangunkusumo Hospital Jakarta between 2001-2006. 6-month period, one child died, and the rest (5 children) did not complete the regimen. Five out of 7 children who finished the treatment had remission, while 2 others were still experiencing heavy proteinuria. Remission was achieved in various time, 3 children were in remission after the first dose, in 2 children it was achieved at the third and sixth dose. In further follow-up time; one child remained in remission, one child had relapse when still receiving CPA, 2 children got relapse one month after stopping CPA, and one child had relapse after 6 months ceasing CPA. Nausea and vomiting were found in 2 children

Indonesia This study is to evaluate the anthropometric measurements of children with nephrotic syndrome Methods: A descriptive retrospective study at Child Health Department, Cipto Mangunkusumo Hospital, Jakarta. Data were collected from medical records of nephrotic syndrome

9%) IRNS; Body height and body weight of <P3 was found in none of FRNS/SDNS, 9/32 (28,1%) SRNS, and 20/101 (19,8%) IRNS; BMI >P95 was found in 4/45 (8,9%) FRNS/SDNS, 3/32 (9,4%) SRNS, 4/101 (3,9%) IRNS. Conclusion: The percentage of children with FRNS/DSNS and SRNS with body height <P3

IL-12) during active stage (AS: urinary protein >40 mg/m 2 per hour, serum albumin <2.0 g/dl) and remission stage (RS) in SS-MCNS. A total of 48 patients with SS-MCNS (29 of 48 patients with AS and 19 of 48 patients with RS) and 19 healthy children were recruited for studies. The mean±SD of serum IL-12, sE-selectin and sICAM, levels were significantly higher in patients with AS than in patients with RS (277±188.4/157.2±119 pg/ml; 132.1±67.9/88.3±40.5 ng/ml and 168.3±120.3/82.2±27.1 ng/ml respectively, p<0.05). In spite of, higher levels of IL-12, sE-selectin and sICAM in patients with AS than controls, difference was not statistically important. The percentage of CD3+CD23+ lymphocyte subsets were statistically grater in patients with AS

Severe Proximal Renal Tubular Acidosis in Pearson Syndrome

Birth weight was 4000 g. Pallor was initially noted during the neonatal period and referred to our hospital with anorexia, vomiting, diarrhea, weakness, and increased pallor at 8 wk of age. On the physical examination she was pale and the other systems were unremarkable. Investigation showed hypoplastic anemia, and bone marrow examination showed cytoplasmic vacuolization of both myeloid and erythroid precursors, and maturation arrest of granulopoesis. Family history was negative for hematological disease. The diagnosis PS was considered on the basis of early severe refractory anemia associated with vacuolization of bone marrow precursor cells and ring sideroblasts. Treatment was started consisting of vitamine B6 and folic acid. She was followed with growth retardation, moderate anemia and leucopenia up to age 4.5. At that age, the girl was readmitted with severe vomiting and dehydration. On admission, she had moderate metabolic acidosis, hypokalemia, high plasma lactate, and hypophosphatemia. Further investigations showed tubuler proteinuria, glucosuria, aminoaciduria, and defective bicarbonate reabsorbtion in the proximal tubule. She developed refractory metabolic acidosis resulting in a cardiac and respiratory failure and death. To confirm the diagnosis of PS, molecular studies were performed 4977 bp common deletion was found

Medial Calcification in Intact Human Arteries from Children with Chronic Kidney Disease is Associated with Apoptosis and Osteogenic Differentiation -Clinical and Laboratory Correlations R

Using intact human vessels we studied the phenotypic changes in medium sized arteries ex vivo and in vitro after exposure to Ca and PO 4 . Arteries were retrieved during insertion of PD catheters or at transplantation from 34 children: dialysis (n=20), CKD Stage IV (n=8) and compared with mesenteric vessels from 6 controls. Vessel rings were incubated with graded concentrations of Ca and PO 4 upto 21 days. Calcium and alkaline phosphate (ALK) were measured by cresolphtalein complexone and colorimetry. Immunohistochemistry for bone marker proteins, inhibitors of calcification and apoptosis were performed. Laboratory findings were related to patient's clinical and biochemical parameters, carotid intimamedia thickness (cIMT) and coronary calcification. Vessels from CKD or dialysis patients had increased baseline vessel wall Ca compared with controls (p=0.001). When exposed in vitro to Ca and/or PO 4 , dialysis vessels showed greater calcification than those from controls or CKD patients (p<0.0001). In the presence of elevated PO 4 even a small increase in Ca increased calcification (p<0.001). Calcification was associated with apoptosis (TUNEL +) and could be inhibited using apoptosis inhibitor ZVAD. ALK in CKD and dialysis vessels and along with upregulation of bone-markers suggests an osteogenic conversion of VSMCs

Using our unique in-vitro model, we have shown for the first time that vascular damage induced by elevated Ca-PO 4 as well as factors specific to dialysis primes vessels for rapid progression of medial calcification

Altered Expression of Major Renal Na + and K + Transporters C. Ruete 2 , P. Vallés 1,2 1 University of Cuyo, Department of Pathology

Turkey The effect of corticosteroid therapy on bone metabolism in nephrotic syndrome was examined. Sixty-nine patients with idiopathic nephrotic syndrome (age: 7.0±2,5 years) and 21 healthy controls (age: 6.4±3,5 years) were divided into 3 groups: Group 1: Patients who were on remission but still receiving steroid therapy, Group 2: Patients who were on remission and free of steroids within the last year and Group 3: Patients with active nephrotic syndrome and receiving steroid therapy. Serum total calcium, ionized calcium, phosphorus, alkaline phosphatase, magnesium, parathyroid hormone, 25(OH)D, serum cystatin C, urine protein, urine creatinine and urine cystatin C levels measured in all patients including the control group. In addition, lumbar spine bone mineral density Z scores were measured in the patient group

Objectives of study: We evaluated the clinical, laboratory and urinary tract echosonographic findings in patients with AH and RH. Methods: There was prospective clinical study, included 30 patients (mean age 6.6±2.5) with IH (normocalcemic, normophosphatemic, with 24 hours urinary calcium excretion greater than 4 mg/kg/day)

All analyzed parameters (dysuria, positive family history of urolithiasis, microscopic hematuria, urinary tract microlithiasis) showed low sensitivity and specificity, and none of the parameters could be considered reliable in differentiating AH versus RH. Average value of UNa/Cr was greater in patients with RH

Conclusion: None of the analyzed clinical parameters, laboratory and echosonographic parameters except values of urinary excretion after calcium deprivated diet could be considered reliable in differentiating AH versus RH. Patients with RH have higher level of 24 hours urinary calcium excretion than patients with AH. Patients with RH have significantly greater excretion of urinary sodium compared with patients with AH

Idiopathic hypercalciuria (IH) is defined as hypercalciuria with no detectable cause. Low BMD with increased fracture rate and tendency to short stature has been reported in IH patients. We aimed to perform calcaneus QUS in children with IH and relate to U-Ca, body height and number of prevalent fractures (Fx). 11 children (8 girls, 3 boys; patient. Body height was recorded and QUS was measured on both heels with Cuba Clinical. The 24-h U-Caexcretion (U-Ca/24 h) was assessed and calculated in mmol/kg/24 h. Results were expressed as Z-scores ±SD. Czech anthropometric parameters from a 1991 survey and previously obtained QUS values of the healthy Czech pediatric population served as reference data. QUS results were also calculated as height adjusted values with the use of heightmatched standards. U-Ca/24 h was matched to healthy European paediatric population values

We found no correlations between Fx and BUA (either age-related orheight-adjusted) or Fx and VOS (age-related or height-adjusted). Neither were there any correlations between U-Ca and Fx, or U-Ca/24 hand BUA or VOS, respectively. In conclusion, children with IH had normal height, normal values of BUA and low VOS

40 (FC)

491 (P)

652 (P)

268 (MR)

23 (FC)

126 (FC)

194 (OP)

523 (P) Alpay H. 399 (P)

854 (P) Amann K. 37 (FC), 810 (P), 818 (P) Amanullah F. 521 (P)

169 (OP) Amaro A. 77 (OP)

164 (OP) Amore A. 48 (SY)

831 (P) Anarat A. 277 (FC)

131 (MR)

322 (P)

191 (OP)

213 (FC)

75 (OP)

345 (P)

391 (P) Bael A. 192 (OP)

308 (P), 543 (P), 600 (P)

32 (FC)

129 (FC)

658 (P) Balat A. 349 (P)

444 (P)

19 (FC) Bayazit AK. 372 (P)

906 (P)

708 (P), 709 (P), 710 (P)

338 (P)

356 (P)

671 (P)

805 (P) Bensman A. 162 (OP)

153 (SA), 384 (P)

425 (P)

118 (FC) Bereczki CS. 66 (OP)

214 (FC)

93 (OP), 285 (FC)

197 (OP)

12 (SY) Bi Yl. 484 (P)

23 (FC)

370 (P)

171 (OP)

841 (P) Biyikli N. 399 (P)

398 (P)

227 (FC) Bocanegra V. 224 (FC)

122 (FC)

352 (P)

Boh M. 134 (FC) Bökenkamp A. 92 (OP)

271 (FC)

22 (FC)

177 (OP)

65 (OP)

92 (OP)

Bourrier T. 425 (P) Bouts AH. 103 (OP), 117 (FC)

77 (OP)

903 (P) Bubic-Filipi Lj

368 (P)

168 (OP), 271 (FC)

78 (OP)

486 (P)

389 (P) Caropreso M. 95 (OP)

277 (FC), 371 (P)

40 (FC)

459 (P), 460 (P) Chartapisak W. 817 (P)

530 (P)

693 (P) Chaves A. 77 (OP)

394 (P) Chemodanova M. 911 (P)

559 (P) Chen J. 76 (OP)

724 (P)

488 (P)

539 (P)

654 (P)

160 (OP)

396 (P)

645 (P), 650 (P), 836 (P) Clermont MJ

737 (P)

211 (FC), 472 (P)

55 (SY) Codoceo A. 523 (P) Coelho G. 77 (OP)

49 (SY), 221 (FC)

48 (SY)

704 (P)

214 (FC)

211 (FC)

846 (P)

206 (FC)

456 (P) Coutinho S. 868 (P) Coviello D. 333 (P)

223 (FC) Craig J. 108 (OP), 556 (P) Cransberg K. 214 (FC)

765 (P)

425 (P) Cristino S. 672 (P)

39 (FC)

532 (P) Cross J. 86 (OP) Cruz MR

22 (FC)

534 (P)

117 (FC), 558 (P), 630 (P)

55 (SY) Deanfield J. 127 (FC)

845 (P) Decena-Galvez A. 601 (P)

124 (FC)

571 (P)

415 (P) Deguchtenaere A. 98 (OP)

859 (P)

679 (P)

303 (SA), 373 (P)

381 (P) Delucchi A. 633 (P)

821 (P)

338 (P)

439 (P)

485 (P)

653 (P)

284 (FC), 599 (P)

20 (FC) Dinda A. 756 (P)

325 (P)

695 (P)

607 (P) Dittrich K. 37 (FC)

28 (FC)

307 (P), 445 (P) Dötsch J. 37 (FC), 810 (P), 818 (P) Dragon-Durey MA

388 (P)

34 (FC)

576 (P)

25 (FC)

833 (P)

594 (P)

512 (P)

660 (P) Dursun I. 344 (P)

344 (P)

500 (P) Edefonti A. 380 (P)

374 (P) Eke F. 265 (FC), 718 (P)

322 (P)

220 (FC), 269 (FC), 333 (P), 403 (P)

32 (FC)

338 (P)

706 (P)

384 (P)

Evim M. 430 (P) F Faerch M. 378 (P) Fallahzadeh MH. 448 (P)

473 (P)

248 (SY) Feig D. 353 (P)

681 (P)

644 (P)

Fella A. 96 (OP) Feneberg R. 176 (OP)

77 (OP)

862 (P) Filler G. 25 (FC)

849 (P)

104 (OP) Fischbach M. 157 (OP)

SY) Fitoz S. 408 (P)

117 (FC)

798 (P)

470 (P) Fujita H. 75 (OP)

441 (P) Fujita T. 769 (P)

443 (P) Fukuhara D. 816 (P)

171 (OP)

843 (P)

803 (P)

171 (OP)

189 (OP) Garnier A. 365 (P)

762 (P)

155 (OP)

251 (SY) Geary-Joo C

21 (FC)

32 (FC)

177 (OP)

141 (SY)

32 (FC)

605 (P) Gross ML. 116 (FC)

610 (P)

331 (P)

136 (FC)

205 (FC)

533 (P)

821 (P) Guo W. 76 (OP)

746 (P)

70 (OP)

344 (P)

Haberal M. 537 (P)

42 (FC)

72 (OP), 128 (FC)

271 (FC), 538 (P)

285 (FC)

266 (FC), 747 (P)

266 (FC)

851 (P)

268 (MR)

344 (P)

470 (P)

183 (OP)

164 (OP) Hernández AM. 638 (P)

75 (OP)

183 (OP)

28 (FC)

190 (OP), 271 (FC)

814 (P) Hou JR. 315 (P)

334 (P)

168 (OP)

315 (P)

204 (FC)

29 (FC)

305 (P), 306 (P) Iharada A

186 (OP)

185 (OP)

677 (P)

267 (FC), 283 (FC) 618 (P)

664 (P)

49 (SY)

793 (P) Kathiravelu A. 25 (FC)

100 (OP)

154 (OP)

104 (OP), 115 (FC)

385 (P)

665 (P)

765 (P)

734 (P)

749 (P)

643 (P)

18 (MR)

334 (P)

69 (OP)

471 (P) Kondo Y. 29 (FC)

647 (P), 891 (P) Kosuljandic-Vukic D. 503 (P)

205 (FC) Kovalski Y. 645 (P)

190 (OP)

815 (P)

312 (P)

611 (P)

Kru èic D. 910 (P) Krylova-Olefirenko A. 825 (P)

616 (P)

582 (P)

746 (P)

260 (SY)

118 (FC)

340 (P)

544 (P) Kurayama R. 185 (OP)

599 (P)

266 (FC) Lalatta F. 177 (OP)

515 (P)

257 (SY), 354 (P)

160 (OP)

432 (P) Lau YW

77 (OP)

77 (OP)

559 (P) Llanas B. 71 (OP), 136 (FC), 859 (P) Llewellyn-Edwards A. 270 (FC)

284 (FC)

348 (P)

263 (FC) Luis-Yanes M

354 (P)

589 (P)

293 (SY) Maeda A. 566 (P) Maekawa K. 602 (P)

830 (P)

453 (P)

477 (P)

841 (P)

410 (P)

323 (P) Mak R. 49 (SY)

95 (OP)

171 (OP)

625 (P)

20 (FC), 26 (FC)

226 (FC)

457 (P)

254 (SY)

20 (FC)

893 (P)

638 (P)

578 (P) Medynska A. 421 (P)

350 (P) Mehls O. 128 (FC)

855 (P)

277 (FC), 426 (P)

74 (OP)

179 (OP)

174 (OP)

115 (FC), 758 (P)

420 (P)

23 (FC)

368 (P) Molnár-Varga M. 525 (P)

227 (FC)

279 (FC)

487 (P) Montini G. 209 (FC)

774 (P)

523 (P)

74 (OP)

587 (P)

569 (P) Morimoto T. 187 (OP)

364 (P)

71 (OP)

345 (P) Morita T. 563 (P)

392 (P) Mortazavi F. 309 (P)

283 (FC) Moscaritolo E. 502 (P)

728 (P) Mosig D. 493 (P)

191 (OP)

226 (FC)

498 (P) Moxey-Mims M. 221 (FC)

158 (OP)

521 (P) Mudun A. 652 (P)

116 (FC) Mughal MZ. 895 (P)

828 (P)

Müller T. 165 (OP) Müller V. 218 (FC), 244 (SY) Müller-Esterl W. 745 (P) Müller-Wiefel DE. 23 (FC)

49 (SY), 221 (FC)

174 (OP)

FC)

185 (OP)

31 (FC)

504 (P) Nghia H. 490 (P) Niaudet P. 113 (MR)

372 (P)

312 (P)

Nuzzi F. 95 (OP), 96 (OP), 541 (P) Nwobi O. 592 (P)

171 (OP)

77 (OP)

393 (P)

75 (OP)

338 (P)

257 (SY)

567 (P) Ostalska-Nowicka D. 522 (P)

621 (P) Otukesh H. 477 (P)

322 (P)

710 (P)

543 (P) Ozen A. 498 (P)

230 (SY), 308 (P)

380 (P)

876 (P) Paik KH. 643 (P)

853 (P) Pan'czyk-Tomaszewska M. 337 (P)

459 (P)

35 (FC) Paripovic D. 611 (P), 612 (P), 647 (P)

207 (FC) Pasqualini T. 194 (OP)

FC) Pastori A. 463 (P) Pászka D. 100 (OP)

95 (OP)

334 (P) Pereira A. 77 (OP)

129 (FC)

275 (FC), 574 (P)

576 (P)

FC)

110 (OP), 344 (P)

Raes A. 98 (OP), 99 (OP), 223 (FC)

218 (FC)

535 (P) Rigden S. 22 (FC)

209 (FC) Ring E. 346 (P) Rink N. 104 (OP)

74 (OP) Ristoska-Bojkovska N

271 (FC), 538 (P) Roszkowska-Blaim M. 337 (P)

576 (P)

894 (P) Ruffo GB. 914 (P) Ruhlmann A. 193 (OP) Ruiter J. 85 (OP) Rumeau R. 206 (FC) Rusai K. 215 (FC) Rusnak F. 608 (P) Rüther U. 381 (P) Rutjes N. 785 (P) Rybarova S. 772 (P) Rychlik I. 776 (P) Ryckewaert-DHalluin A

477 (P) Sabasiñska A. 401 (P)

684 (P) Sabolic-Avramovska V. 348 (P)

721 (P)

162 (OP) Safouh H. 499 (P) Saha A. 530 (P) Sahin H. 512 (P)

184 (OP) Saint-Cyr C. 805 (P) Saito A. 450 (P)

29 (FC) Sakalli H. 537 (P), 708 (P), 866 (P) Sakalli Ercoban H. 426 (P)

13 (SY)

868 (P) Salusky I. 129 (FC)

74 (OP)

717 (P), 720 (P) Sarkissian A. 316 (P)

805 (P)

217 (FC)

414 (P)

215 (FC)

154 (OP) Sayili A. 590 (P) Schäfer B. 691 (P)

32 (FC), 34 (FC), 42 (FC), 51 (SY), 116 (FC), 228 (FC), 271 (FC), 276 (FC)

215 (FC) Schmidt-Gayk H. 281 (MR)

Schmidts M. 549 (P) Schmitt CP. 116 (FC)

195 (OP)

549 (P)

272 (FC) Schneider-Maunoury S. 381 (P)

549 (P)

49 (SY), 221 (FC)

23 (FC)

180 (OP)

869 (P) Seeherunvong W. 40 (FC)

887 (P)

185 (OP)

468 (P) Semama D

76 (OP)

748 (P)

470 (P)

656 (P), 657 (P) Shin YH

382 (P)

564 (P)

22 (FC)

372 (P)

416 (P), 519 (P), 652 (P) Siwiñska A. 343 (P)

276 (FC)

154 (OP)

717 (P) Spasojevic B. 612 (P), 647 (P), 910 (P) Spasojevic-Dimitrijeva B

Stanic M. 386 (P), 891 (P), 910 (P) Stankovic A. 386 (P)

644 (P)

125 (MR)

41 (FC)

74 (OP)

18 (MR)

361 (P)

869 (P)

711 (P)

711 (P)

772 (P)

869 (P) Szteblich A. 188 (OP) T

32 (FC)

679 (P) Taha G. 499 (P)

532 (P) Taheri Derakhsh N. 436 (P)

602 (P)

814 (P)

31 (FC), 790 (P), 807 (P) Tan PH

654 (P)

654 (P)

31 (FC)

422 (P)

177 (OP)

536 (P)

524 (P)

882 (P) Tizard E. 270 (FC)

738 (P) Toenshoff B. 120 (FC)

432 (P) Tönshoff B. 42 (FC)

731 (P)

160 (OP)

218 (FC)

20 (FC)

171 (OP)

66 (OP)

652 (P)

154 (OP)

219 (FC) Urdaneta-Carruyo E. 551 (P), 872 (P) Urdaneta-Contreras A

277 (FC)

572 (P)

587 (P) Valverde S. 638 (P)

713 (P) Van Den Heuvel L. 118 (FC)

511 (P), 529 (P) Van't Hoff W. 297 (SY), 348 (P)

486 (P)

213 (FC), 700 (P)

11 (SY)

55 (SY)

272 (FC), 275 (FC)

738 (P), 791 (P), 792 (P) Waters A. 181 (OP)

38 (FC), 121 (FC), 273 (FC)

268 (MR)

72 (OP)

117 (FC)

129 (FC)

72 (OP)

227 (FC), 904 (P)

33 (FC) Wingen A. 168 (OP)

142 (SY)

219 (FC)

49 (SY), 221 (FC)

21 (FC), 693 (P)

264 (FC)

13 (SY)

473 (P)

135 (FC)

322 (P)

798 (P)

816 (P)

79 (OP), 784 (P)

29 (FC)

775 (P)

Yap HK. 31 (FC)

795 (P) Yata N. 497 (P)

174 (OP)

340 (P)

801 (P) Yilmaz A. 519 (P)

174 (OP)

67 (OP)

439 (P)

579 (P)

794 (P) Zhou JH

40 (FC)

165 (OP), 211 (FC), 233 (SY) Zingg-Schenk A

858 (P)

209 (FC) Zurowska A. 32 (FC)

161 (OP)

The IL6 (-174G/C) Polymorphism is Associated with Initial Peritoneal Transport Status in Children Commencing Chronic PD Acknowledge: this study was from Iran University of Medical Science.

Atypical Hemolytic Uremic Syndrome: an Unsolved Case of Complement Dysregulation 788 (P) 

Aim: We have shown that rats overexpressing IL-13 gene developed a MCN with proteinuria, hypoalbuminemia and hypercholesterolemia. This study aimed to determine the role of IL-13 on hypercholesterolemia in this model. Methods: Recombinant rat IL-13 gene in a mammalian expression vector was transfected into quadriceps of Wistar rats by in-vivo electroporation. Serum IL-13, albumin, cholesterol, creatinine and urine albumin were measured serially. After sacrifice on day 70, hepatic gene expression of HMG-CoA reductase (HMG-CoAR), ACAT2, cholesterol-7a-hydroxylase (Ch7aH), LDL-receptor (LDLR) and IL-13 receptor subunits were determined by RT-PCR. Results: Compared to control rats (n=17), IL-13-transfected rats (n=41) showed significant albuminuria (0.36±0.37 vs 3.45±0.89 mg/day, p<0.001), hypoalbuminemia and hypercholesterolemia (1.72±0.05 vs 3.39±0.34 mmol/L, p<0.001) at day 70. Serially, this rise in serum cholesterol preceded the increase in proteinuria and fall in serum albumin. Serum cholesterol correlated significantly with IL-13 levels (r=0.64, p<0.001). In 14 of the IL-13-transfected rats with serum cholesterol>3.10 mmol/L, hepatic gene expression (mean±SEM) was significantly upregulated compared to controls for HMG-CoAR (0.25±0.08 vs 0.54±0.05, p=0.02), ACAT2 (0.26±0.03 vs 0.43±0.04, p=0.009), Ch7aH (0.50±0.12 vs 1.08±0.10, p=0.004) LDLR (0.10±0.01 vs 0.15±0.02, p=0.02) and IL-13Ra2 (0.003±0.002 vs 0.080±0.015, p<0.001). Conclusion: The increased cholesterol synthesis in IL-13-induced MCN was associated with increased hepatic gene expression of HMG-CoAR and ACAT2, which are important enzymes for cholesterol synthesis. Associated increased hepatic gene expression of Ch7aH and LDLR involved in cholesterol metabolism could be a negative feedback response.

E. Bordador, F. Anacleto Philippine General Hospital, Pediatric Nephrology, Manila, Philippines General Objective: To formulate a clinical scoring system that will predict the presence of glomerular crescents in patients with severe nephritis. Specific Objectives: (1) to describe the profile of children with acute nephrotic-nephritic syndrome (2) to correlate clinical parameters with renal histopathology. Methods: This is a retrospective study. Twenty six charts from the Philippine General Hospital, admitted between January 2002 -March 2006 were retrieved. Included in the study were children with acute nephritic -nephritic syndrome who underwent kidney biopsy. Excluded were patients with small/contracted kidneys on renal ultrasound. Statistical tool used were Univariate analysis, Pearson's product moment method and Chi -square test. Results: Profile variables of the subjects were analyzed. Afterwhich, each clinical parameter was tested using univariate analysis, if significantly correlated with the renal biopsy result using Pearson's product moment method at critical value=0.388 at p<0.05. Out of 11 parameters, only 3 parameters were noted to be significant, these were serum creatinine, blood urea nitrogen and glomerular filtration rate. Further analysis was made by separately treating male from female population using a chi-square test with critical value X 2 (1,.05) =3.28. The test identified another three clinical features among female which were significantly associated with renal biopsy results, these were blood pressure, anemia and hematuria. From these significant parameters associated with renal biopsy results, a clinical scoring system was then conceptualized in order to identify patients With high probability of crescents on renal biopsy. Conclusion: CRESENT maybe use as an accurate screening tool to predict presence of glomerular crescent in patients with severe nephritis.

Heterogeneous Effect of ACEI Therapy in Children with Proteinuric Nephropathies B. Kranz, S. Diepenbruck, U. Vester, R. Buescher, A. Wingen, P. Hoyer University of Duisburg-Essen, Pediatric Nephrology, Essen, Germany Background: Chronic proteinuric nephropathies are at high risk of developing progressive renal insufficiency. The renin-angiotensin-aldosteron-system blockade is a well documented strategy to reduce proteinuria in adult patients. The efficacy and risks of renal-protective therapy with angiotensin-converting-enzymeinhibitors (ACEI) in children with proteinuric kidney diseases is of concern. Method: In this retrospective study the efficacy of ACEI as antiproteinuric therapy in children with chronic proteinuric nephropathies is evaluated. Patients: Sixty-three children (mean age 10.7±3.5 years) have been treated with ACEI for a mean of 2.7±2.3 years (range 0.1±10.6 years) because of proteinuria (HUS n=10, Alport syndrome n=22, PSH n=13, others n=18). Results: Proteinuria in all patients declined from a median of 1.5 g/d to 0.9 g/d after 2 years (p=0.01). There was a drop out of 5 patients because of end stage renal failure during the followup. One-third of patients showed a continuous reduction in proteinuria from 3.1 g/d to 0.4 g/d (median) within 3 years while a second third had a transientimprovement followed by a reincreasing proteinuria later. Patientswith HUS showed a good response (decrease of proteinuria from 2.8 g/d to 0.4 g/d) in contrast to patients with Alport Syndrome who developed increased proteinuria (0.8 g/d to 3.0 g/d) despite of ACEI and patients with PSH who had no change in proteinuria.Interpretation: It has to be discussed whether biological compensation mechanisms may bypass the ACE inhibition in single patients and whether the underlying illness may predict the efficacy of ACEI.Aims: To determine the clinicolaboratory renal manifestations; glomerular, extra-glomerular histopathologic lesions; renal tubular dysfunction (RTD) frequency, and outcome of a short-term renal follow-up in Nigerian children with systemic lupus erythematosus (SLE). Methods: A non-randomized prospective study of consecutive cases of childhood-onset SLE with nephropathy. Baseline/follow-up clinicolaboratory data were collected. Each patient was followedup for 12 months. Results: Seven of 11 children studied were girls (F:M, 1.75). Median age at diagnosis was 11.0 years. Median diagnosis time interval (1.9 years) and median time of renal disease onset (1.0 year) were similar. Hypertension, nephrotic syndrome, and acute renal failure occurred in 45.5%, 54.5% and 63.7% of the patients, respectively. The glomerular lesions were non-proliferative lupus nephritis (LN) in 9.0% (class II LN); focal (class III LN) and diffuse (class IV LN) proliferative LN (PLN) in 27.0% and 64.0%, respectively. Tubulointerstitial nephritis (TIN, 91.0%), and RTD (64.0%) were common. ARF (p=0.033) and RTD (p=0.015) were significantly associated with severe TIN. Complete renal remission rate at end-point was 71.4%. Relapse and renal survival rates were 14.3% and 86.0%, respectively. RTD was persistent in 43.0%. Conclusion: Renal function disorders, diffuse PLN, and extra-glomerular lesions were frequent. Significant association of ARF and RTD with severe TIN in this series suggests the need for early renal tubular function (RTF) assessment in our SLE patients. Deranged RTF may be marker of severe TIN in SLE warranting early confirmatory renal biopsy and aggressive interventional treatment.We report two cases of children with crescentic glomerulonephritis (GN) associated to isolated C3 deposits. Patient 1. A 9 year old girl was admitted for macroscopic hematuria, nephrotic range proteinuria (proteinuria/creatininuria=1000 mg/mmol) and renal failure (serum creatinine 600 μmol/L). ANCA and other antibodies were negative. C3, C4 and CH50 activity were normal but C3nef was detected. The patient was treated by prednisolone and cyclophosphamide pulses followed by oral corticotherapy. Renal function normalized, but proteinuria persisted (proteinuria/creatininuria=500 mg/mmol). A relapse occurred ten months later. Corticotherapy and cyclophosphamide pulses were reinitiated and were successful, followed by MMF maintenance therapy. Patient 2. A 4 year old girl was admitted after viral infection for macroscopic hematuria and fever. Proteinuria was of nephrotic range (proteinuria/creatininuria=708 mg/L). The search for autoimmunity was negative. C3nef was detected but C3, C4 and CH50 activity were normal. Serum creatinine increased to 369 μmol/L. After three pulses of prednisolone followed by oral prednisone, renal function normalized. Histological examination of the two renal biopsies revealed endo-and extracapillary GN with numerous granulocytes in the capillary lumen. Cellular crescents involved 90% of the glomeruli. Immunofluorescence demonstrated isolated C3 deposits in the mesangium and along the glomerular basement membrane (humps). C1q, IgG, IgA and IgM staining were negative.

Background: The risk of end stage renal disease (ESRD) is low in unilateral Wilms tumor, although patients with WAGR or associated genitourinary anomalies are at higher risk. ESRD is attributed mostly to hyperfiltration in the remnant kidney. Immune complex glomerulonephritis (ICG) has not been previously reported in Wilms tumor patients. Objectives: To report 2 cases of ICG in unilateral Wilms tumor. Methods: Retrospective chart review. Patient #1 a boy with cryptorchidism, diagnosed with unilateral Wilms tumor at 3 y of age. Patient #2 a girl with WAGR and unilateral Wilms tumor diagnosed at 2 y of age. Both had chemotherapy after tumor resection. Results: Patient #1: Within 2 mo of tumor resection, a proteinuria of 3.8 g/24 hrs and rising creatinine were noted. Renal biopsy was consistent with ICG. Within 5 mo of surgery the patient developed ESRD requiring chronic hemodialysis. Patient #2: Within 4 y of tumor resection, the patient developed progressive, asymptomatic proteinuria up to 2 g/24 hrs. The renal biopsy revealed changes typical for ICG. The patient was treated initially with enalapril and prednisone. Due to no response, mycophenolate mofetil (MMF) was added and prednisone was weaned. After 4 mo of therapy, her proteinuria improved to 0.5 g/24 hrs. her serum creatinine continued to be normal at 0.6 mg/dl, with calculated GFR of 113 ml/min/1.73 m 2 . Conclusions: This is the first report of ICG in patients with unilateral Wilms tumor with rapid progression to ESRD in the first patient, but successful response to MMF in the second patient. Despite low risk for progressive proteinuria in Wilms tumor patients, it is prudent to monitor these patients for proteinuria and perform a renal biopsy if proteinuria is progressive. MMF therapy may be attempted to decrease proteinuria and to delay the onset of ESRD.Aim of the study: to present our first results of rhGH treatment mainly in children on hemodialysis. Patients and methods: Sixteen children, aged 4.5-17.1 years (mean age 11.25±3.57) with height below -2.0 standard deviation score (SDS) for age or height velocity below -2.0 SDS for age, were selected to receive rhGH therapy at our Nephrology and Hemodialysis department. Most of them were on hemodialysis (14 children) with mean spent time 2.88±2.68 years (0-9 years) before an initiation of rhGH therapy. One half of patients were prepubertal (8 children) and second half were in early puberty (testicular volume between 4 and 8 ml for boys and breast development B2 or B3 in girls). All received 28-30 IU/ml per week by daily subcutaneous injection for 6 months to 3 years. The year before rhGH therapy served as a control period. Results: During the first year of treatment, mean height velocity in hemodialysis patients increased from 2.25 cm/year to 6.59 cm/year (p<0.0001) and in the second year was 5.25 cm/year (p=0.004). The mean height SDS in hemodialysis children did not improved significantly during the first year of rhGH treatment (from -3.01 SDS to -2.77 SDS, p=0.063). Neither weight, nor the body mass index varied compared with the pretreatment period. No change was observed in glucose, total proteins, albumins, cholesterol and triglycerides levels. The mean increment in bone age was 1.1 years. Pubertal status had no influence on response to rhGH. Conclusions: Therapy with rhGH improved height velocity in children with ESRD. No significant side effects were observed in 16 children during the 23.5 treatment years. Two patients developed secondary hyperparathyroidism but the relationship with rhGH remains uncertain. In our treatment group rhGH therapy was safe.

A. Waters 1 , A. Trautmann 2 , P. Zipfel 3 , E. Harvey 1 , Ch. Licht 1 1 Hospital for Sick Children, Department of Pediatric Nephrology, Toronto, Canada 2 University Children's Hospital, Department of Pediatric Nephrology, Heidelberg, Germany 3 

Atypical hemolytic uremic syndrome (aHUS) is characterized by the absence of a diarrheal prodrome, the tendency to relapse and a poor outcome. Functional and quantitative deficiency of complement regulatory proteins or inhibiting autoantibodies result in uncontrolled complement activation, which eventually causes aHUS. -We report a case of aHUS with complement dysregulation associated with a progressive refractory response to plasma infusions. Factor H and Factor H-related proteins (FHR) were quantified by ELISA and were further analyzed by Western blot. Complement activation was determined by measuring C3. Serial Hgb (g/dl), platelet, creatinine (mg/dl), LDH (U/l) were measured. Initial presentation was at 7 months of age with thrombocytopenia, hemolytic anemia and increased creatinine. aHUS was suspected as E Coli infection was ruled out. Disease remission followed several plasma exchanges. Monthly plasma infusion maintained remission. Therapy intervals exceeding 1 month promoted relapses. Nine years later, the relapse interval decreased and over the subsequent 3 years, thrombocytopenia persisted as plasma infusion requirements increased. A concomitant decline in renal function (creatinine 1.6 mg/dl) occurred with the development of persistent proteinuria and hypertension. At 13 years of age, she deteriorated acutely with hypocomplementemia and thrombopenia. Quantitative Factor H was normal. Autoantibodies to platelets and Factor H were negative. Intravenous immunoglobulin combined with oral steroids resulted in normalization of platelet count. Complement dysregulation is associated with aHUS. Hereditary defects can be treated with factor replacement therapy. Refractory responses may subsequently arise due to the development of autoantibodies against complement regulatory proteins. Complement dysregulation requires further analysis in our patient.

Objectives: angiopoietin-like 3 protein (ANGPTL3) is involved in lipid metabolism and angiogenesis. The present study was to examine ANGPTL3 expression in human kidneys with proteiuria, in adramycin rats (ADR), and in puromycin induced podocyte damage. Methods: immunohistochemistry was performed on kidney biopsies from children with MCD, MN, FSGS, TBMN. In ADR, ANGPTL3 expression was determined by quantitative real-time PCR in glomeruli and tubuli dissected from frozen section of kidneys with laser microdissection system. In MPC5, a conditionally immortalized mouse podocyte cell line in vitro, ANGPTL3, perlecan and agrin werer detected through real-time PCR with the induction of puromycin. Detachment assay was performed in podocytes tranfected by ANGPTL3-pcDNA3.1. Results: in human kidneys, co-labeling showed ANGPTL3 expressed in the cytosol of WT1 positive cells. Quantitative computerized analysis showed that ANGPTL3 in glomeruli in MCD and MN were significantly higher than that of TBMN, FSGS respectively (p<0.05). In ADR, ANGPTL3 in glomeruli increased significantly at 21 st or 28 th day (p<0.05) after adriamycin injection compared with control. And the expression of ANGPTL3 in glomeruli was correlated with 24 h urinary protein (r=0.81, p<0.05). In MPC5 both protein and mRNA expression of ANGPTL3 on podocytes were up-regulated with the induction of puromycin. In podocytes transfected by ANGPTL3-pcDNA3.1 the expression of perlecan or agrin increased significantly compared with control (p<0.05). The attachment ratio was shown 95.7%±3.3% 24 hs after puromycin treatment on podocytes transfected by ANGPTL3 compared with 38.6%±4.7% on normal podocytes, and 27.4%±3.5% on untransfected podocytes. Conclusions: ANGPTL3 is predominantly expressed in podocytes which could be involved in podocyte damage and the development of proteiuria. Purpose: we present 2 cases of a previously undescribed pattern of membranoproliferative glomerulonephritis, in children with neuroblastoma on chemotherapy. The pattern of injury shows unusual focal capillary loop proteinaceous deposits possibly related to toxic chemotherapeutic drugs. The resultant hypertension and renal impairment made bone marrow transplant a challenging prospect. Method: case series Results: Case 1: This boy with stage 4 neuroblastoma, developed severe renal impairment and hypertension during treatment. Thus there were difficulties in administration of chemotherapy and he required early surgery. At tumor resection a nephrectomy was necessary. He received an autologous stem cell transplant. He became unwell at transplant and required haemofiltration. He made a good renal recovery and did not relapse. Case 2: He was diagnosed at 2 months with stage 4S neuroblastoma. He completed treatment but later relapsed. During treatment his GFR reduced and he developed severe hypertension. This lead to restrictions in chemotherapy. Renal biopsy was carried out at tumor resection. At bone marrow transplant he was very unwell and required haemofiltration. He has chronic hypertension and low GFR. Light microscopy findings in both -global diffuse membranoproliferative pattern of injury -large numbers of proteinaceous resorption droplets -features of a protein deposition disease Electron Microscopy findings common to both -large number of differently sized protein droplets in the endothelial cells -no obvious immunecomplexes/deposits -protein deposition disease with a membranoproiferative pattern of injury Conclusion: both cases showed deposits in the kidneys which may be tumor protein in origin and the resultant glomerulonephritis, hypertension and renal impairment lead to challenges in transplant. The long term consequences are yet to be revealed. Methods: Establish the cultured glomerular mesangial cells of rat in vitro, 3~10 generations of cells were used in the experiment after identification. The experiment included five groups: Ctrl, LPS, high, middle and low dose FOS groups. GMC proliferation were detected by MTT. The changes of LN, FN and Col protein secretion were detected by the ELISA. The changes of LNbeta 2 mRNA expression were detected by semi-quantitative real-time PCR. Results: (1) FOS can inhibit the effect of proliferation induced by LPS. (2) Mesangial cells can secrete some ECM protein in normal culturing medium, ECM protein secreted by mesangial cells was significantly higher in LPS group than that in Ctrl group (p<0.01), while ECM protein was significantly lower in all FOS groups than that in LPS group (p<0.01). (3) LNbeta 2 mRNA expression was significantly higher in LPS group than that in Ctrl group, while that in FOS group was significantly lower than in LPS group. Conclusions: LPS can induce the increase of secretion of the ECM, including LN, FN, Col FOS can inhibit the secrection of ECM in GMC as dose-dependent manner at the mRNA and protein levels. The conclusion supplies the theoretical evidence for the renal protection of FOS.

H. Hong, W. Na, Y. Li, W. Qiang Guangzhou First Municipal People's Hospital, Department of Pediatrics, Guangzhou, People's Republic of China Objective: To observe the effects of Fosinopril (FOS), the new generation angiotensin-converting enzyme inhibitor (ACEI), on protein and mRNA expression of TGF-β1 of rat glomerular mesangial cell (GMC) induced by LPS; to demonstrate the preventive mechanism against glomerular sclerosis by applying FOS. Methods: Culture rat GMC in classic way. The cultured cell were divided into 3 groups, namely (1) Control group, (2) LPS group, (3) LPS+FOS group. Detect TGF-β1 concentration in GMC supernatant fluid by ELISA; estimate TGF-β1 mRNA expression by semiquantitative real-time RT PCR. Results: LPS group is obviously higher than control groups in TGF-β1 secretion and mRNA expression, while LPS+FOS group drops distinctively in TGF-β1 secretion and mRNA expression compared with LPS group. Conclusions: FOS has obvious inhibited on TGF-β1 expression of rat GMC both at protein level and mRNA level, which reveals that it might be an important mechanism by FOS on restraining the development of glomerulosclerosis.

R. Kahn 1 , N. Akbari 1 , J. Wieslander 2 , W. Müller-Esterl 3 , A. Christensson 4 , K. Westman 4 , T. Hellmark 4 , D. Karpman 1 1 Lund University, Pediatrics, Lund, Sweden 2 Wieslab AB, Lund, Sweden 3 Institute of Biochemistry II, Frankfurt, Germany 4 Lund University, Nephrology, Lund, Sweden Vasculitis is an inflammation with neutrophil influx in and around blood vessels. Patients may have elevated plasma levels of neutrophil-derived proteinase 3 and anti-neutrophil cytoplasmic antibodies (ANCA) directed to proteinase 3, suggested to be involved in the pathogenesis of disease. We have previously shown that the kallikrein-kinin system (KKS) is activated in vasculitis. In vivo the KKS is activated on endothelial cells and neutrophils when high-molecular-weight kininogen (HK) is cleaved by kallikrein thus liberating bradykinin. Bradykinin is a potent mediator of inflammation. In the present study we investigated if neutrophil-derived proteases, and proteinase 3 in particular, could induce activation of the KKS and bradykinin release. Purified neutrophils from ten vasculitis patients (3 adults, 7 children) and thirteen controls were treated with triton-X to induce lysis. Proteinase 3 was immunoadsorbed from the neutrophil extracts. Bradykinin and proteinase 3 levels were measured by ELISA. HK proteolysis was detected by immunoblotting. Proteinase 3 incubated with purified HK induced physiological breakdown of HK and bradykinin release. This was inhibited by preincubation of proteinase 3 with anti-proteinase 3. Triton-X treated neutrophil extracts from both patients and controls induced HK proteolysis and bradykinin release whereas the neutrophil extracts from which proteinase 3 had been immunoadsorbed did not. Levels of proteinase 3 in the neutrophil extracts from patients and controls did not differ. These findings suggest that neutrophil derived proteinase 3 can proteolyse HK in a physiological manner thus liberating bradykinin, thereby initiating kallikrein-independent activation of the KKS. Introduction: This is a prospective study to evaluate the safety and efficacy of Tacrolimus in 22 consecutive children with steroid-resistant nephrotic syndrome (SRNS). Methods: All of them were subjected to kidney biopsy. Tacrolimus was given in dose of 0.15-2.0 mg/kg/day in two divided doses to attain trought levels of 5.0-10.0 ng/l. These patients were followed-up every 2 weekly initially for the first month, followed by monthly visits. Urine spot protein creatinine estimation was done at each visit. Besides blood glucose, serum creatinine, urea, electrolytes, albumin, and complete blood count were done once a month. Results: The mean age of onset was 8.6±5.9 yrs. Of the 22 children, 9 had MCD, 11 had FSGS and another 2 had DMH on histopathology. Tacolimus had to be withdrawn in 3 children: Of the rest 19 children who received adequate therapy, complete remission was seen in 16 (76%) children, 2 (11%) attained partial remission and 1 was non responsive. The mean time to achieve remission was 59.9+45.8 days and the mean dose of TAC was 0.18+0.07mg/kg. The mean urine spot protein/creatinine ratios were significantly lower (0.64±1.09 vs 14.5±23, p=0.01) and mean serum albumin significantly greater (3.73±0.71 vs 2.45±0.52, p=0.001) as compared to those prior to TAC. Of the 16 children who attained complete remission, 2 patients are off steroids and TAC and in sustained remission, while the rest 14 are still on TAC therapy. Conclusions: This is the largest study so far on the safety and efficacy of Tacrolimus therapy in children with SRNS. We conclude that Tacrolimus is a useful therapeutic alternative in children with SRNS who are unresponsive to Cyclophosphamide and Cyclosporine.

Objectives: To describe HIV infected paediatric patients from our centre with pathology proven renal disease. Methods: Retrospective review of biopsy data base and case notes of patients with HIV referred with renal problems. Results: 14 patients were identified who had biopsy confirmed renal disease. The mean age of the patients was 5,7 yrs (range: 6 months to 16 years). Twelve of the patients were African and two were of mixed race. Renal pathology was divided into three groups: 1) HIV associated nephropathy (HIVAN): five patients. 2) Mesangioproliferative nephropathy: 4 patients 3) Other: acute pyelonephritis in 1, mesangial proliferation plus interstitial nephritis in 1, renal tuberculosis in 2, HIV immune complex disease (HIVICK) in one. Conclusion: There is a high degree of variability of renal pathology in children with HIV and renal disease which upholds the need accurate diagnosis when confronted with these patients. Background: Acute poststreptococcal glomerulonephritis (APSGN) is the most common glomerular disease of children in our country. It has not been studied well in this region yet. Here, we report our experience with PSGN in a tertiary referral center during a five-year period. Method: Hospital records of all 137 children who had been admitted from Mar. 2001 to Mar. 2006 to Nemazee hospital with diagnosis of acute glomerulonephritis (AGN) were reviewed. All demographic, clinical, paraclinical data and consumed medications were obtained. Results: Among 137 children diagnosed as AGN, 122 (89%) had APSGN. Other 15 (11%) children had MPGN (n=4), MESPGN (n=4), IgA nephropathy (n=2), lupus nephritis (n=2), RPGN (n=2), and FSGS (n=1). Mean age in children with APSGN was 8±3.5 (range, years. 117 children (96%) developed APSGN following a sore throat or upper respiratory infection while 5 (4%) cases developed after impetigo. Ninety-five (78%) patients developed APSGN during the cold seasons of the year. Periorbital edema was found in119 children (97.5%), hypertension in 92 (75%), gross hematuria in 88 (72%), oliguria in 45 (37%), generalized edema in 23(19%), azotemia (BUN>20) in 98 (80%), and nephrotic range proteinuria in 30 (24.5%). ASO titer was high in 103 (84%). Low C 3 was detected in 105 (86%) and low C 4 in 16 (13%). Dilutional anemia in 63 (51.5%), hyponatremia in 33 (27%), and hyperkalemia in 17 (14%) children among whom, 3 required hemodialysis. Regarding medications, 29 patients had received only furosemide, 73 cases took furosemide and nifidipine and for 10 patients furosemide+nifidipine+another antihypertensive medication was prescribed. Conclusion: Acute PSGN is the most common type of glomerulonephritis in this region. It follows sore throat in the majority of cases. It usually has an uneventful course.

Y. Guo, ZH. Wang, X. Liu West China Second University Hospital, Sichuan University, Department of Pediatrics, Chengdu, People's Republic of China Objective: We planned to explore the mechanism of glomerular basement membrane (GBM) damaged by RSV, through investigating the effects of LMWH on proteinuria and glomerular structure of RSV nephropathy. Methods: SD rats were inoculated with 6 10 6 PFU RSV and LMWH 400 IU/kg. Group A: RSV was given in the first 3 days, and LMWH was given for the following 11 days; Group B: the mixture of RSV and LMWH was given in the first 3 days, then LMWH was given for other 11 days; Group C: LMWH was continuously given throughout 14 days and on the 4 th -6 th day RSV was also given; Group RSV and the control were respectively inoculated by RSV and DMEM for 3 days. Renal histology, urinary protein excretion and serum parameters were observed. RSV RNA in renal and pulmonary tissue was determined by in situ hybridization. Results: There was no significant increase in urinary protein excretion of the LMWH-treated groups (A 7.4053±4.057, B 7.101±1.833, C 9.209±1.625, mg/24 h) compared with the control, but that of Group RSV (32.041±3.844 mg/24 h) gradually increased after RSV inoculation. There was just a decrease in albumin (15.060±1.335g/L) and an increase in urea nitrogen (12.9203±3.932μmol/L) of Group RSV only. No change of the glomeruli detected in all LMWH-treated groups, while congestion and swelling in glomeruli of Group RSV were observed significantly. Glomerular microstructures of the LMWH-treated groups were almost normal, while extensive foot process effacement was observed in Group RSV. RSV RNA signal expressed weaker in the LMWH-treated groups than in Group RSV. Conclusion: RSV damages HS on GBM by electrostatic interaction. LMWH, as the analog of HS, charged with anion, competes with HS to combine with RSV to keep GBM from being destroyed, and then reduce the proteinuria. S. Zhai, ZH. Wang West China Second University Hospital, Sichuan University, Department of Pediatrics, Chengdu, People's Republic of China Objective: The study is to explore the relevance among GAGs, Hpa and ELA in the Steroid Responsive Nephrotic Syndrome (SRNS). Methods: (1) 55 children with SRNS were selected, including the active (n=20), the convalescent (n=20), the remissive (n=15). 19 purpuric nephritis and 15 healthy children were served as the control.(2) Using the improved Whiteman process detected the urinary GAGs. ELA activities in plasma were determined by the amount of 4-nitroaniline released per unit time. Immunocytochemistry and image analysis method were used to detect the expression of Hpa of peripheral blood leukocyte. Results: 1. GAGs of the active were the highest (4.1051±1.1722) of all (P<0.001). In contrast with the healthy, the active and the convalescent (2.5666±0.6826, p<0.001) were significant difference, but the remissive no difference (1.6588±0.3103, p>0.05). 2. All of NS showed higher level of Hpa than the healthy (p<0.05). Comparing with the healthy, Hpa was significant difference both in the active (IOD 54786.2137±28714.0671, P<0.001) and in the convalescent (IOD 15708.6270±4036.2843, p<0.001),but no difference in the remissive (IOD 4181.0056±878.3909, p>0.05). By contrasting the active and the purpuric, their difference of Hpa was no statistic significance (p>0.05). 3. All of NS showed higher levers of ELA than the healthy (p<0.05). The healthy was strikingly different, contrasting with the active (77.4304±17.6366) and the convalescent (53.6803±7.4168, p<0.001), but no difference with the remissive (38.6552±9.1556, p>0.05). 4.There was a significant correlation among the urinary protein, urinary GAGs, Hpa and ELA with simple linear regression analysis. Conclusion: In the SRNS, proteinuria may be resulted by the spallation of Hpa and ELA for GAGs on GBM. (4), combination withhaematuria, hypertension and/or renal insufficiency (23), extrarenalsymptoms (6), and familial Mediterranean fever (FMF, 40) . Of the 85 non-nephrotic patients, 26 had extrarenal symptoms, 15 were nephritic,9 had rapidly progressive glomerulonephritis (GN), 6 renal failure and 29 isolated urinary abnormalities. Biopsy samples were evaluated by light microscopy in Yerevan and Zurich and by electron microscopy (except for amyloidosis) and immunohistochemistry (last 28) in Zurich. Results: The most common histological lesion was renal amyloidosis (25%), followed by focal segmental glomerulosclerosis (FSGS, 9%), lupus nephritis (8%),systemic vasculitis/HUS and minimal change disease (MC, 7.5% each),mesangioproliferative GN/IgA-nephropathy and membranous nephropathy(MN, 7% each), hereditary nephritis and membrano-proliferative GN typeI (6% each), acute postinfectious GN (APGN, 4%), and dense deposit disease (DDD, 3%). The miscellaneous group includes,apart from interstitial nephritis (1%), unclassified or inadequate biopsies and specimens with mostly sclerosed glomeruli(9%). The majority of patients with amyloidosis of FMF, FSGS/MC andMN were nephrotic, but 18% of patients with amyloidosis had non-nephrotic proteinuria. Conclusions: Several glomerular lesions were considerably more frequent than in other studies, particularly amyloidosis of FMF, MN and lupus nephritis, and to lesser extent membranoproliferative GN type 1 and DDD. APGN is underrepresented because less than 1% of all patients (>700) had a biopsy. This study would not have been possible without international collaboration.

Henoch-Schönlein Purpura in Children: an Epidemiological Study amongst Dutch Pediatricians on Incidence and Diagnostic Criteria J. Aalberse 1,2 , K. Dolman 2 , G. Ramnath 3 , R. Rodrigues Pereira 4 , J-C. Davin The aim of the present study on the incidence of Henoch-Schönlein purpura (HSP) in Dutch children is not only to give some insight in the epidemiology of HSP in the Netherlands but also to record the diagnostic criteria used by Dutch pediatricians and to evaluate the accuracy of the latter using the presence of IgA in the skin when biopsies are available. Methods: In 2004, all Dutch pediatricians received monthly a card asking to mention new diagnosed HSP. Pediatricians reporting one or more new patients with HSP were sent a list of questions concerning symptoms, blood and urine parameters, skin biopsy, diagnostic criteria and follow-up duration needed. Results: Two hundred and thirty-two patients from 0-18 of age (6.1/10 5 ) were reported as having started HSP in 2004. Twenty nine % presented with renal symptoms. In accordance with the classification criteria of the American Collegeof Rheumatology (ACR), eighty percent of pediatricians consider that isolated purpura (without hematological abnormalities) is sufficient to allow the diagnosis of HSP in children. From the 17 skin biopsies performed, only 9 (53%) presented with IgA deposits. The follow-up duration considered as necessary was longer in case of renal symptoms at presentation. However, 45% of patients without renal symptoms would be followed for more than one year. Conclusion: Considering the recent (2006) EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides, HSP should have been diagnosed in only 160 of the 179 patients of our study. The use of isolated non-thrombocytopenic purpura as only criterian to diagnose HSP in children might therefore lead to over diagnosis and unnecessary follow-up. Noteworthy, the EULAR/Pres criteria remain to be validated by a prospective study.

The clinical presentation and response to therapy of childhood PAN in Johannesburg, South Africa. Method: Retrospective record review of twelve children with a clinical diagnosis of PAN treated between 1993 and 2005. Results: There was unequal number of males and females; average age at presentation was 6.8±0.83-13.9 years, all were black children. Eight children had more than 3 ACR criteria and 11 sufficient clinical criteria (EULAR/PRES consensus criteria). Musculoskeletal and cardiac diseases were the commonest finding at presentation (75%), cutaneous, hypertension (58%), renal and gastrointestinal disease (50%), central nervous system disease (42%) and constitutional features (33%). Two children had bone involvementwith periosteal reactions on plain X-ray. Angiographic abnormalities were found in 8 (67%), and 9 (75%) had positive histology (skin/renal biopsies). Tuberculosis was diagnosed in 6 (50%), and 6 had positive streptococcal titers. All patients were ANA and hepatitis B negative, but there were five patients ANCA positive (2=P-ANCA, 2=C-ANCA, 1=both) (42%). The CRP was elevated in 8/12 (67%), ESR also in 8/12, while 58% had both elevated. All patients received oral glucocorticoids, 6 methylprednisolone (1-3 pulses-500 mg/m 2 ), 7 IVI cyclophosphamide (1-6 pulses, 500 mg/m 2 ), 10 oral azathioprine, and 1 required i. Conclusions: Children with PAN in Johannesburg present at a younger age with multi-organ disease. They require aggressive therapy with both glucocorticoids and cytotoxic therapy to ensure good outcomes. Objective of the study: In order to evaluate the predictive factors of chronic kidney disease (CKD), the records of 47 children with biopsy-proven mesangioproliferative nephrotic syndrome (MPNS) admitted between 1972 and 2005 were retrospectively reviewed. Methods: Renal survival was analyzed by the Kaplan-Meier method and Cox's regression model. Two multivariate models were developed: (1) from the onset of symptoms to the occurrence of CKD and (2) from the time of renal biopsy to CKD. The following data were obtained at admission an dat the time of renal biopsy: gender, race, age at the onset ofnephrotic syndrome symptoms, age at admission, blood pressure, laboratory data (serum creatinine, serum urea, glomerular filtration rate, 24-hr urinary protein excretion, hematuria). Patients were classified according to the response to the initial course of prednisone: (1) a complete response was defined as a proteinuria <0.3g/day; (2) a partial response was defined as urinary protein excretion of <1 g/day and >0.3g/day, and (3) no response was defined as urinary protein excretion of >1 g/day. Results: Median follow-up time was 8 years (IQ range, 3.9±13.7) and 12 patients (26%) progressed to CKD. At baseline, after adjustment 2 variables remained as independent predictors of CKD: creatinine >1.0 mg/dl (RR=3.8, CI 95%=1.01±11.3) and non-response to steroids (RR=10.7, CI 95%=2.2±51.2). At the time of renal biopsy, after adjustment 2 variables remained as independent predictors of CKD: age>7.5 yr (RR=3.8, CI 95%=1.0±14.3) and creatinine >1.2 mg/dl (RR=3.3, CI 95%=0.97±11.2). Conclusion: Serum renal function at baseline and initial response to prednisone were strong predictors of progression to CKD in our cohort of children with mesangioproliferative nephrotic syndrome. Methods: An illustrative case history of a boy with SLE and VHD in the absence of antiphospholipid antibodies was described. Results: A 14-year-old boy with a history of SLE for about five years was admitted to our hospital due to intermitted arthralgia, facial erythema, increased serum creatinine and oliguresis in October 2006. He had been treated irregularly with prednisone and immunosuppressants. However,the disease was not always controlled well. During thishospitalization, the problems of hypertension, renal failure and anemia had been resolved and maintained, but the problem of intolerance to increased circulation volume was obvious, and three times echocardiography (ECC) showed moderate to severe mitral valve insufficiency. Reviewed his history, suspected mitral leaflets vegetations was revealed by ECC four months after onset, he complained of chest pain, chest distress and breathholding several times without causes since eighteen months after onset and manifested with heart failure once, and ECC showed moderate to severe mitral valve regurgitation four months ago and twenty days ago respectively. Ruling out the possibility of infective endocarditis, rheumatic heart disease and congenital heart diseases, VHD were considered secondary to SLE. Since the VHD becomes hemodynamically significant, valve surgery is needed. Conclusions: VHD is generally asymptomatic and omitted easily, so routine cardiac evaluation of children with SLE using electrocardiography, echocardiography and chest X-ray is recommended to early detect and treat cardiac abnormalities, which may lead to better survival.

Objective: We have previously reported that Deleted in Esophageal Cancer 1 (DEC1), a potent tumour suppressor gene, was specifically upregulated in CD4+ cells of patients with relapse of MCNS, using differential display RT-PCR. This study aimed to further characterize the potential function of DEC1 in MCNS. Methods: Semi-quantitative RT-PCR was used to verify the DEC1 gene expression in children with relapse and remission of MCNS. Jurkat cells were transfected with plasmid containing DEC1 gene or vector alone. Gene expression was regulated by Tet-on/off system. The effect of DEC1 on Jurkat cell proliferation was assessed by 3 H-thymidine incorporation. Cell cycle analysis was performed following propidium iodide staining. Protein localization was determined by immunofluorescent staining with anti-DEC1 antibody. Results: We confirmed that DEC1 gene expression was significantly increased in 15 children with MCNS in relapse (0.93±0.17), as compared to remission (0.44±0.13, p<0.002), 10 normal controls (0.59±0.06, p<0.01), 7 patient controls with viral infections (0.58±0.03, p<0.03) and 7 nephrotic patients with other forms of glomerulonephritis (0.48±0.10, p<0.03). In DEC1-transfected Jurkat cells, cell proliferation was inhibited by 47.2%, compared with vector control. Cell cycle analysis indicated that DEC1 arrested Jurkat cell cycle progression by blocking its entry into the G2/M phase. Immunofluorescent staining with anti-DEC1 antibody suggested that DEC1 was a cytoplasmic protein, which was in agreement with PSORT. Conclusion: DEC1 gene expression was significantly upregulated in children with relapse of MCNS. Our results showed that DEC1 acts as a T-cell proliferation suppressor and arrests cell cycle progression, and thus may be important in mediating the number or function of CD4+ cells during relapse of MCNS.

Objective of study: The aim of the study was to assess plasma and urine concentrations of vascular endothelial growth factor (VEGF) in nephrotic syndrome children (NS) depending on the total dose of glucocorticoids (GC) and the percentage of lymphocytes with glucocorticoid receptor expression (CD3/GCR). Methods: We examined 51 children (2-15 years) , allocated to three groups: group I: 13 children with the first NS onset, group II: 13 children with NS relapse, group C: 25 healthy children. The NS patients were examined: A: before treatment and B: 4-5 weeks after prednisone administration at a dose of 60 mg/m 2 /24 h. Plasma and urinary VEGF levels were determined using the immunoenzymatic ELISA method. Flow cytometry was applied to assess CD3/GCR expression. Results: Higher plasma and urinary VEGF concentrations were noted in NS children before treatment (A), as compared to control subjects (C). Following prednisone therapy (B), VEGF level was reduced but it was still higher than in the control group. Positive correlation was observed between VEGF and protein in the urine (group I r=0.660, p<0.05, group II r=0.818, p<0.01) and a weak positive correlation between VEGF in plasma and urine (group I r=0.531, p<0.05, group II r=0.581, p<0.05). CD3/GCR expression was lower in group II. In both groups, the correlation between plasma VEGF and CD3/GCR was positive (p<0.05). Conclusions: 1. Plasma and urinary VEGF levels increase during nephrotic syndrome onset. 2. Glucocorticoid treatment reduces plasma and urinary VEGF levels in NS children. Objective of study: The aim of the work was to determine the expression of P-glycoprotein (P-gp) on peripherial lymphocytes (CD3) in children with steroid-dependent nephrotic syndrome (SDNS) during cyclosporine A (CyA) and ACE-inhibitor (ACE-I) treatment. Methods: The study group (I) consisted of 20 children with SDNS aged 5-18 years, with a subsequent proteinuria relapse at the time of prednisone dose reduction. All NS children were examined three times: A: at proteinuria relapse, before CyA treatment, B: after 3 months, C: after 12 months of CyA administration. Control group (II) consisted of 20 healthy children. CD3/P-gp was measured using a flow cytometry assay. Serum CyA level was assessed by means of the immunofluorescence method. Results: The expression of CD3/P-gp in NS relapse, prior to CyA+ACE-I administration was much higher (median 9.15%, range 1.50-13.50%) when compared to healthy controls (1.20% range 0.30-5.70%). The absolute number of CD3/P-gp in this examination was almost 5 times higher when compare to healthy controls (p<0.01). After 3 months of CyA+ACE-I therapy the expression of CD3/P-gp decreased dramatically and was similar to the controls. Similar results were obtained after 12-months of treatment. When analysing the correlation between CD3/P-gp and serum CyA concentration a strong negative correlation was found in both examinations. The correlation was stronger in group IB (during the treatment with higher CyA doses): (r=-0.624, p<0.01) than in IC (after reduction the CyA dose: (r=-0.464, p<0.01) Conclusions: The results of our studies indicate that CyA in SDNS inhibits the expression of P-gp. CyA is an alternative therapy that may lead to optimization of glucocorticoid doses, thus reducing the risk that goes along with treatment. Backround: Hemolytic Uremic syndrome is considered as the main cause of acute renal failure in childhood. It is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. The epidemiology of the disease varies between counties. Aim of the study: to describe demographic and epidemiologic aspects of HUS, presented in a 25 years period at the biggest Children's Hospital in the country. Material-Methods: 27 patients aged 11 days -12 years, mean age 4.8 years, (20 boys, 7 girls) were diagnosed with the syndrome. Of them 5, 18.5%, presented as D+ cases, 11 with preceeded respiratory system symptoms and 11 with no preceeded symptoms. Treatment consisted of fresh frozen plasma (FFP) and whole blood transfusions in all cases. Peritoneal dialysis was necessary in 7 cases, haemodialysis in 2, while plasmapheresis was performed in 3 cases. Three children, all boys, suffered from recurrent type of syndrome. A girl required treatment with peritoneal dialysis for 4 months followed by recovery of renal function. One-five years follow-up: One baby 8 months old died, 4 children received renal transplantation, in 5 renal function remained mildly reduced (GFR 50-80 ml/min/1.73 m 2 ) and 6 suffered of hypertension. The rest 11 recovered fully. Summary: HUS represents a rather minor public health problem with low mortality rate in Greece. Methods: Three children with pauci-immune LN were retrospectively reviewed. Results: The reported cases fulfilled the American Rheumatism Association criteria for SLE. At admission, all had a 1-month history of glomerulopathy without intensive therapy. Case 1 presented with nephrotic proteinuria, macroscopic hematuria and progressively deterioration of renal function. Laboratory data included a positive antineutrophil cytoplasmic antibodies (ANCA) on myeloperoxidase immunoassay. She was positive for lupus anticoagulant (LA) but negative for anti-cardiolipin (aCL) and anti-beta-2 glycoprotein I (β 2 GPI) antibody. Renal biopsy showed pauciimmune necrotizing and crescentic LN. Case 2 manifested with proteinuria, microhematuria and hypertension. ANCA was negative. Case 3 had nephrotic proteinuria, microhematuria and hypertension. The case had positive LA, aCL and anti-β 2 GPI antibody. ANCA was negative. The biopsy findings of both case 2 and case 3 indicated pauci-immune mesangial proliferative LN. Electronic microscopy revealed segmental and diffuse foot process effacement respectively. All three LN remitted following the treatment of steroid and immunosuppressive agents. Conclusions: These atypical LN were considered to be associated with the distinct pathogenesis, rather than immune complex-mediated glomerular injuries. We supposed the possibility of ANCAassociated necrotizing and crescentic glomerulonephritis for the first case. For the others, primary or secondary podocytes lesions might alter the glomerular permeability. The nephrotic syndrome is a clinical picture that characterized by proteinuria, hypoproteinemia, oedema and hyperlipidemia. Although the primer nephrotic syndrome is the most common type of nephrosis in children, it may also develop during the course of infections including Hepatitis B and C virus infections, whereas Hepatitis A virus infection related nephrotic sendrome is very rare in children. In this paper, we present a case of who had suspected diagnosis Hepatitis A virus infection related nephrotic syndrome. The boy at the age of 3 years was referred to our hospital due to vomiting, abdominal distension and oliguria. Physical examinations were revealed palpebral and tibial oedema, hepatomegaly, decreased breath sounds and mat percussion on right hemithorax. Icter were not detected. Laboratory examination were showed proteinuria, hyperlipidemia, hypoalbuminemia, high ALT and AST levels with normal levels of bilirubin, alkaline phosphatase, complement C3/C4, urea and creatinine. In viral serologic examinations, Hepatitis B and C related antibody were found negative, but anti-HAV IgM was found positive. Chest radiography and ultrasonography examination were revealed right pleural effusion and abdominal ultrasonography examination was revealed ascites. Based on these findings, we thought that the nephrotic syndrome could be developed due to anicteric Hepatitis A virus infection in our patient. Low dose steroid treatment was started (prednisolon 1 mg/kg/day, 1 month). Edema was improved, negative urine protein was seen, and liver functions were not deteriorated during this therapy in our patient. Hepatitis A virus may be cause of nephrotic syndrome by forming of immune-complexes. In conclusion, although Hepatitis A virus infection is rare cause of nephrotic syndrome in children, it should be investigated as a seconder casuse. Membranoproliferative glomerulonephritis (MPGN) is a rare, chronic glomerulonephritis, and its prognostic factors and outcome are not known very well in childhood. In this retrospective study, we reviewed the clinical, laboratory and histopathological features of children with primary MPGN. Thirty-three children (18 boys, 15 girls) presented at a mean age of 11.0 years (range 2-16 years). They were followed for a median of 44 months (range 12-92 months). The clinical presentation in children was nephritic-nephrotic syndrome in 15 children (45.5%), nephritic syndrome in 14 (42.4%) and nephrotic syndrome in 4 (12.1%). Nine patients had renal failure at presentation. At the end of study, 25 patients (75.8%) had complete remission and 8 patients had abnormal findings (4 proteinuria, 2 microscopic hematuria, 1 hypertension, 1 ESRD). All of patients were treated with steroid. Eight patients were given another immunosuppressant drug (cyclophosphamide 7, azathioprine 1) in addition to steroid therapy. The interval between appearance of symptoms and admission, durations of microscopic hematuria and proteinuria, and systolic blood pressure at presentation were higher in children with abnormal findings when compared with children with complete remission. There were no significant differences in clinical presentation type or histopathological features between children with abnormal findings and children with complete remission. Our results showed that delayed detection and treatment, uncontrolled hypertension and unresponsiveness to steroid in early period were poor prognosis predictors. We did not determine any correlation between histopathological findings and outcome. We need further investigations including larger patient population. Partial lipodystrophy (PL) is a rare condition of unknown etiology, with childhood onset. It is characterized by progressive loss of subcutaneous fat of face, neck, trunk and upper extremities together with C3 hypocomplementemia. Usually, patients do not have clinically evident renal disease or abnormalities until they have had the disease for 8 or more years. But, the case we reported here, firstly presented with membranoproliferative glomerulonephritis (MPGN), and during follow-up PL was observed. A six years old girl was presented with sore throat, vomiting and loss of appetite for the last fifteen days. Her development was normal and the child was asymptomatic till 6 years of age. The parents were relatives of the third degree. There was no history of similar cases in the family. The physical examination of the patient was normal. Urinalysis revealed hematuria and pyuria. Proteinuria was not present. Renal function tests were normal. Laboratory examination revealed low serum complement C3 but normal serum C4. The lipid profile was also normal. Patient was followed with the diagnosis of poststreptococcic glomerulonephritis. Because of persistent low complement C3 and nephrotic range proteinuria renal biopsy was performed at the 3 rd month of follow-up. Renal histology revealed MPGN consistent with type 2. C3 nephritic factor was negative. At the same time it was observed that the face took on a cadaverous look with prominent malar bones, chin and zygoma because of the loss of buccal fat. According to these findings, partial form of lipodistrophy, which is frequently associated with MPGN, was considered in the patient. During two years of follow-up she had two recurrences of nephrotic range proteinuria and she is now in remission with prednisolone therapy. As far as we know this is the first example of PL which is developed during follow-up of MPGN. Central nervous system abnormalities in children with acute post-streptococcal glomerulonephritis (APSGN) are rare and are considered to be secondary to acute severe hypertension, electrolyte imbalances and uraemia. Cerebral vasculitis associated with acute post-streptococcal glomerulonephritis has been rarely reported in pediatric literature. A 13-year-old girl with a severe headache, vomiting, edema and macroscopic heamaturia is presented. She had history of upper respiratory infection before two weeks. So, the patient was diagnosed as APSGN. On admission, she was normotensive and biocemically well balanced. Two hour later, she experienced a grand mal seizure. MRI examination of brain showed not only multiple areas of increased density in white and gray matter, and cerebellum but also subarachnoid bleeding, consistent with vasculitis. During follow-up, abducens nerve palsy was detected. Histopathological features on renal biopsy specimen, an elevated antistreptolysin level and fallen C3 complement level were compatible with APSGN. All clinical and laboratory abnormalities improved with steroid therapy (pulse and oral methylprednisolon). In conclusion, children with APSGN may present central nervous system abnormalities without hypertension, uraemia and electrolyte disturbances. Results: HSP was diagnosed in 105 patients, median age 6 years old. All had the skin manifestations, 49.5% abdominal pain and 41% arthritis. 45 patients developed HSP nephritis (42.9%), mean presentation time was 4.5 months after PHS diagnosis. Renal biopsy was performed in 14 patients, and the most common histopathological finding was HSP nephritis grade III A. Age of onset older than 10 years was statistically significant for nephritis development (Chi Square < 0.05). Chronic renal insufficiency incidence was 0.95%. Conclusions: The main complication of HSP is nephritis. Follow-up should include evaluation by a pediatric nephrologist. Age of onset older than 10 years is an important risk factor for HSP nephritis.

Objectives of Study: Acquired abnormalities of coagulation and fibrinolysis in nephrotic syndrome have been implicated in the pathogenesis of deep vein and arterial thrombosis. Resistance to activated Protein C due to amutation in the gene for factor V, the commonest inherited risk factor for venous thrombosis, could contribute to risk of both arterial and deep vein in patients with nephrotic syndrome. We report an arterial thrombosis in a young girl with idiopathic membranousglomerulonephritis (MGN) and factor V Leiden mutation. Case Report: A 14 year-old girl was admitted to our hospital with swelling of both legs and cyanosis of her toes. Her mother had history of abortion in the second trimester of gestation, and parents were second-degree relatives. Physical examination showed peripheral edema in both extremities and peripheral cyanosis in toes. Laboratory study showed the nephrotic range proteinuria. Serum albumin was 2.2 g/dL, and cholesterol was 380 mg/dL. Creatinine, electrolytes, prothrombin/partial-thromboplastin times, C 3 , C 4, fibrinogen, protein S, C, antithrombin III and homosistein levels were within normal limits. ANA, anti-dsDNA, P-ANCA, and C-ANCA, antiphospholipid IgG/IgM, anticardiolipin IgG/IgM were all negative. Genetic study showed the heterozygote mutation of factor V Leiden (FV/G1691A). In arteriography, there was complete occlusion on the posterior tibiaartery of left leg, occlusion of mid portion of right femoral artery and the posterior tibia artery of right leg. Renal biopsy findings werefelt to be compatible with MGN. Conclusions: We postulate that patients with concurrent nephrotic syndrome and factor V Leiden mutation may have an increased risk of thrombosis. Screening for factor V Leiden mutation may be indicated in patients with idiopathic nephrotic syndrome. Introduction: HUS (D+) is the 2nd cause of chronic renal failure (CRF) in children in Argentina. Proteinuria is the main predictor of progression to CRF. Patients with renal failure, when treated with restricted proteinin take show slower progression to end-stage of RCF. Proteinuria appeared in patients with HUS sequelae subject to an overload of protein intake. Objective: To evaluate the effect of a controlled protein intake on proteinuria in patients with renal disease due to HUS and normal renal function (>80 ml/min/1.73 m 2 ). Patients and Methods: Within a multicenter, randomized, double blind, controlled trial, carried out inorder to study the effect of iACE on the development of renal disease*, proteinuria before and after a controlled diet was measured in 102 patients with proteinuria due to HUS and normal renal function. Protein intake was indicated according to RDA for age. Protein intake was estimated with a questionnaire on former 72 hours, and with 24 hrs urea excretion. Proteinuria was measured in 24 hours urine collection at the beginning of the study and at 15, 30 and 60 days after onset of the study. Results: Median age at onset was 16.5 months (r: 7.0-85.0); mean of length of follow-up after HUS onset was 48.0 months (r: 4.0-155). In sixty five (63,7%) patients, proteinuria reduced to normal values; in the remaining 37 (36,3%) there was no change. Median of initial and final proteinuria in the 65 children whose proteinuria became normalised, was 9.83 mg/k/day (DS 3.71) and 2.44 (DS1.34) respectively <0.0005. Conclusion: Controlled protein diet (RDA) normalizes proteinuria in patients with significant proteinuria secondary to HUS and normal renalfunction. * A trial financed by Roemmers Laboratory, Argentina. Differential diagnosis of hematuria is the significant task of any nephrologist while most common reasons for hematuria demand histopathological diagnosis. IgA-nephropathy is the progressive glomerular disease which is known to be a common reason for hematuria. The diagnosis ofIgAnephropathy is often missed because of variability of clinical presentations, long-term asymptomatic course and therefore waiting tactics in prescribing renal biopsy. The aim of the study was to evaluate the incidence of IgA-nephropathy and to define its characteristic clinical and morphological features in children in Belarus. We present results of immunohistochemical staining for IgA mesangial deposition of 65 kidney biopsy preparations. The mean age of the patients enrolled in the study was 11,77±0,66 years. At the moment of biopsy patients clinically presented isolated hematuria (36%), hematuria with proteinuria (29%), nephrotic syndrom (12%), nephrotic syndrom with hematuria and hypertension (5%), isolated proteinuria (5%) and others in less than 2% each. IgA mesangial deposition was detected using immuno histochemical staining with polyclonal rabbit anti-human IgA. We found diffuse mesangial deposition of IgA in 18 patients (28% of all). Two of them had nonnephrotic isolated proteinuria, one nephrotic syndrom. Vast majority of patients were hematuric (either isolated or combined with proteinuria). IgA nephropathy incidence among hematuric patients was 38%. In histopathological examination we found mild segmental mesangial hypercellularity in 14 patients, mild to moderate global and segmental mesangial proliferation in 3 (in two of this patients we also found cellular and fibrous crescents in less than 30% glomeruli). One patient had focal-segmental glomerulosclerosis secondary to diffuse mesangial proliferative glomerulonephritis and clinically presented heavy proteinuria. We analyzed NPHS2 mutations in Chilean pediatric patients with SRNS due to FSGS, Diffuse Mesangial Sclerosis (DMS) and Minimal Change Disease (MCD). NPHS2 mutation analysis was performed in 31 patients (sporadic cases n=27, familial cases n=4). NPHS2 exons 5 and 7 were amplified by PCR and subjected to automatic sequencing or enzyme restriction analysis using ClaI (c.686G>A) and Hin6I (c.851C>T) respectively. Patients median age at disease onset was 24 months (range , 55% of which were male. Histological diagnosis were FSGS (n=26), DMS (n=2) and MCD (n=3). Ten of 31 patients (32.3%) had mutations in NPHS2 (9/26 FSGS, 0/2 DMS, 1/3 MCD). Eight of 10 patients bearing mutations were sporadic cases. Seven patients were compound heterozygous for R229Q and A284V. Patients with mutations were significantly older than those without mutations (median age 24 versus 84 months, p<0.01). Resistance to cyclosporin was observed in 6 of 7 cases with mutations and 11 of 18 cases without mutations (ns). We studied the frequency of R229Q and A284V in 60 healthy volunteers with similar ethnic background. Only one control individual was heterozygous for R229Q. No A284V mutation was detected. Our study demonstrated that NPHS2 mutations are a major cause of SRNS in Chilean pediatric patients. Since most of the SRNS patients bearing NPHS2 mutations were cyclosporin resistant, it is advisable to perform NPHS2 mutation screening before starting immunosuppressives. In this study we aimed to investigate the long-term prognosis of Henoch-Schönlein Nephritis (HSN) in childhood. Between 1991 and 2003, 156 patients with HSN were investigated retrospectively. There were 86 males and 70 females with a mean age of 9.6 years. They were graded according to the degree of renal involvement. Grade 1: isolated microscopic hematuria (n: 31); Grade 2: hematuria and mild proteinuria (n: 60); Grade 3: acute nephritic syndrome (n: 4); Grade 4: nephrotic syndrome/hematuria (n: 18); Grade 5: acute nephritic and nephrotic syndrome (n: 43). Renal biopsy was performed on 43 patients in Grade 4 and 5. Twenty patients had extensive crescent formation (>50%) on renal biopsy, and were given triple therapy [IV pulse methylprednisolone (MPZ) 30 mg/kg/d for 3 days, followed by oral prednisolone (OP), oral cyclophosphamide-2mg/kg/day for 2-3 months and dipyridamole]. The other 23 patients with <50% crescent formation were given MPZ followed by OP and dipyridamole. The patients in Grade 3 and 4 were given OP and dipyridamole. Grade 1 and 2 were not given any immunosupressive agent. During the follow-up period (mean 30±3.5; range 12-96 months), 23 patients in Grade 1, 38 patients in Grade 2, 2 patients in Grade 3, 8 patients in Grade 4 and 21 patients in Grade 5 showed complete remission (59%). Of the 5 patients with extensive fibrosis on renal biopsy, 2 had persistent nephropathy (1%) and 3 developed endstage renal failure (2%). The remaining 59 patients showed near-complete recovery with minimal urinary abnormalities (38%). In conclusion, although initial presentation of renal involvement determines the prognosis in HSN, intensive treatment with triple therapy appears to be effective in severe renal disease especially if started before the development of fibrotic changes in crescents and tubulointerstitial tissue. Aim: The bacterial infection in Nephrotic Syndrome (NS) is still the big problem and is one of the leading death causes in Ho Chi Minh City, Vietnam. We did this study with aims to overview this complication in children with NS. Methods: Our study population consisted of 132 children with nephrotic syndrome during one-year prospective cohort. Twenty seven out of 132 patients who developed severe bacterial infection including pneumonia, peritonitis, urinary tract infection, bacteremia or cellulitis were recorded. Results: From June 2004 to June 2005, there were 132 children with nephrotic syndrome recruited to the study. The severe bacterial infection stood at 20.5% (n=27). In 27 these children, 14 children were first NS, 13 children were relapsing NS. The percentages of pneumonia, urinary tract infection, cellular infection and peritonitis were 12.9% (n=17), 4.5% (n=6), 3% (n=4) and 2.3% (n=3), respectively. No patients with bacteremia were recorded. In 6 patients with UTI, E.Coli wasin 3 patients, proteus in 2 and enterococus in 1. NS children with UTI were asymptomatic. NS children with peritonitis had typically clinical manifestations of fever, abdominal pain, tenderness. One out of four patients with peritonitis cultured streptococcus pneumoniae inperitoneal fluid. Some factors associated with severe bacterial infection were increase in weight (12.7 vs 9.4%, p=0.02), very low serum albumin (10.3 vs 13 g/l; p=0.003), rise in serum a 2 globulin level (39.5% vs 34.6%; p=0.005) and hyperfibrinogenemia (5.8 vs 5.3 g/l; p=0.02). Conclusions: Bacterial infection has still been a common problem in children with NSin Ho Chi Minh Vietnam. It is important to investigate and manage this complication early to reduce mortality rate. Primary nephrotic syndrome (NS) is the most common glomerular disease in children which mainly responds to corticosteroids. However, >70% of children experience a relapse with recurrent episodes. The aim was investigation of outcome in NS patients, retrospectively. Clinical, histological data and treatment responses of children presenting with NS from 1996 to 2006 were reviewed. All patients were treated with steroid treatment firstly and classified as steroid sensitive NS (SSNS) and steroid resistant NS (SRNS) according to clinical or laboratory responses. There were 91 patients, 52 male and 39 female, had followed-up for 64.17±54.79 months. Age at onset ranged from 9-186 (median 34) months. Seven patients were admitted with hematuria and NS (5 MPGN, 2 MGN) that excluded from this study. 60 patients were treated by only classical steroid treatment. Thus, 60 (71.4%) patients were SSNS and classical steroid therapy was successful in this group.14 of all SSNS patients were evaluated with biopsy (6 FSGS, 8 DMP) because of frequently recurrent NS. In SRNS group (24 patients) with one cytotoxic agent, complete and stable remission was induced in 13 patients (6 in FSGS, 5 in MLH, 2 in DMP) while 6 patients (6 in FSGS) who responded to more than one cytotoxic agents had partial remission with symptomatic relief. Five children (5 in FSGS) were refractory to all cytotoxic therapies. Cyclophosphamide (CP) was used as the first cytotoxic agent in 18 patients and induced complete remission in 11 (61.1%). The patients who relapsed following CP and patients who failed to respond were treated with further cytotoxic therapies such as cyclosporine A (CS) or MMF. In 6 patients, CS was used as the first cytotoxic agent and induced remission in 2 patients (33.3%). Steroid must be the initial drug in childhood NS. CP could be used successfully as an immunosuppressive agent in SRNS patients.

Aim: Annexin V has a molecular weight of 32-35 kDa and has been reported to possess anticoagulant activity, inhibition of phospholipase A2, regulation of membrane transport, proliferation and signal transduction. It is reported that urinary annexin V concentration may be an indicator of apoptosis and acute renal injury related to the urinary protein level. The aim of this study is to define the role of urinary annexin V, serum annexin V concentrations as new prognostic tools and follow criteria in children with steroid sensitive and resistant NS. Methods: Annexin V concentrations were measured in serum and 24 hour urine samples in 23 steroid sensitive nephrotic syndrome (NS) patients in both relaps and remission periods (Group 1 and 2 respectively) and in 22 steroid-resistant NS (group 3) and sex and age matched 22 healthy controls (group 4). Total protein, albumin, cholesterol concentrations and 24 hour urinary excretion of protein and creatinine were measured in all groups. Results: In steroid resistant NS group (group 3), median of urinary annexin V/creatinine ratio was significantly higher than all the other groups (5048.8 ng/g creatinine (min-max: 1272.5-40498.4) vs 2839.5 ng/g creatinine (min-max: 1131.0-15835.4) in group 1 (P: 0.06); 2500.0 ng/g creatinine (min-max: 1424.2-11055.6) in group 2 (P: 0.028), and 2018.3 ng/g creatinine (min-max: 1225.9-6887.4) in group 4 (P: 0.028)). Serum Annexin V concentration was significantly higher in group 3 (median 16.6 ng/ml) than in group 4 (median 8.2). No significant correlation was found between urinary protein excretion and urinary annexin V/creatinine ratio. Conclusion: Remarkably increased urinary annexin V/creatinine ratio could be used as a determinant factor in children with steroid resistant NS, and it may be a prognostic factor in these children.

V. Baudouin 1 , F. Bernaudin 2 , A. Garnier 1 , T. Kwon 1 , M. Peuchmaur 3 , G. Deschenes 1 , C. Loirat 1 1 Hôpital Robert Debré-APHP, Service de Néphrologie Pédiatrique, Paris, France 2 CHIC, Service de Pédiatrie, Créteil, France 3 

cGVHD is the most common late complication of HSCT. Clinical manifestations mimic lupus disease but renal involvement is unusual. A 4 year-old boy underwent HSCT from an HLA-identical sibling donor for sickle cell disease. He received myeloablative therapy (cyclophosphamide, busulfan, antithymocyte globulin). Prophylaxis of acute GVH consisted in prednisone and MMF until month 4. Moderate skin and mucosa cGVH appeared at month 6 so that prednisone and MMF were restarted. At month 9 prednisone was stopped and MMF decreased to half dose. At 1 year, while clinical features of cGVH intensified, fortuitous diagnosis of NS was done. Glomerular filtration rate and blood pressure were normal. Biopsy showed membranous glomerulonephritis and mesangial hypercellularity. Immunofluorescence confirmed granular immune deposits of IgG and C3Treatment consisted in prednisone (1.5 mg/kg/d for 1 month, progressively tapered to 0.5 mg/kg/e.o.d at month 4) and cyclosporine (5 mg/kg/d, trough levels 40-50 ng/ml). Proteinuria decreased to <0.5g/l in 2 months. Cyclosporine was progressively stopped between month 6 and 12 without relapse of proteinuria. NS associated with cGVHD had been reported in about 60 patients (5 patients <18 yr-old). Retrospective studies estimate occurrence around 1% of patients with cGVHD. It was secondary to membranous glomerulonephritis in 67% of cases, minimal changes disease in 21%. Strengthening of immunosuppression led to complete remission in 90% of patients with minimal changes disease and 27% of those with membranous glomerulonephritis (60% partial remission). Usual treatment consisted in prednisone (87%) and cyclosporine (51%). This manifestation of cGVHD is probably underestimated and can occur at the same time or later than other clinical features. Early detection of proteinuria in patients with cGVHD is recommended to adapt immunosuppressive treatment.

Objectives: To see if cyclosporine A (CsA) is safe and effective in reducing proteinuria in children with the IgA nephropathy (IgAN) or the Henoch-Schoenlein purpura nephritis (HSPN). Methods: The biopsy proven 34 patients (19 with IgAN, 15 with HSPN) who showed increased proteinuria (>1+) for longer than 4 months were included. The blood level of CsA, serum chemistries, urine analysis and complete blood cell counts were carried out every other month along with the physical exams. Results: CsA was given at an amount of 4.41.0 mg/kg/day for 10.13.3 months in average. Complete remission of proteinuria in 27 (79.4%) and partial remission in 2 (5.9%) were achieved by CsA treatment. Five (14.7%) non-responders were discontinued for CsA treatment in the middle of the trial. The ration of urine protein to creatinine was initially 3.95.0 and reduced gradually with time to 0.81.6, 0.30.7, 0.50.9 at 4, 8, 12 months after CsA treatment, respectively. Twenty eight patients showed hypertrichosis, three experienced transient elevation of serum creatinine, and two complained difficulties in taking the medication due to severe nausea. For 28.3 months after completion of the CsA treatment, 9 patients redeveloped proteinuria and had to receive the 2 nd CsA trial. No clear difference was observed in the pharmacokinetic profiles of CsA attributable to the non-response or recurrence. follow-up renal biopsies were carried out in 11 patients after completion of the CsA therapy and no CsA toxicity was found. There was no alteration of linear growth pattern. Conclusions: This study has a limitation of lacking the control group but the CsA treatment is assumed to be very effective and a safe method to attain the remission of proteinuria in pediatric patients with the IgAN or HSPN.

J. Madrigal 1 , E. Fernandez 2 , P. Noguera 2 , P. Carranza 3 1 

The aim of this retrospective study was : 1) To correlate the histopathological diagnosis with steroid response,persistent hematuria, hypertension and or abnormal renal function tests (GFR) 2) To evaluate the response of the patients with SRNS and SDNS to the oral cytotoxic drugs , in a period of 10 consecutive years. 3) To correlate the response of this group of patients to the oral cytotoxic drugs with their histopathological diagnosis 4) To observe the incidence of FSGS in costarrican children during a period of 10 years. 5) Based on these observations, reevaluate the indications of the kidney biopsy in our patients .

We reviewed all the clinical records of patients with the diagnosis of NS and in whom a kidney biopsy have been done. Patients with incomplete data were excluded. Two consecutive reviews were made: the first included all patients diagnosed between January 1993 and December 1997 (Group A) and the second, between January 1998 and December 2002 (Group B). A total of 81 medical records were analyzed; 20 patients were excluded, and the remaining 61 were studied. Results: All patients had been referred for edema or new onset nephrotic syndrome before treatment had been initiated. In our patients the steroid response was also the most important factor to predict the histological diagnosis and the response to the treatment with cytotoxics. The presence of hematuria and abnormal serum creatinine at the time of diagnosis were a predictive factor for the steroid response but not for the histological diagnosis. Arterial hypertension achieved statistical significance only between MCNS and FSGS but it was useful as a predictive factor for the hystological. In our group of patients with SRNS treated with cytotoxics, 55.5% with MCNS responded, versus 37.8% of the patients with DMGN p<0,05.

A. Guersoni, V. Mello, V. Benini, S. Laranjo

Children with SRNS are exposed to prolonged and high doses of steroid therapy and other immunosupressants that can lead to a variety of serious side effects. These include statural growth impairment, obesity, osteoporosis, cataract, hypertricosis and psychological disturbances.We carried out a prospective single-center study to evaluate the efficacy of mycophenolate in 20 children with steroid-resistant disease, 7 female and 13 male, aged 11.5±4.2 years. Histological findings were: minimal change disease (MCD) in 8 children, focal segmental glomerulosclerosis (FSGS) in 11 and membranous nephropathy in one. All patients had been treated with at least one course of cyclophosphamide, metil-prednisolone in 15, while 13 had also been treated with cyclosporine before MMF. The initial dose of MMF was 600 mg/m 2 per day, together with a minimal reduction dose of corticosteroids associated with angiotensin II receptor blockers (ARBs) and sinvastatin.Three patients went into complete remission, 15 into partial remission and 2 showed no remission. Partial remission was described as loss of edema and improvement in symptoms, despite persistence of significant but improved proteinuria, that was classified either as moderate or low proteinuria according to the level. Side effects were: diarrhea (n=1), neutropenia (n=2), infectious disease (n=1). MMF is an important new therapeutic option when associated with angiotensin II receptor blockers (ARBs) and sinvastatin for SRNS with MCD or FSGS, providing improvement in edema and symptoms despite persistence of proteinuria, with no compromise of physical appearance or risk of nephrotoxicity. Background: Primary focal segmental glomerulosclerosis (FSGS) that is resistant to steroids and other immunosuppressive agents has a guarded long-term prognosis. Patients who fail to respond to current treatment may benefit from therapies that inhibit renal fibrosis and retard progressive loss of kidney function. Objective: The FONT study (Novel Therapies in resistant FSGS) is a Phase I clinical trial designed to test the safety, tolerability, and pharmacokinetics (PK) of novel agents that reduce renal fibrosis in patients with resistant FSGS. Methods: Patients, age 2-40 yr and eGFR >40 ml/min/1.73 m 2 , with resistant FSGS who fail treatment in the NIH supported trial evaluating cyclosporine vs. dexamethasone plus mycophenolate mofetil or who are screen failures due to prior exposure to these drugs are eligible. Patients are assigned to receive rosiglitazone 3 mg/m 2 per day po or adalimumab 24 mg/m 2 every other wk sc. The treatment phase is 16 wk and patients undergo an initial (wk 0) and steady state (wk 16) PK assessment. Results: 24 patients have been screened and 16 have been randomized 8 to each test therapy. 6 patients have completed rosiglitazone therapy and 2 have completed adalimumab. Four serious adverse events have occurred in patients receiving rosiglitazone, none related to the study drug. Fatigue (37%), gastrointestinal complaints (37%), and headache (25%) were the most common adverse events in patients given rosiglitazone. The outcomes in the adalimumab group have not been analyzed. Conclusion: These preliminary results indicate the feasibility of performing Phase I assessments of novel agents that can target renal fibrosis in patients with resistant FSGS. The findings will be used to design Phase II randomized clinical trials in this cohort of patients at high risk of progression to end stage renal disease. Supported by grant NIDDK R2170341.

Object: To study the effect of FTY720 on glomerulosclerosis and expression of cell cycle regulatory proteins in subtotal nephrectomized rats. Methods: 24 rat were divided into sham-operation group, glomerulosclerosis model group and FTY720 treated glomerulosclerosis group, 8 rats in each groups. The rats in later two groups were subjected to 5/6 nephrectomy. After operation, the treat group was fed with FTY720 for 12 weeks. The expression of collagen, fibronectin, and cyclinE, p21, p27 were determined by immunohistochemistry methods. Results: After treatment with FTY720, up began to decrease from 4w after operation, significantly lower than in model group (p<0.01). The model group showed higher level of Scr from 8w, which was much higher than in control group (p<0.05). In FTY720 treated group, Scr level were much lower than in model group. FTY720 could obviously inhibit the expressionof col-and FN in glomeruli and attenuate the extent of glomerulosclerosis. Moreover, FTY720 could upregulate glomerular expression of p21 and downregulate glomerular expression of p27 and cyclinE. The expression levels of p21 and cyclinE were significantly lower in treatment group than in model group (p<0.05), but still higher than in control group (p<0.05). p27 expression in glomeruli was stronger in treatment group than in model group (p<0.05), and lower than in normal group but without significant statistic difference. Conclusion: FTY720 can diminish urine protein excretion and prevent glomerulosclerosis in subtotal nephrectomized rats. This protective effect is presumed to be associated with its role in downregulation of cyclinE expression and upregulation of p27 expression in glomerular cells, and inhibition of extracellular matrix accumulation in glomeruli. The authors illustrate severe side effect of steroid therapy ulcerative gastroduodenitis-and rare complication (multiple cerebral thrombo-embolism) in the case of a 10 year old girl with steroid resistent nephrosis. In childhood occurence of thrombosis in steroid sensitive nephrosis syndrome is 1.5%, while it comes up to 3.8% in steroid resistant cases. On admittance she presented the classic symptoms of nephrotic syndrome. One month after the initiation of steroid therapy haematemesis, melaena occurred, and after appropriate therapy was cured. Due to the progression of the nephrotic syndrome, steroid shot and later immunesuppressive therapy was started. Eight weeks after onset she became unconscious for a shortwhile and had a transient episode of right hemiparesis. At the same time CT and MRI disclosed bilateral parieto occipital ischemic territorial vascluar lesions, with relative sparing of the cortical ribbbon. Following ICU observation her state rapidly improved and after a two week period she became free of symptoms. Renal biopsy disclosed the pattern of minimal change nephrosis with diffuse mesangial hypercellularity and a slight amount of IgM positivity. Immunological evaluation-with the capacitiy to reveal systemic immunological diseases remained negative. Having been put on an evidence based protocol the patient's present nephrological state was unremarkable, with proteinuria less then 1g/day. In the present work the authors discuss the factors predisposing to thrombo-embolism with special emphasis on the possible preventive measures and therapy. IgG autoantibodies to C1q (antiC1q) have been reported to play a pathogenic role in immunecomplex mediated diseases (SLE, APSGN, membranoproliferative GN, etc). The occurrence of antiC1q in adult patients with SLE has been shown to correlate with disease activity and some immunological parameters (hypocomplementemia, anti-dsDNA) and may be useful in the early diagnosis of lupus nephritis (LN) or even as a predictor of renal flares. The presence of antiC1q in children with APSGN was associated with more severe disease manifestations and a lack of spontaneous recovery. Associations between antiC1q, C4 and C3 complement levels and disease manifestations in 129 children with GN were investigated and compared with healthy controls. AntiC1q were measured by ELISA and C3 and C4 by immunoturbidimetry, respectively. 29 of 129 patients with GN were positive for antiC1q compared to 0/40 healthy controls. AntiC1q were associated with active LN and hypocomplementemia: 10/15 patients with SLE were found to be antiC1q-positive. Nine of these 10 had active renal disease at the time of blood sampling compared to 1/5 being antiC1q-negative. 7/10 antiC1q-positive patients had low C3 level and 4/10 had low C4 level. In children with APSGN, 13/38 were positive for antiC1q. AntiC1q positive patients had significantly higher proteinuria, more often hypertension and C3-hypocomplementemia. All 5 patients in which APSGN did not resolve spontaneously were antiC1q-positive. AntiC1q were associated with active nephritis and hypocomplementemia in patients with SLE. In children with APSGN antiC1q-positive patients have more severe disease and stronger C3-hypocomplementemia then those being antiC1q-negative.

M. Zahrane 1 , L. Fawaz 2 , L. Nesseim 3 1 Cairo University Hospital, Pediatric Nephrology, Cairo, Egypt 2 Cairo University Hospital, Pediatrics, Cairo, Egypt 3 Cairo University Hospital, Cell Pathology, Cairo, Egypt Objective of the study: Growth hormone (GH) and insulin-like growth factors are essential for normal growth and development. Chronic renal failure (CRF) results in major changes in the circulating growth hormone/insulin-like growth factor (IGF) system. Our aim is to study clinical and laboratory parameters of growth and osteodystrophy including IGF1 and IGFBP2 as part of the somatotropic hormone axis in Egyptian children suffering from CRF on conservative therapy. Methods: 62 Egyptian children (47 boys and 15 girls) with a mean age of 9.7y (0.47 to 21.12y) suffering from CRF on conservative therapy and 21 controls were included in the study. Ht, wt and TSF were measured and followed up for a period of 6 months. At the end of the follow-up period serum for IGF1 and IGFBP2, renal function, electrolytes, Ca, P and alkaline phosphatase and acid base balance were measured and an X-ray of the left hand and wrist was done to determine their bone age by Tanner and Whitehouse. Results: Our study shows that Children suffering from CRF in Egypt on conservative therapy have growth retardation with a mean ht of 3.7 SDS, a mean wt of -2.24 SDS. TSF mean was -1.3 SDS. On the average the patients had a delay of 2.95y (±2.0) in their bone age. Their height was retarded more than their bone age with a height age/bone age of 0.8 (±0.18). Alkaline phosphatase as a markers of renal osteodystrophy is significantly correlated to the height, height age, bone age and to the pH. The mean IGF1SDS (-0.6±1.8) did not differ from that of controls while the mean IGFBP2SDS (2.4±4.6) was significantly higher in patients with CRF than in controls. Height and weight were significantly correlated to IGF1 but not IGFBP2. There is a significant correlation between IGFBP2 level and the glomerular filtration rate. Conclusions: The imbalance between normal insulin-like growth factor-I (IGF-I) and markedly increased IGFBP2 plasma levels plays a pathogenic role for growth retardation in children with chronic renal failure. The lower the GFR the higher the IGFBP2 level. The latters inhibitory action may provide hope for improving growth in cases of CRF by reducing the level of IGFBP2 or displacing IGF1 from it.

S. Sultana 1 , H. Rahman 2 , M. Hossain 2 1 Bangladesh Medical College, Pediatric Department, Dhaka, Uttara, Bangladesh 2 Bangabandu Sheikh Mujib Medical University, Pediatric Nephrology, Dhaka, Bangladesh Objective: To find out the impact of different etiology of chronic renal failure on growth in children. Methods: This prospective study was carried out in the Department of Pediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from October 2001 to October 2003. Fifty children of both sexes under 15 years of age with clinical and biochemical evidence of chronic renal failure (CRF) with creatinine clearance (Ccr) of <75 ml/min/1.73 m 2 were included in the study. On the basis of underlying causes of CRF, the children were divided into congenital (n=30) and acquired (n=20) groups. All patient's height and weight were measured. Radiographs of hands, digits, ankle and knee joints, lumbar spine & skull were obtained to evaluate the presence of renal osteodystophy (ROD) and for assessment of bone age. Serum intact parathormone (iPTH) level was also assayed in all patients. Growth parameters and presence of radiographic and biochemical features were evaluated in two groups. Results: CRF children due to congenital anomalies had stunting and wasting in 23 (76.7%) and 20 (66.7%) cases respectively and the difference between two groups of CRF patients was highly significant (P<0.001). Alkaline phosphatase (467.70±218.55 U/L) and iPTH (91.43±33.42 pg/ml) were also significantly higher than acquired group (P<0.001 and P<0.05 respectively). Radiographic features of ROD were present in 15 (50%) cases in congenital group in comparison to 4 (20%) in acquired group and the growth zone lesion was the commonest type of ROD in congenital group (66.7%). Conclusion: All efforts should be made to diagnose the presence of CRF as early as possible, especially in infants and in children with early onset CRF who seem to lose growth potential.

Introduction: In patients with thalassemia major the most important cause of morbidity and mortality is organ failure due to iron deposits, desferioxamine toxicity and anemia. This study was designed to define renal abnormalities associated with thalassemia and to find early marker (markers) of renal dysfunction. Patients & Method: 39 thlassemic children (18 female and 21 male) with mean age of 11.8±2.3 yr. were studied. All of them were received desforioxamine. 22 age and sex matched healthy children were involved in the study. Blood and timed urine sample were obtained for hematologic and biochemical tests. The results were compared between case and control group. Results: Mean value of BUN, Serum Creatinine, Creatinine Clearance, Serum electrolytes, Urine osmolality, fractional excretion of sodium and potassium were not statistically different between two groups. Level of urinary NAG (N-acetyle-beta-d-glycosaminidase) was significantly higher in patients than in controls (P: 0.001). There was a positive relation between urinary NAG and duration of disease (P: 0.04). The was no statistically significant relation between urinary NAG and serum ferritin. Tubular function was not altered by hypertransfusion. Conclusion: Proximal tubular dysfunction is found in thalassemic patients. Measuring urinary NAG Can guide the physician to find the early tubular abnormality in patients without frank renal dysfunction. Severity of the abnormalities is correlated with the duration of disease. The present study aimed to investigate the effects of isolated MA and MA associated with mild renal function impairment on fracture healing in rats. MA was induced by chronic ingestion of 2% ammonium chloride solution as the unique source of liquid and renal dysfunction was produced by unilateral nephrectomy. Thirty male Holtzman rats (200-260g) were divided into six groups: control group (C,n=5) non-operated rats receiving tap water, acidotic group (AC,n=5) non-operated rats ingesting 2% ammonium chloride; sham water (S,n=5) sham-operated animals receiving tap water; sham acidotic (SAC,n=5) sham-operated rats ingesting 2% ammonium chloride; nephrectomy water (N,n=5) nephrectomized rats ingesting tap water; and nephrectomy acidotic (NAC,n=5) nephrectomized rats ingesting 2% ammonium chloride. After one week, blood samples were obtained to measure pH and gases, and a fracture of the right tibia was manually produced. Four weeks later, fracture healing was evaluated by radiological and histological parameters. Blood pH and gases, serum electrolytes and creatinine were also determined. Data were compared by ANOVA followed by Newman Keuls or Fisher's Exact test. Fracture healing in NAC, AC, SAC animals was significantly altered as compared to C group. There was an additive effect of metabolic acidosis and unilateral nephrectomy in fracture healing process as shown by the comparison of SAC and AC rats using radiological and histomorphometrical parameters. There was no difference between electrolytes and creatinine levels in all groups at the end of the experiment. This study showed a higher frequency of delayed fracture healing and nonunion in the presence of MA, which is worsened by unilateral nephrectomy. Our data indicated an important interaction between bone and kidney in acid base homeostasis. Introduction: Dent disease, an X-linked recessive tubulopathy, is historically characterized by lowmolecular weight proteinuria, hypercalciuria, nephrocalcinosis/lithiasis and slowly progressive renal failure. Most cases are caused by mutations in the CLCN5 gene (Dent disease 1, OMIM #300009), some patients with Dent like phenotype have defects in the Lowe syndrome gene OCRL1 (Dent disease 2, OMIM #300555). Patients: 10 male patients from 7 families with urinary findings resembling Dent disease are reported. In 7 patients, mutations in the CLCN5 gene were found, in 3 patients OCRL1 mutations. All children have increased values of urinary alpha-1-microglobuline, but also unselective glomerular proteinuria. 6/10 have mild hypercalciuria, 4/10 demonstrate mild renal insufficiency. Amost all patients have increased echogenicity of renal parenchyma, but mild medullary hyperechogenicity is found only in 2 of 10 patients. Metabolic acidosis or renal phosphate wasting is not found. Interestingly, 5 of 10 children have increased values of creatinine kinase of unknown origin, clinically asymptomatic and independant of CLCN5 or OCRL1 mutations. Conclusion: The phenotype and genotype of Dent disease is very heterogeneous. Diagnostic criteria of Dent disease and of Lowe syndrome should be discussed.

E. Sahpazova, D. Kuzmanovska, L. Spirevska, N. Ristoska Bojkovska Pediatric Clinic, Nephrology, Skopje, MacedoniaThe nutritional condition of 35 children (22 males and 13 females) mean age 8.18±4.04 (range 1-16 years) with moderate renal failure have been followed for three year. Glomerular filtration rate (GFR) was measured by creatinine clearance calculated with Schwartz formula and was ranged from 13.59 to 75 ml/min per 1.73 m 2 . The nutritional condition was determined by anthropometrics and nutritional measurements. The patients were divided in four groups depending of their protein intake, primary disease, ages and glomerular filtration rate. All patients were following an -ad libidum -diet. Nutritional intake was determined by minimum of two 3-day prospective dietary diaries. 46% of children received significantly lower protein intake. The mean protein intake (% of WHO recommendation) determined by dietaries of patients with -sub-optimal intake -was 94.79% vs. 175.45% in patients with -adequate protein intake -(P<0.05). All patients have a calorie intake of at least 80% of the WHO recommendations. The relative distribution of calories was 11.22% from proteins, 57.66% from carbohydrates and 31.12% from lipids. Nitrogen balance in 15 patients was positive and correlated most significantly with increasing energy intake (r=0.58). Average values for height, weight, triceps skin fold, mid-arm muscle circumference, and body mass index were within 2 SD of the mean of the normal population. The protein intake, primary disease and age of the children did not have any effect on growth and development. Only patients with more advanced renal disease showed small score for height and growth velocity. Key words: Chronic renal failure; Uremic children; Nutritional status; Nutritional intake;

U. Aslanova 1 , T. Morimoto 1 , E. Farajov 2 , N. Kumagai 1 , N. Sugawara 1 , A. Ohsaga 3 , Y. Maruyama 3 , S. Tsuchiya 1 , S. Takahashi 4 , Y. Kondo 2 1 Tohoku University, Pediatrics, Sendai, Japan 2 Tohoku University, Medical Informatics, Sendai, Japan 3 Tohoku University, Physiology, Sendai, Japan 4 Nihon University School of Medicine, Pediatrics, Tokyo, Japan The extracellular calcium-sensing receptor (CaSR) located in either luminal or basolateral cell membranes of various types of renal tubules including proximal tubules, Henle's loop and collecting ducts has been thought to play a fundamental role in electrolyte metabolism. To further identify the physiological roles of the CaSR, we examined the effects of Ca 2+ and calcimimetics neomycin (Neo), gentamicin and gadolinium chloride Gd 3+ on the intracellular pH (pHi) of in vitro microperfused mouse medullary thick ascending limb (mTAL) cells of Henle's loop, by loading the cells with fluorescent pH indicator 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein and measuring the ratio of fluorescence emission at 530 nm after exciting the dye at 490 and 440 nm. In a steady-state condition in Hepes-buffered solution, the pHi in the mTALs was 7.29±0.04 (n=9). A concentration of 200 micromol/l Neo in the basolateral side decreased the pHi after 1 min by -0.13±0.02 (n=34, p<0.0001). The other calcimimetics showed similar effects on pHi, whereas none of these calcimimetics in the lumen affected pHi. Na + removal or the inhibition of Na + and proton transport with amiloride, bumetanide, or bafilomycin did not eliminate the effect of Neo on pHi. On the other hand, Clremoval clearly eliminated the Neo-induced pHi decrease (-0.06±0.01 vs -0.00±0.05 in Clremoval, n=4, p<0.003). Thus, we have demonstrated for the first time that the CaSR is involved in the regulation of the pHi in the mTAL and requires Clto exert its effect. Background: Paediatric nephrologists are often consulted for atypical rickets of renal or non-renal origin. The comeback of vitamin D deficient (classical) rickets in Armenia and elsewhere is not only a public health problem but also a new diagnostic challenge for nephrologists. The aim is to analyse all paediatric patients seen in 2006 with bone deformities and suspected rickets at the Arabkir hospital in Yerevan. Patients and methods: Patients with bone deformities came spontaneously or were referred by one of us (GK). Routine serum chemistry was done in Yerevan. Further investigations, if needed, and urine chemistry were performed in Zurich. Patients with rickets due to renal insufficiency were excluded. Results: In 2006 we have seen 22 patients (12 males) with rachitic bone deformities aged 17-46 months (mean 32±9.4) at diagnosis. Of these, 8 patients had florid vitamin D deficient rickets and 9 had sequelae of rickets but were radiologically and biochemically cured. These 17 children with classical rickets had to be distinguished from 5 patients with other forms of rickets: X-linked hypophosphataemia (XLH; 2), vitamin D dependant rickets type1 (1), and renal Fanconi syndrome (2) due to Fanconi-Bickel syndrome and idiopathic. Conclusions: (i) The rising number of vitamin D deficient rickets is of concern and due to neglected prophylaxis, (ii) Children with classical rickets came late and were in the same age range as patients with atypical rickets, (iii) Hence, and because of the larger number of rachitic children, an increased awareness of nephrologists -including a full diagnostic work-up -is needed in order not to overlook rare forms of rickets, (iv) Polar vitamin D metabolites should not be used before the precise type of rickets is known.

B. Spasojevic-Dimitrijeva, M. Kostic, A. Peco-Antic, D. Kruscic, D. Paripovic, M. Stanic University Children's Hospital, Nephrology Department, Belgrade, Serbia 

T. Porowski 1 , W. Zoch-Zwierz 1 , J. Konstantynowicz 2 , K. Taranta-Janusz 1 1 Medical University of Bialystok, 1st Department of Pediatrics, Bialystok, Poland 2 Medical University of Bialystok, Department of Pediatrics and Auxology, Bialystok, Poland There are no published data on calcium oxalate (CaOx) crystallization and therewith associated kidney stone disease in children. The aim of this study was to determine Bonn Risk Index (BRI) in children with urolithiasis in relation to healthy age-and sex-matched controls and to assess possible associations between BRI values and the size of renal stones. Methods. In this cross-sectional study, we compared BRI in 142 Caucasian children and adolescents (76 girls, 66 boys) aged 3-18 years (median: 14.3) in whom kidney stones were newly diagnosed and 210 healthy age-and sex-matched controls (105 girls, 105 boys) without urolithiasis. Urinary ionized calcium [Ca + ] was measured using a selective electrode, while the onset of the spontaneous crystallization was determined using a photometer and titrating with 40 mmol/L ammonium oxalate (Ox 2 ). The calculation of BRI value was based on [Ca 2+ ] to (Ox 2 ) ratio. High resolution renal ultrasonography was done to estimate the size of renal stones. Results. Our results showed that BRI values in children with renal stones were greater compared with healthy children without stones. BRI was 15-fold greater, BRI/kg body weight -10-fold greater, BRI/per 1.73 m 2 b. s. -13-fold, whereas BRI/BMI was even 23-fold greater in cases with stones than in controls. No significant association was observed between BRI and the size of stones. Interpretation. Children with kidney stones demonstrate increased Bone Risk Index compared with healthy subjects without urolithiasis. An increased BRI during growth, although unrelated to renal stone size reflects the risk for crystallization of calcium oxalate and may suggest early metabolic disorders leading to urolithiasis. This simple method appears to be accurate and cost-effective, thus BRI may be widely used for discrimination between stone-formers and healthy children. M. Dixit, N. Dixit Florida Children's Hospital, Florida Children's Kidney Center, Orlando, United States Acute tubulo-interstitial nephritis (ATIN) is an important cause of acute renal failure resulting from a variety of insults including rare immune complex-mediated tubulo-interstitial injury. Drugs including non-steroidal anti-inflammatory drugs (NSAIDs) are far most frequent cause of ATIN, but overall as an entity it remains under-diagnosed as symptoms resolve spontaneously if the medication is stopped. We present a 14-year-old male who developed acute renal failure 2 weeks after aortic valve surgery. He was put on aspirin following surgery and took ibuprofen for fever for nearly a week prior to presentation. He then presented to the emergency department feeling quite ill and was found to have BUN of 147 mg/dL, creatinine of 15.3 mg/dL and serum potassium of 8.7 mEq/L. Dialysis therapy was immediately initiated. A kidney biopsy showed inflammatory infiltrate consistent with ATIN. However, very intense tubular basement membrane (TBM) granular deposits of polyclonal IgG and C3 were noted. He needed dialysis for nearly two weeks and was treated successfully with steroids. His renal recovery and disappearance proteinuria took almost a year. In conclusion, we present an unusual case of TBM immune complex-mediated ATIN due to NSAIDs with severe but reversible renal failure.

The Effect of Corticosteroid Therapy on Bone Metabolism in Nephrotic Syndrome Background: Nephropathic cystinosis is characterised by lysosomal cystine accumulation leading to generalized Fanconi syndrome. Defective tubular reabsorption of proteins, mainly by the multi ligand receptors megalin and cubilin, is considered to be the cause of proteinuria in cystinosis. Whether increased glomerular permeability contributes to proteinuria in cystinosis is investigated in this study by evaluating 1) urinary protein pattern in cystinotic patients and healthy controls 2) expression of megalin, cubilin and their ligands transferrin, albumin, a 1 -microglobulin (a 1 m) and b 2 -microglobulin (b 2 m) in renal tissue. Methods: Urine of cystinotic patients and controls (n=6), aged 1-16, were immunoblotted using antibodies against megalin, cubilin, transferrin, albumin, a 1 m and b 2 m. Additionally, urinary levels of IgG, albumin, a 1 m and creatinine were measured. Results are expressed as mg/mmol creatinine (median, range). Presence of proteins in semithin paraffin sections from cystinotic and control kidneys was evaluated using antibodies mentioned before. Results: Cystinotic patients had increased urinary excretion of , P 90 <10) and all tested ligands of megalin and cubilin. Immuno histochemistry showed comparable expression of megalin, cubilin and their ligands in convoluted proximal tubules (PT), while the ligands in straight PT were only present in cystinotic patients. Conclusion: A selective proteinuria with high molecular weight protein excretion such as IgG indicates increased permeability of glomerular filtration barrier in cystinosis already at an early age. The presence of the megalin and cubilin ligands in endocytic vesicles suggests functional endocytosis. However, the enhanced staining of the ligands in cystinotic straight PT may be a result of incomplete reabsorption in convoluted PT. Background: Dent's disease and Lowe syndrome are the most frequent X-linked tubulopathies. Dent's is characterized by LMW proteinuria, hypercalciuria and nephrocalcinosis. In ca. 60%, this phenotype results from mutations in the CLCN5-gene. Lowe syndrome (congenital cataract, mental retardation and generalized Fanconi syndrome) is due to mutations in the OCRL1 gene. Stunted growth is another typical finding in Lowe patients. Recently, in a subgroup of Dent patients OCRL1 gene mutations have been demonstrated (Dent-2 disease). Aim of the study: Comparison of the growth pattern of patients with CLCN5 and OCRL1 mutations. Patients: Boys with proven mutations in CLCN5 (N=25, mean age 13.8±9 yrs) were compared with those with Dent-2 disease (N=11, 9±4 yrs) and those with OCRL mutations and a Lowe phenotype (N=6,14.9±7.7 yrs). Comparison of z-scores for height, weightand BMI. Results: CLCN5 positive boys had a significantly higher height-SDS (-0.87±1.4) than OCRL1 positives (Dent-2: -2.18±1.1/Lowe: -3.46±1.0). There were no significant differences in BMI-SDS and weight-SDS. The difference between weight and height SDS as a parameter for obesity in these small-statured children was higher in Lowe than in classical Dent patients, with intermediate values being found in Dent-2. Discussion: Although the renal phenotype of Dent-2 patients is identical with classical Dent, the former are more stunted. Therefore, the abnormal growth pattern in Dent-2 patients cannot be ascribed to renal dysfunction. Taken together with other findings (elevated CK and LDH, mild mental retardation) our findings illustrate that Dent-2 is indeed a mild variant of classical Lowe syndrome.

Quantitative Ultrasonometry of the Calcaneus in Children with Idiopathic Hypercalciuria

Lesch-Nyhan syndrome is a very rare X-linked recessive disorder characterized by mental retardation, spasticity resembling cerebral palsy, choreoathetosis, self-mutilation and hyperuricemia. Self-mutilation behavior is a hallmark of the disease. Hyperuricemia leads to hyperuricuria and uric acid nephrolithiasis. We report on a 7-year-old boy with Lesch-Nyhan syndrome with no self-mutilation behavior who was erroneously diagnosed as having athetotic cerebral palsy. Besides, he had no renal stones, the only renal abnormality detected were hyperechoic renal medullary pyramids, sonographicaly indistinguishable from medullary nephrocalcinosis. Bone disease is frequently observed in children with homozygous beta-thalassemia (THAL). We have observed an increased prevalence of renal stones in these patients. In order to understand the cause of this predisposition to renal stone formation we investigated markers of bone metabolism in our THAL children. We studied 23 THAL children (age range 3-16 years; 8 females and 15 males) with no eviodence of renal stones. THAL was diagnosed with haemoglobin HPLC study and genetic typing. All received blood transfusion and iron chelants on a regular schedule. Serum levels of PTH, osteocalcin, telopeptide C-terminale (cross-laps) were determined with ECLIA technique; serum vitamin D (25OHD3) with ELISA technique. Serum calcium, phosphate, uric acid, bicarbonate, creatinine, alkalin phosphatase and sodium, calcium, oxalate, citrate and creatinine in 24 hours and fasting urine were determined with common methods. As controls we studied 30 children with comparable age. Serum PTH and vitamin D were increased in 28% of our patients, serum osteocalcin in 64% and telopeptide C-terminale (cross-laps) in 92%. Hypercalciuria was observed in 26%, hyperoxaluria in 16% hypocitraturia in 11%. Significant correlation were found between PTH and osteocalcin (p<0.01) Cau/Cru (p<0.05); osteocalcin and cross-laps (p<0.005) and Vit D and Cau/Cru (p<0.05). Bone disruption due to bone marrow expansion may produce an increase in vit D and PTH production with hypercalciuria producing renal stones. Losartan is an angiotensin II subtype 1 (AT1) receptor antagonist used for controlling blood pressure and urinary protein excretion in patients with hypertension and chronic renal disease.

There are a few reports about the clinical implications of AT-1 receptor antagonism that may interfere with the kidney's defense against an acid load and may thereby exacerbate metabolic acidosis in the literature. The suggested mechanism is that AT-1 blockade by losartan exacerbates acidosis by inducing a distal-tubular acidification defect.We observed metabolic acidosis and hyperkalemia in five patients (3 females/2 males, age ranged 5-17 years) whom were given losartan. During the second week of the therapy all patients revealed a metabolic acidosis with (pH; ranged 7,19 to 7,33 and HCO3; ranged 11,9 to 17 mmol/l) hiperkalemia (ranged 5,6 to 6,7 mg/dl). The etiologies of chronic renal disease in the patients were focal segmental glomerulosclerosis (FSGS) in one, lupus nephritis in one and three had undergone renal transplantation according to different etiologies. Glomerular filtration rate was higher than 60 ml/sec/1,73 m 2 in all patients. Immune suppressive regimen of renal transplanted patients was based on tacrolimus in two patients and on cyclosporine A in one. Both renal transplanted patients and other two patients with FSGS and lupus nephritis were all receiving steroid, enalapril and mycophenolate mophetil at the same time during the losartan therapy. Metabolic acidosis and hyperkalemia were recovered within a week following the exclution of the losartan. In conclusion, we think detailed and controlled studies are necessary to determine the pathogenesis of the metabolic acidosis due to losartan and patients must be followed up very closely for the adverse effects of metabolic acidosis and hyperkalemia during the treatment. Objectives of study: Bartter's syndrome is a rare renal tubular disorder characterized by hypokalemia and metabolic alkalosis. It is also known to be effectively treated with potassium supplement, potassium sparing diuretics and indometacin. We experienced two sibling cases whose problems were incompletely solved with above mentioned conventional treatment, but rather completely with adjunctive therapy of regular hemodialysis with dialysate of low bicarbonate concentration. Case 1: This male patient was diagnosed of Bartter's syndrome when he was 3 months old. He was treated with potassium supplement, aldactone and indometacin with marked improvement. But he still had some problems of retarded growth, severe headache and episodes of marked hypokalemia which needed repetitive admission. When he was 10 years old, we put him weekly hemodialysis with dialysate of low bicarbonate concentration (20 meq/L). With hemodialysis, he has been in good condition for 2 years with stable blood pH and serum potassium levels. Case 2: This female patient, the elder sister of case 1, was diagnosed of Bartter's syndrome at one year of age. With those therapy on conventional medications, she seemed to grow out of failure to thrive, but needed repeated admissions due to episodes of dehydration and hypokalemia. After start of weekly hemodialysis with low bicarbonate dialysate, for one year she has been on good control of blood pH and serum potasium level, and was never admitted with those episodes. Conclusion: Regular hemodiaysis with dialysate of low bicarbonate concentration can be considered as effective adjunctive therapy in intractable Bartter's syndrome.

A. Deguchtenaere, A. Raes, J. Dehoorne, C. Vande Walle, R. Mauel, J. Vande Walle University Hospital Gent, Pediatric Uro-Nephrologic Center, Gent, BelgiumMonosymptomatic enuresis nocturna (MNE) may be associated with nocturnal polyuria (NP) and low urinary osmolality during the night. Besides vasopressin, recent studies have stressed the possible role of renal sodium-handling, hypercalciuria, prostaglandins and/or osmotic excretion.The aim: was to study circadian rhythm of GFR and diuresis in a highly selected group of children with persistant NP. Methods: population existed of 15 children with MNE and NP, age 9-14 y, 9 males. Controls n=25 children, 9-16 y with MNE, but no NP. (=B). Renal function during 24 h concentration-prophyle, with timed urine samples, and measurement of P and U for Na, K, osmol, creatinin. Calculation of GFR by creatinine, Uosmol, FEosmol, diuresis vol (ml/min), FENa, FECl, FEK, U K /U K +U Na %. Statistics: paired t-test p<0.05 between d and n, unpaired t-test, between the 2 groups. Conclusion: Children with nocturnal polyuria have not only lost their circadian rhythm of diuresis and sodium-excretion but also of GFR. Another observation for a reanl involvement in MNE. Sarcoidosis is a systemic disorder of unknown etiology, rare in children, characterized by the presence of noncaseating granuloma in affected organs. We report a 12-year-old boy of French african origin who presented with left hearing loss followed by bilateral deafness within 5 months. A history of bilateral uveitis was secondarily unveiled. Mild renal insufficiency (creatinine level 130 μmol/L ; clearance: 68 mmol/min) was diagnosed prior to cochlear implant surgery. A percutaneous renal biopsy evidenced a granulomatous interstitial nephritis with widespread interstitial fibrosis. Complementary explorations showed elevated lysozyme activity at 25 μg/L (normal <10) with elevated CD4/CD8 ratio in bronchoalveolar lavage specimen. Pulmonary function test was notable for mild diffusion impairment. Cerebral MRI demonstrated abnormal enhancement involving the periventricular white matter and the intracanalicular portions of both VIII cranial nerves. Cerebrospinal fluid showed abnormal hyperlymphocytosis (12 lymphocytes per mm3) while protein was normal. Three weeks after admission, bilateral uveitis recurred and was cured by local steroid therapy. Despite intensive treatment with intravenous prednisone 1 g/1,73 m 2 /j per day, 3 successive days per month associated with oral prednisone during 6 months, glomerular filtration rate did not improve.

In conclusion, sarcoidosis may apparently be revealed by acute bilateral deafness, and prompt diagnosis is needed to avoid permanent lesions. 1 GFR cystCin=91.869cystC -1.1227 , 2 FormGFR=38*height (cm)/S-creat (mmol/L). D difference between C inulin and tested method.

Conclusion: None of the tested methods seems to reveal hyperfiltration in type 1 diabetes patients as clearance of inulin. The best correlation was found to clearance of iohexol and second best GFR estimated by 100/cystatin C. Creatinine clearance overestimates and formula clearance underestimates GFR in diabetic patients without nephropathy. Objective: To study the effects and mechanism of FTY720 on the renal interstitial fibrosis in unilateral ureteral obstructic rats. Methods: Fouty-five males SD rats were randomly divided into sham-operated (SHAM), unilateral ureteral obstruction (UUO) and UUO treated with FTY720 (UUO+FTY720) group. 0.5 mg.kg -1 .d -1 of FTY720 or vehicle was administrated through daily gavage and begun from two days before the operation till being sacrificed. 24-hour urine protein, blood urea nitrogen and plasma creatinine were determined. The renal tubular interstitial fibrosis lesion and the expression of α-SMA,COL-I, CD3, ED1 were scored semi-quantitively.

Results: The amount of 24 hours urine protein was much lower than that in UUO group, (P<0.05). Serum creatinine in FTY720 treated group were significantly lower than those in UUO group (P<0.05). The scores of renal interstitial fibrosis were lower in FTY720 group than that in UUO group. α-SMA expression was limited to vessels in SHAM group, but extended to renal tubule and interstitium in UUO and FTY720 treated group, while relatively weaker expression was observed in FTY720 group than in UUO group. Some collagen expression was found in SHAM group, which was much enhanced in UUO group and mainly distributed in renal interstitium, the expression in FTY720 group was also increased compared to SHAM group, but much lower than that in UUO group. Obvious lymphocyte and macrophage infiltration were found in tubular interstitial area in UUO group but significantly less in FTY720 treated group (P<0.01).Conclusion: Novel immunomodulator FTY720 can obviously inhibit renal interstitial lymphocyte and macrophage infiltration, renal tubule cell transdifferentiation, and interstitial fibrosis, thus prevent renal disease progression. Background: The mesangial cell, especially as a fundationtal component in normal mature glomeruli, is essential to keep glomerular capillary lumen open and to maintain efficient ultrafiltration. Loss of mesangial cells due to pathologic conditions such as glomerulonephritis leads to impaired renal function. The exact developmental origin of mesangial cells is unknown. It has been established that mesenchymal stem cells, which are derived from bone marrow, have a potential to differentiate into different lineages in response to different environments. The purpose of the study is to examined the effect of platelet-derived growth factor (PDGF) in the differentiation of bone marrow-derived cells into mesangail cells.

Method: Isolated bone marrow cells were cultured in the medium containing collagen type I within 24 hours, and then transferred to collagen type I.-coated dishes. The cells attached to collagen type I. in the following 7 days were maintained in the differentiation medium containing 2% horse serum, 200 μmol/L, and 1 μmol/L of PDGF and all-trans retinoic acid. Results: After cultivation under the above condition, approximately 10% of cells expressed β actin and desmin, which highly resembled cultured mesangial cells in rat. The induced cultured cells changed into a wide range of shapes from spindle to stellate.

The results indicate that bone marrow-derived stem cells could differentiate into mesangial-like cells in vitro.