key: cord-0731307-081kbtsi
authors: Esezobor, Christopher I.; Alakaloko, Adebimpe E.; Admani, Bashir; Ellidir, Rashid; Nourse, Peter; McCulloch, Mignon I.
title: Paediatric Nephrology in Africa
date: 2021-10-25
journal: Curr Pediatr Rep
DOI: 10.1007/s40124-021-00256-7
sha: 4d2219884a44db34f7e2ae64b7854bb018e67a6f
doc_id: 731307
cord_uid: 081kbtsi

PURPOSE OF REVIEW: We highlight the unique facets of paediatric nephrology in Africa in terms of the spectrum of kidney diseases, available diagnostic and treatment modalities, kidney healthcare financing options, paediatric nephrology manpower and the contribution of geography and demographics. RECENT FINDINGS: Paediatric acute kidney injury in Africa is now commonly due to sepsis rather than gastroenteritis. Steroid-sensitive form of nephrotic syndrome is far more common than was two decades ago. SUMMARY: The hot arid climate in North Africa and the tropical climate in most of sub-Saharan Africa, and the high rate of consanguinity, sickle cell disease and HIV drive the spectrum of paediatric kidney diseases in the continent. Kidney diseases are often precipitated by infectious triggers associated with poor living conditions and little access to medical care thus resulting in late presentation and often end-stage kidney disease. Although accessibility to kidney care has improved in the continent due to training opportunities provided by international professional organisations, most children still face significant barriers to kidney care because they live in rural areas, governments spend the least on healthcare and the continent has the least density of healthcare practitioners and nephrology trainees.

Africa is the second largest continent defined by land mass after Asia. The continent comprises 54 countries conveniently divided into five regions, namely Northern Africa, Western Africa, Eastern Africa, Middle/Central Africa, and Southern Africa. Geographically, most of the continent lies below the Sahara Desert and experience a tropical or temperate climate. The countries north of the Saharan desert face a hot arid climate that promotes stone formation in the urinary tract. The tropical climate in most of the countries in sub-Saharan Africa (SSA) is conducive for bacterial infections, tuberculosis and vector-borne diseases such as malaria. The continent is home to 17% of the world's population of 7.8 billion people and it is the youngest continent with a median age of 19.7 years; 40% of the continent's population is under 14 years [1, 2, 3]. In contrast, the median age of the world is 30.9 years. About half of the population of the continent reside in rural areas which is characterised by a high burden of infectious diseases and limited access to social amenities and healthcare with traditional remedies often the first remedy for any illness.

Africa is the poorest continent with a GDP per capita that is one-sixth of the global average [2, 3] . Of the 20 countries in the world with the lowest GDP per capita, 18 are in Africa [3] . Only six African countries (South Africa, Namibia, Botswana, Gabon, Equatorial Guinea and Libya) are rated as upper middle-income countries and none as high-income country (HIC) by the World Bank [4] .

Its relatively young population, high fertility rate, unique climate, and high poverty rate act in concert to shape the practice of paediatric nephrology in the continent.

Acute kidney injury (AKI) and nephrotic syndrome are the most reported paediatric kidney diseases in Africa (Table 1) [5-7, 8•] . The dramatic presentations of nephrotic syndrome and severe acute kidney injury reduce the likelihood of missed diagnoses. In contrast, the prevalence of chronic kidney disease and congenital anomalies of the kidneys and urinary tract remains low due to the absence of screening or antenatal ultrasound investigation and thus often an underestimation. Apart from North Africa and the Republic of South Africa, genetic kidney diseases in children are infrequently reported in the continent due to cost and unavailability of the tests [9, 10] . In North Africa, consanguinity contributes to the high prevalence of diseases such as sickle cell anaemia, hyperoxaluria and nephronophthisis while the hot arid climate coupled with high consanguinity promotes a high burden of urolithiasis in children [5, 11] . In most parts of sub-Saharan Africa, the high burden of malaria is reflected in its frequent finding in children with AKI [12, 13••] . About 40% of the 409,000 deaths from malaria in 2019 occurred in three African countries, namely Nigeria, Democratic Republic of Congo and Tanzania [14 •] . Two recent studies that used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI documented that 45.5-59% of children with severe malaria in two African countries developed AKI [15, 16••] .

Although the spectrum of kidney diseases in children in the continent may be similar to those of children in other regions of the world, there are unique features that bear material impact on the course of kidney diseases in the continent. Acute kidney injury in Africa is frequently community-acquired and due to sepsis, malaria, perinatal asphyxia and, less commonly to, gastroenteritis due to unsafe water and sanitation [12, 13••, 17-20] . Acute kidney injury due to perinatal asphyxia is partly driven by the high out-of-facility delivery of newborns that is prevalent in the continent [21] . Late presentation to medical facilities colours the presentation and course of many diseases in Africa [22, 23] . It is not unusual for children with nephrotic syndrome to present to healthcare with fluid oozing out from the skin. In addition, there are many children with congenital anomalies of the kidneys and urinary tract (CAKUT), such as posterior urethral valve (PUV), who present for the first time after the age of five years or in adolescence with little residual kidney function [24•] . Not uncommonly, despite the increased availability of ultrasonography, many children with CAKUT are not diagnosed before birth [25, 26] . This underlines a need for manpower training but may also reflect the grim situation where about 35% of births in the continent occur outside health facilities [21] . In practice, the paediatric nephrologist in the continent is frequently caring for children with common kidney diseases who have the most severe forms with little residual kidney function.

Secondary causes of glomerular diseases are relatively more common than in high-income countries. The continent is home to the largest population of people living with HIV. As a result, HIV-related kidney diseases are frequently reported in both children and adults [27, 28•] . Furthermore, the high prevalence of sickle cell disease in the malariaendemic region of Africa (most of Western, Middle and Eastern Africa) drives the burden of secondary glomerular disease [27, 29] . Again, in contrast to HIC, childhood nephrotic syndrome in Africa was historically likely to be steroid resistant. However, two large recent studies among Black children in Côte d'Ivoire and Nigeria reported a steroid sensitivity rate more than 80% similar to rates observed in European and Asian children with nephrotic syndrome [30••, 31] . Furthermore, a recent systematic review documented increasing rates of steroid-sensitive form of childhood nephrotic syndrome compared with resistant form [32] . Acute glomerulonephritis due to streptococcal infection remains a commonly reported kidney disease in children in Africa (Table 1) , but more children with glomerular diseases due to systemic lupus erythematosus are increasingly being recognised [33, 34] . The absence of a comprehensive paediatric renal registry for the continent (there is an active renal registry in South Africa) means the true burden of end-stage kidney disease (ESKD) in children is largely unknown and infrequently reported. Hence, there are few reports of the burden of ESKD in children in Africa. The scant data available suggest that the prevalence of paediatric ESKD is much lower in Africa than in North America and Europe. A recent single-centre study in Nigeria put the incidence of ESKD among children < 15 years at 4 per million at risk population [22] . Overall, in contrast to CAKUT as the leading cause of ESKD in children in Europe and North America, glomerular diseases are the frequently reported causes of paediatric ESKD in the continent (see Table 2 ) [22, 35, 36] . It does appear that in regions of Africa where non-Black children predominate, CAKUT is the most common cause of chronic kidney disease (CKD) and the converse is the case in regions where Blacks predominate. For example, in Egypt and Cape Town, South Africa, CAKUT is the leading cause of CKD, whereas, in Nigeria, KwaZulu-Natal, South Africa, and among Blacks in Johannesburg, South Africa, glomerular diseases were the most frequent causes of CKD [22, [36] [37] [38] [39] .

Availability of diagnostic and treatment modalities for kidney diseases in Africa is among the poorest in the world. The Global Kidney Health Atlas 2019, which detailed the 2018 survey of the ISN, documented that only 4 and 10% of patients with ESKD in low-income countries (LIC) and low middle-income countries (LMIC), respectively, received kidney replacement therapy compared with 60% in Western Europe [40••] . Furthermore, most of the countries with the least chronic haemodialysis (HD) and peritoneal dialysis (PD) centre densities are in Africa. In most countries in Africa, the survey estimated the chronic HD centre density at < 1.2 per million population (pmp). In Chad and Mozambique, for example, the density was 0.1 pmp. In addition, chronic PD was only available in 15 of the 42 African countries surveyed. In the continent, access of children to kidney care lags those for adults and is frequently inferior to adult services. The survey confirmed large disparities in ESKD care and access to KRT between children and adults within the same country. The disparity is more marked in LIC and LMIC to which about 90% of the countries in Africa belong. In LIC, the survey respondents reported disparity in ESKD care and KRT access in 61% and 57% of the countries, respectively, compared to 19% and 9%, respectively, in HIC. Some of the disparities are evident in the non-availability of size-compatible consumables for urodynamic investigations, catheters for haemodialysis and peritoneal dialysis and blood lines for haemodialysis [41] . Not infrequently, adult-sized 44, 45] . The median incidence of kidney transplantation in the continent is estimated at 4.6 pmp compared with the global median of 14 [46• ]. African countries with advanced KTx services, namely Republic of South Africa and the countries in North Africa, provide KTx for all age categories of children. However, in the other countries, only older children have such access. For example, a recent study in Nigeria reported that < 3% of the kidney transplants performed in Nigeria were in children and more than 40% of the children were at least 15 years at the time of transplantation [47•] . In many of the countries with no or limited KTx, it is a common practice for patients whose families could afford it to emigrate to other countries or to get the kidney transplantation done overseas; India represents the most common choice for the latter [48•, 49] . Deceased kidney transplantation is only available in Morocco, Algeria, Tunisia and South Africa [40•] ; this option requires legislation around brain death and its absence in many of the countries negatively impacts the pool of kidney grafts and worsens access of children to KTx.

Diagnostic modalities for kidney disease in children in the continent have improved with widespread availability of sonography. However, modalities such as urodynamics and nuclear medicine scans are still largely unavailable. For example, in Nigeria, there is only one functioning nuclear medicine centre for the country with a population of 211 million [1, 50•] . Medications for kidney diseases have become more available compared to several decades ago, largely as a result of cheaper and good-quality generics. Calcineurin inhibitors, mycophenolic acid and its derivatives, monoclonal antibodies, are now available but remain largely unaffordable to most children and are in tablets or capsule formulations that are not easy to administer to younger children.

Africa has the least density of health manpower in the world. The World Health Organization (WHO) in its Global Health Observatory in 2018 estimated that there were 2.1 medical doctors and 9.94 nurses and midwives per 10,000 population in SSA with North Africa faring slightly better [51•] . However, both regions are well below the global average of 17.54 medical doctors and 39.05 nurses and midwives per 10,000 population. In contrast for example, Europe has 20 times more doctors per 10,000 population than SSA. The population of medical specialists in kidney care is even worse. The global survey conducted by the International Society of Nephrology showed that in 2018, the global median number of nephrologists was 9.95 per million population and 0.6 pmp in Africa [40 ••] . In a recently published textbook, Nephrology Worldwide, the authors reported that the number of nephrologists per million population ranged from 0.22 in Uganda to 2.5 in the Republic of South Africa [52• ]. The picture is bleaker for children who make up 42% of the 1.1 billion population in the continent; the number of paediatric nephrologists per million population is well below 1. For example, in Lagos, Southwest Nigeria, there are only two paediatric nephrologists for the 20 million inhabitants of the state. This is a major challenge not only for clinical management but also for advocacy for children with kidney disease. Furthermore, the few kidney specialists in the continent are found in large hospitals located in urban centres. With about 50% of the continent living in rural areas, most children have no access to kidney care. This is another driver of missed diagnosis of kidney diseases in the continent.

In recent years, professional organisations such as the International Pediatric Nephrology Association (IPNA), International Society of Nephrology (ISN) and International Society of Peritoneal Dialysis (ISPD) have supported the training of manpower in paediatric nephrology in the continent by providing training grants and linking trainees with established centres, mostly in Egypt and South Africa [48, 53•, 54•] . This has resulted in over 35 paediatricians trained in nephrology from South Africa alone. For example, three of the authors (CIE, BA, RE) enjoyed training support from IPNA and ISN to undergo training in paediatric nephrology at Red Cross War Memorial Children's Hospital, Cape Town, South Africa, under two of the authors (PN, MM). In addition, the Saving Young Lives Program, a collaborative effort of these professional associations, has supported the training of teams of medical doctors and nurses in initiating and strengthening acute peritoneal dialysis services in several countries in Africa [55] . The COVID-19 pandemic, despite the immense negative impact on healthcare delivery, has facilitated on-line learning and attendance of virtual congresses which promotes continuing medical education. These learning opportunities were largely previously unavailable to the paediatric nephrologists in low-resource countries who could not afford the cost of travels.

However, despite the modest gain in health manpower for kidney care, like all other aspects of healthcare in the continent, migration to better resourced regions of the world remains a perennial threat. For example, 38% of the hospital doctors in the National Health Service (NHS) in England gained their medical degree outside the UK while 22 out of every 1000 NHS staff identified as Africans [56] . Furthermore, a national poll conducted in Nigeria in 2018 found that 88% of the medical doctors polled were currently seeking to work abroad with the UK, USA and Canada being the top three destinations [57] . The net migration of healthcare workers out of the continent may persist during and after the COVID-19 pandemic as more governments in OECD countries promote faster integration of migrant healthcare workers into their systems [58] . The prospect of better job satisfaction, standard of living and increased income remains potent push factors from the continent. With only 0.4 pmp nephrology trainee reported in Africa, compared with 5.8 pmp in Western Europe, the gap in kidney care in the continent may worsen with time [40 ••, 46] . It is reassuring to note that the feeling of making a difference and helping to build resources in one's own country may counteract these push factors to some degree as the majority of paediatric nephrologists trained by IPNA and ISN have indeed returned and stayed in their countries of origin.

Public spending on health in the continent is among the lowest in the world. In 2018, the WHO estimated that the current health expenditure per capita in Africa was a meagre 132 US dollars [59] . Furthermore, African governments spent the least percentage of its expenditure on health at 6.69%; only four African governments in 2018 spent more than 10% of its domestic expenditure on health [59] . Not surprising, only in six of the 42 African countries surveyed in 2018 by ISN was non-dialysis CKD care funded by the government and free at the point of delivery [40••] . Consequently, for most families in the continent, paying for kidney care is exorbitant, unplanned and out of pocket. In the face of high burden of neonatal morbidities and infection-related diseases such as malaria, pneumonia and diarrhoeal diseases, financing kidney care is not a priority for most African governments and multilateral donor agencies. As a result of the austere level of spending on overall health and kidney care, many children present late to care and are unable to afford essential kidney care. The meagre spending on healthcare contributes to the unavailability of many health diagnostic and therapeutic modalities in the continent. Also, the low spending on healthcare is a major driver of brain drain and a strong disincentive to those aspiring to pursue a career in paediatric nephrology and its allied specialties. Overall, these factors act in concert to worsen the care and outcome of children with kidney diseases in the continent.

Although African governments pledged in 2007 to contribute 1% of their GDP to research and development, the pledge has never been met in almost all the countries in the continent. In 2017, for example, only an average 0.4% of the GDP of SSA was committed to R&D [60] . Funding for research in the continent is uniquely from the public sector like the government and international agencies, unlike in the developed world where the private sector is the major donor source [61] . Major international sources of funding for health research in the continent include the National Institutes of Health (NIH), UK Medical Research Council European and Developing Countries Clinical Trials Partnership and Wellcome Trust [62]; it is not uncommon that the donors' research priorities are sometimes at variance with the continent's priorities. The low funding for research means many important research into the unique paediatric kidney diseases in the continent are not undertaken or they are funded poorly from the researchers' meagre income.

Of notable mention is the ongoing Human Heredity and Health in Africa (H3A) Kidney Disease Research Network (part of the larger H3A consortium) which is funded by the NIH to investigate the genetic and environmental underpinnings of common kidney diseases in Africans in the continent [63• ]. In addition, the research efforts aim to build crucial research capacity in genomics, ethics, social implications of research, bioinformatics, biobanking, networking and academic publication. It is currently enrolling children with idiopathic childhood nephrotic syndrome and sickle cell disease in more than 10 centres in Ghana and Nigeria with centres in South Africa and Cameroon expected to join soon.

Taken together, the unique features of healthcare in the continent support the primacy and cost-effectiveness of measures aimed at preventing and detecting early kidney diseases in children. The measures that may potentially have the most impact on paediatric kidney care in the continent include improving access to safe drinking water and sanitation [64] , use of long-lasting insecticide-treated mosquito nets and prompt treatment of malaria [65] , improving childhood and maternal nutrition especially just before and during pregnancy [66] , increasing facility births and antenatal diagnosis of CAKUT and scaling up routine childhood immunisation and universal healthcare [67, 68] ; where universal healthcare already exists, kidney services should be included in the coverage. In Africa, the continent with the least density of paediatric kidney manpower, training of non-medical doctors and non-paediatric nephrologists to manage children with kidney diseases will have a major salutary effect on kidney outcome as it increases the pool of knowledgeable and skilful manpower and improves access to care.

Paediatric nephrology in Africa has its own peculiar challenges not only in terms of the unique kidney pathologies but also in terms of lack of available treatment modalities including both acute and chronic dialysis and access to transplantation for children. Advocacy for paediatric nephrology remains a priority as adults are often prioritised in the management of kidney disease. Human manpower has improved in the last two decades largely due to training input of international professional organisations. However, sustained support of paediatric nephrologists is needed to prevent them from migrating to better-resourced regions of the world. On-line education and support from training centres as well as attendance of virtual congresses has fostered continuing medical education but affordable investigations including genetic testing, equipment and facilities for paediatric dialysis and kidney transplantation remain a major challenge.

The authors declare no competing interests.

This article is not a report involving human or animal subjects performed by any of the authors.

International Monetary Fund: GDP per capita, current prices

The World Bank: World Bank open data

GDP per capita of African countries 2021

Pattern and outcome of renal diseases in hospitalized children in Khartoum State

Childhood renal disorders in Ghana: a 3-year data review

Pediatric kidney diseases in an African country: prevalence, spectrum and outcome

Highlights the common paediatric kidney diseases in an hot dry region of Nigeria with low routine childhood vaccination coverage

Common mutation causes cystinosis in the majority of black South African patients

Primary hyperoxaluria type 1 in children: clinical classification, renal replacement therapy, and outcome in a single centre experience

Consanguinity and genetic diseases in North Africa and immigrants to Europe

Clinical profile and hospital outcome of children with severe acute kidney injury in a developing country

Acute kidney injury among paediatric emergency room admissions in a tertiary hospital in South West Nigeria: a cohort study

World malaria report. 20 years of global progress and challenges. Geneva: World Health Organization

Acute kidney injury is common in pediatric severe malaria and is associated with increased mortality

This article shows that acute kidney injury is highly prevalent in children with severe malaria and underrecognised using the current WHO criteria

Acute kidney injury in asphyxiated neonates admitted to a tertiary neonatal unit in Sudan

Acute kidney injury in children: 3-year data review from Ghana

Prevalence and outcomes of acute kidney injury in term neonates with perinatal asphyxia

Outcomes of acute kidney injury in children and adults in sub-Saharan Africa: a systematic review. Lancet Glob Health

Paediatric end-stage renal disease in a tertiary hospital in South West Nigeria

Epidemiological, clinical and developmental aspects of chronic kidney disease stages 3-5 (CRF) in children in a pediatric hospital in Senegal

This article highlights the infrequent detection of CAKUT antenatally in children in Africa; less than 5% of the children had antenatal diagnosis of posterior urethral valve in this study 25

Presentation, management, and outcome of posterior urethral valves in a Nigerian tertiary hospital

Renal abnormalities among HIV infected children at Muhimbili National Hospital (MNH)-Dar es Salaam

Chronic kidney disease in the global adult HIV-infected population: a systematic review and meta-analysis

The sytematic review documented the high burden of chronic kidney disease due to HIV in Africa

Kidney function, urinalysis abnormalities and correlates in equatorial Africans with sickle cell disease

The largest to date study involving over 200 Black children with idiopathic childhood nephrotic syndrome in Africa with high rate of steroid sensitivity similar to other races

The initial response to corticosteroid therapy in childhood nephrotic syndrome in Cote D'ivoire

Childhood nephrotic syndrome in tropical Africa: then and now. Paediatr Int Child Health

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa

Juvenile systemic lupus erythematosus in Nigeria

Watson AR. Chronic renal failure in Sudanese children: aetiology and outcomes

The spectrum of chronic kidney disease (stages 2-5) in KwaZulu-Natal

Overview of a paediatric renal transplant programme

Pediatric renal transplantation in a South African teaching hospital: a 20-year perspective

Causes of chronic kidney disease in Egyptian children

Global Kidney Health Atlas: a report by the International Society of Nephrology on the global burden of end-stage kidney disease and capacity for kidney replacement therapy and conservative care acrossworld countries and regions

Peritoneal dialysis for children with acute kidney injury in Lagos, Nigeria: experience with adaptations

Paediatric dialysis services in Nigeria: availability, distribution and challenges

State of renal replacement therapy services in Ghana

A review of policies and programmes for human organ and tissue donations and transplantations, WHO African Region

Global dialysis perspective: Mauritius

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Africa

The current status of kidney transplantation in Nigerian children: still awaiting light at the end of the tunnel

Developing nephrology services in low income countries: a case of Tanzania

Transplant tourism among kidney transplant patients in Eastern Nigeria

Underutilisation of nuclear medicine scans at a regional hospital in Nigeria: need for implementation research. Ecancermedicalscience

The Global Health Observatory: SDG Target 3.c | Health workforce: Substantially increase health financing and the recruitment, development, training and retention of the health workforce in developing countries, especially in least developed countries and small island developing States

Switzerland: Springer Nature Switzerland; 2021. First of its kind to describe nephrology services in 51 countries from all regions of the world from the perspective of the local practitioners

Training nephrologists from developing countries: does it have a positive impact?

Saving Young Lives" with acute kidney injury: the challenge of acute dialysis in low-resource settings

NHS staff from overseas: statistics. NHS Digital

NOIPolls: New survey reveals 8 in 10 Nigerian doctors are seeking work opportunities abroad

Mobility and migration of African health workers post COVID-19

Global Health Observatory: out-ofpocket expenditure as percentage of current health expenditure (CHE) (%)

UIS: Global Investments in R&D

Investing in health R&D: where we are, what limits us, and how to make progress in Africa

Overview of the human heredity and health in Africa Kidney Disease Research Network (H3A-KDRN)

Preventing diarrhoea through better water, sanitation and hygiene: exposures and impacts in lowand middle-income countries

Insecticide-treated nets for preventing malaria

Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? Lancet

Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world

The influence of Universal Health Coverage on Life Expectancy at Birth (LEAB) and Healthy Life Expectancy (HALE): a multicountry cross-sectional study