Trends in the epidemiology of childhood nephrotic syndrome in Africa: A systematic review.

Background: Childhood nephrotic syndrome, if left untreated, leads to progressive kidney disease or death. We quantified the prevalence of steroid-sensitive nephrotic syndrome, steroid-resistant nephrotic syndrome, and histological types as the epidemiology of nephrotic syndrome in Africa remains unknown, yet impacts outcomes. Methods: We searched MEDLINE, Embase, African Journals Online, and WHO Global Health Library for articles in any language reporting on childhood nephrotic syndrome in Africa from January 1, 1946 to July 1, 2020. Primary outcomes included steroid response, biopsy defined minimal change disease, and focal segmental glomerulosclerosis (FSGS) by both pooled and individual proportions across regions and overall. Findings: There were 81 papers from 17 countries included. Majority of 8131 children were steroid-sensitive (64% [95% CI: 63-66%]) and the remaining were steroid-resistant (34% [95% CI: 33-35%]). Of children biopsied, pathological findings were 38% [95% CI: 36-40%] minimal change, 24% [95% CI: 22-25%] FSGS, and 38% [95% CI: 36-40%] secondary causes of nephrotic syndrome. Interpretation: Few African countries reported on the prevalence of childhood nephrotic syndrome. Steroid-sensitive disease is more common than steroid-resistant disease although prevalence of steroid-resistant nephrotic syndrome is higher than reported globally. Pathology findings suggest minimal change and secondary causes are common. Scarcity of data in Africa prevents appropriate healthcare resource allocation to diagnose and treat this treatable childhood kidney disease to prevent poor health outcomes. Funding: Funding was provided by the Canadian Institute for Health Research (CIHR) and the National Institute of Health (NIH) for the H3 Africa Kidney Disease Research Network. This research was undertaken, in part, from the Canada Research Chairs program.

Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome.

To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.90) and TNFSF15 (rs6478109, P=2.54E-8, OR=0.72) regions achieved genome-wide significance and were replicated in Korean, South Asian and African populations. Trans-ethnic meta-analyses including Japanese, Korean, South Asian, African, European, Hispanic and Maghrebian populations confirmed the significant associations of variants in NPHS1-KIRREL2 (Pmeta=6.71E-28, OR=1.88) and TNFSF15 (Pmeta=5.40E-11, OR=1.33) loci. Analysis of the NPHS1 risk alleles with glomerular NPHS1 mRNA expression from the same person revealed allele specific expression with significantly lower expression of the transcript derived from the risk haplotype (Wilcox test p=9.3E-4). Because rare pathogenic variants in NPHS1 cause congenital nephrotic syndrome of the Finnish type (CNSF), the present study provides further evidence that variation along the allele frequency spectrum in the same gene can cause or contribute to both a rare monogenic disease (CNSF) and a more complex, polygenic disease (SSNS).

Overview of paediatric urology practice in lagos state university teaching hospital, Ikeja, Lagos, Nigeria.

INTRODUCTION: Paediatric urology is one of the subspecialities of urology, and in most climes, it is practised by the urologists and paediatric surgeons, and likewise in the Lagos State University Teaching Hospital (LASUTH). The urologists see and manage most of these cases in LASUTH. There has been no formal training in this subspeciality. However, both the urologists and paediatric surgeons in LASUTH have acquired some measure of skill and experience over time by virtue of the relatively high volume of the cases seen. This study is aimed at reviewing the practice of paediatric urology in the urology division of LASUTH and to advocate for formal training in an otherwise rare but direly needed subspeciality. PATIENTS AND METHODS: The ports of entry of paediatric patients with urologic conditions were assessed retrospectively over a 5-year period (2014-2018). The paediatric age range based on the Lagos State Government policy for health care is from birth to 12 years old. The ports of entry included the urologic outpatient department, paediatric and the adult surgical emergency units and the paediatric wards. Patients referred to and managed by the paediatric surgery division were excluded from this study. RESULTS: The total paediatric urology cases seen and managed by the urologist in LASUTH within the period of review were 421. A total of 363 paediatric urology cases were seen during the period under review, making up 7.96% of the urology cases seen at the surgical outpatient department. The most common cases managed were hypospadias, posterior urethral valves and hydronephrosis. A variety of other cases include priapism, circumcision and post-circumcision injuries, urethral prolapse, testicular torsion, cystic renal dysplasia, disorder of sexual differentiation and several others. Three hundred and seven surgical procedures were done in the period of review on 272 (64.6%) patients. CONCLUSION: There is a need for subspecialisation in paediatric urology to harness more specialists with a specific focus, training and interest in children and their urological conditions.

Genetic Testing for Steroid-Resistant-Nephrotic Syndrome in an Outbred Population.

Background: Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children and young adults. Despite advances in genomic science that have led to the discovery of >50 monogenic causes of SRNS, there are no clear guidelines for genetic testing in clinical practice. Methods: Using high throughput sequencing, we evaluated 492 individuals from 181 families for mutations in 40 known SRNS genes. Causative mutations were defined as missense, truncating, and obligatory splice site variants with a minor allele frequency <1% in controls. Non-synonymous variants were considered pathogenic if determined to be deleterious by at least two in silico models. We further evaluated for differences in age at disease onset, family history of SRNS or chronic kidney disease, race, sex, renal biopsy findings, and extra-renal manifestations in subgroups with and without disease causing variants. Results: We identified causative variants in 40 of 181 families (22.1%) with SRNS. Variants in INF2, COL4A3, and WT1 were the most common, accounting for over half of all causative variants. Causative variants were identified in 34 of 86 families (39.5%) with familial disease and 6 of 95 individuals (6.3%) with sporadic disease (χ2 p < 0.00001). Family history was the only significant clinical predictor of genetic SRNS. Conclusion: We identified causative mutations in almost 40% of all families with hereditary SRNS and 6% of individuals with sporadic disease, making family history the single most important clinical predictors of monogenic SRNS. We recommend genetic testing in all patients with SRNS and a positive family history, but only selective testing in those with sporadic disease.

Three cases of prune belly syndrome at the Lagos State University Teaching Hospital, Ikeja.

Prune belly syndrome (PBS) is a rare congenital disorder affecting 2.5 to 3.8/100,000 live births worldwide. Our objective of this report is to describe clinical manifestation, laboratory, and radiological characteristics of PBS in our patients, to highlight the limitations to offering appropriate patient care due to parents demanding discharge against medical advice and the need to increase the awareness regarding this rare disease. We report three cases; all referred after birth with lax abdominal wall, congenital anomalies of kidney, and urinary tract. One of the patients had an absent right foot. They all had cryptorchidism, and in one, there was deranged renal function. The reported cases had both medical and radiological interventions to varying degrees. They all had an abdominal ultrasound which revealed varying degrees of hydronephrosis, hydroureters, and bladder changes. Voiding cystourethrogram showed vesicoureteric reflux in one of the reported cases. Urinary tract infections were appropriately treated with antibiotics based on sensitivity. PBS management in our setting remains a challenge because of strong cultural beliefs, and high rate of discharge against medical advice. Focus should be on parent education, early diagnosis, and multidisciplinary management approach.

Serum cystatin C levels in Healthy Nigerian neonates: Is there a need for normative values in Nigerian babies?

Cystatin C is an endogenous marker of renal function. Normal reference values have been documented in neonates outside Africa, but no study has been documented in African neonates. With reports that race may affect serum cystatin C values, this study was carried out to generate normal values in apparently healthy term neonates at birth and three days of life neonates in Nigeria. This was a hospital-based prospective study. A cohort of 120 apparently healthy term neonates were recruited at birth. Serum cystatin C was measured from the cord blood at birth and venous blood when they were three days old using enzyme-linked immunosorbent assay (ELISA) method. The mean serum cystatin C values for cord blood and 3rd day venous samples were 1.67 ± 0.52 mg/L and 1.62 ± 0.52 mg/L, respectively (P = 0.87). The cord blood and 3rd day serum cystatin C values for males were 1.67 ± 0.47 mg/L and 1.68 ± 0.51 mg/L, respectively (P = 0.77) and the values for females were 1.68 ± 0.56 mg/L and 1.58 ± 0.52 mg/L, respectively (P = 07.22). The serum cystatin C levels were similar among the different birth weight groups and gestational age (P >0.05). The cord blood and 3rd day serum cystatin C values were similar. Serum cystatin C values were independent of gender and birth weight of neonates. The values of serum cystatin C in Nigerian neonates were comparable to that reported for neonates in other regions of the world. It is recommended that ELISA technique may be reliably used to measure serum cystatin C levels in neonates.