key: cord-1017927-7e4xfg6s authors: Mannemuddhu, Sudha; Pekkucuksen, Naile; Bush, Rachel; Johns, Felicia; Upadhyay, Kiran title: Transplant renal artery stenosis in a child with BK nephropathy date: 2019-12-09 journal: Pediatr Transplant DOI: 10.1111/petr.13629 sha: a952e2313ded3066ba37cbd82c099e4db4312e89 doc_id: 1017927 cord_uid: 7e4xfg6s TRAS and BK nephropathy are known complications of RT, but the association between both has not been reported. A 2‐year‐old girl underwent a deceased donor renal transplant from a 20‐year‐old donor, along with bilateral native nephrectomies. She had a DGF due to a renal artery thrombus and required thrombectomy with re‐anastomosis. Heparin and aspirin were used. Immunosuppressive agents included thymoglobulin, steroid, tacrolimus, and MMF. CMV and EBV DNA PCRs were negative, but she developed BK viremia at 2 months with stable allograft function. Immunosuppression was reduced, and leflunomide was initiated. Blood pressures were well controlled on low‐dose amlodipine. Five months after RT, she presented with hypertensive emergency, following a respiratory infection, and required dialysis for oliguric acute kidney injury. Allograft biopsy showed evidence of BK nephropathy. Immunosuppression was further minimized. Doppler renal US and renal artery duplex studies were both suggestive of TRAS. Angiogram showed severe proximal anastomotic TRAS (>95% occlusion). PTA with stenting was done with immediate improvement in the blood flow and reduction in the pressure gradient. BPs and renal function normalized. Ten months post‐RT, she remains normotensive with stable renal function and resolution of BK viremia. Although ureteral stenosis and nephropathy are known to occur with BK infection, TRAS is an interesting association and possibly suggest the tropism of BK virus to the vascular endothelial cells. Timely recognition and management of both is important to prevent uncontrolled hypertension and allograft dysfunction. Stenosis of the transplant renal artery is a well-known early complication of RT. 1 Early diagnosis and management is necessary to prevent allograft dysfunction and severe multi-system complications arising from severe hypertension. Post-RT surveillance of BK virus is commonly done at most transplant centers. BK viremia similarly is more common in the early post-RT period due to intense immunosuppression. 2 Untreated, BK viremia can progress to BKVAN, leading to transplant dysfunction. 3 Although CMV infection is known to occur in association with TRAS, 4 a concomitant BK viremia and TRAS has not been described. Here, we describe a 2-year-old girl who presented with such an association. A 2-year-old Caucasian girl had ESRD secondary to hypoxic-ischemic injury at birth. She required temporary RRT in the form of PD from 2 weeks until 4 months of age. PD was discontinued at 4 months of age due to recurrent fungal peritonitis. She was able to maintain stable electrolytes with good urine output while off PD. At 2 years of age, she received a deceased donor kidney transplant from an adult donor. Donor kidney was 10 cm in length with a single renal artery and vein. KDPI was 33%. Her height was 80 cm (5th centile), and weight was 12 kg (50th centile) at the time of transplant. It was a five antigen mismatched kidney. Pretransplant hypercoagulable workup was negative. Allograft was placed intra-abdominally. The donor renal artery was anastomosed with the recipient's aorta and the donor renal vein with the recipient's IVC via end-to-side anastomosis, using # 6-0 prolene suture. Bilateral native nephrectomies (right kidney 4 cm and left kidney 4.5 cm in length) were performed at the time of transplant to prevent dehydration episodes post-RT as she was polyuric prior to transplant, and also, it was thought that the 10-cm donor kidney would be little difficult to fit in this small patient. Intra-operative event was otherwise unremarkable. No peri-operative heparin was administered. Abdominal fascia was closed with # 2-0 PDS, and skin was closed with monocryl subcuticular suture. CIT was 8 hours and 38 minutes, and WIT was 49 minutes. There was an EBV and CMV mismatch (donor positive and recipient negative). She had an excision of her left parathyroid nodule 2 days prior to the transplant. A non-contrast MRI of neck done for persistent hypercalcemia and phosphaturia with normophosphatemia, suppressed serum intact PTH, elevated PTHrp (50-60 pg/mL), and FGF 23, had shown a left parathyroid nodule. Histology of the excised tissue showed the presence of thymic tissue. Induction was done with thymoglobulin (total 4.5 mg/kg) and methylprednisolone. She had an excellent graft perfusion immediately after anastomosis with good urine output, but after an hour, she progressively became oligoanuric, and by 4 hours, she was anuric. Serum creatinine remained at pretransplant level (~2.5-3 mg/dL). Doppler US of renal transplant showed poor blood flow, leading to emergency abdominal re-exploration 6 hours post-RT. An early thrombus was found at the renal artery tip for which she underwent thrombectomy, while the kidney was kept cold at back bench. An end-toside re-anastomosis of renal artery with the right common iliac artery was performed using # 6-0 prolene suture. Later, her post-transplant course was complicated by multiple hospital admissions due to viral respiratory illness, UTI, and febrile neutropenia. These episodes were managed with appropriate antibiotics, reduced immunosuppression, G-CSF, and supportive measures. Aspirin was discontinued at 2 months due to development of spontaneous bruising. MMF was held at 2 months post-RT due to severe neutropenia and BK viremia; the latter started at 2 months and peaked at 260 000 copies/mL (ARUP laboratories; normal: <390 copies/mL; quantitative PCR, serum) at 3 months post-RT ( Figure 1 ). for which she underwent end-to-side re-anastomosis after thrombectomy and that could have added further insult to the artery. End-to-side anastomosis has been reported in some studies as a risk factor for TRAS but has not been consistently demonstrated. 25, 34 To the best of our knowledge, BK infection has not been shown to be a risk factor for TRAS but is possible given its effect on endothelial cells as outlined above. One of the drugs used in the treatment of BK infection, leflunomide, can cause cutaneous necrotizing vasculitis but its association with TRAS is unknown. 35 Endovascular intervention with PTA with or without a baremetal stent is usually the first-line therapy for TRAS. Increased risk of graft loss has been reported regardless of angioplasty or not, 25, 29 but another retrospective study by Geddes et al 36 found no increased risk of graft loss in patients with TRAS who were treated with angioplasty vs those who did not receive angioplasty. Surgical repair is reserved for cases in which angioplasty is unamenable or unsuccessful. 37 Our patient had an excellent outcome with PTA and stent placement alone. In our patient, there appears to be the development of clinically provided more definite answer but it was not obtained due to several potential risks of such procedure. Also, both hypertension and allograft dysfunction are multifactorial, and hence, we cannot attribute these post-RT complications due to TRAS and/or BK viremia only. Both TRAS and BKVAN are serious complications after RT. Early diagnosis of both is necessary for improved allograft survival. In this report, we postulate that BK infection could be a risk factor for TRAS given the association. Further studies are necessary to determine any possible causal relationship between these two entities. Hence, it may be worthwhile to look at evidence of TRAS by non-invasive studies such as Doppler transplant sonogram and/or duplex renal artery study and if suggestive, invasive study such as angiogram, in patients with BK viremia and hypertension. Histological evidence of BK virus particles in the stenotic tissue may be very useful as well. The authors have no conflict of interest to disclose. Sudha Mannemuddhu, Naile Pekkucuksen, Rachel Bush, and Felicia Johns: Collected data, drafted the initial manuscript, and reviewed and revised the manuscript; Kiran Upadhyay: Collected data, conceptualized the study, drafted the initial manuscript, and critically reviewed and revised the manuscript; all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Kiran Upadhyay https://orcid.org/0000-0002-8441-0220 Kidney Transplantation, 7th edn Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients Mohajel-Shoja M. 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