HBV and proteinuria in relatives and contacts of children with hepatitis B virus-associated membranous nephropathy

HBV and proteinuria in relatives and contacts of children with hepatitis B virus-associated membranous nephropathy.BackgroundHepatitis B virus (HBV)-associated membranous nephropathy (HBVMN) is an important cause of childhood nephrotic syndrome in regions endemic for the virus, but little is understood of the biosocial context in which the disease develops. We evaluated HBV status and proteinuria in family members and household contacts of index children with HBVMN to test the hypothesis that HBV carriage and asymptomatic proteinuria are closely linked and may be causally associated.MethodsThirty-one black children with biopsy-proven HBVMN were the index cases. One hundred and fifty-two family members and 43 black household contacts were the subjects of the study. We assessed HBV carrier status by testing for HBV antigens and antibodies using enzyme-linked immunosorbent assays (ELISA) and for HBV DNA by using slot-blot hybridization and the polymerase chain reaction. Sequencing of the precore region of HBV was done in a subset of both index cases and subjects. Proteinuria was assessed by measuring the urinary protein/creatinine ratio.ResultsSeventy-two (37%) of the 195 family members and household contacts were HBV carriers, and 53 (27%) had a protein/creatinine ratio greater than the physiological limit. The frequency of abnormal proteinuria was not significantly different in those with [22 out of 72 (30.5%)] or without [33 out of 104 (32%)] HBV carriage. This lack of association remained when carriers were classified into those who were HBsAg positive only and those with active viral replication (HBsAg and/or HBeAg and/or HBV DNA; P = 0.01). Family members were more predisposed to HBV carriage than household contacts, but abnormal proteinuria was present with equal frequency (P = 0.48). Age had a significant impact on proteinuria, with children less than five years being more likely to have abnormal proteinuria (P = 0.008). The prevalence of abnormal proteinuria in family members and household contacts of the index cases was more than that in community-based controls. The 10 index HBVMN cases and the 14 family members and household contacts who were tested all had HBV of genotype A.ConclusionThese results suggest that the family members and household contacts of children with HBVMN are at very high risk of HBV carriage; they also have asymptomatic proteinuria at a significantly higher rate than community-based controls. The HBV carrier status was not associated with proteinuria, a finding supported by peak prevalences of proteinuria in those under five years but no corresponding peak for HBV carriage. Proteinuria may indicate glomerular basement membrane dysfunction. Environmental and social factors may underpin development of these two covert disorders, but are insufficient to account for the index cases of HBVMN. The emergence of children with HBVMN from such households additionally depends on unidentified and possibly genetic factors

Trends in the nephrologist workforce in South Africa (2002–2017) and forecasting for 2030

Background: The growing global health burden of kidney disease is substantial and the nephrology workforce is critical to managing it. There are concerns that the nephrology workforce appears to be shrinking in many countries. This study analyses trends in South Africa for the period 2002–2017, describes current training capacity and uses this as a basis for forecasting the nephrology workforce for 2030. Methods: Data on registered nephrologists for the period 2002 to 2017 was obtained from the Health Professions Council of South Africa and the Colleges of Medicine of South Africa. Training capacity was assessed using data on government-funded posts for nephrologists and nephrology trainees, as well as training post numbers (the latter reflecting potential training capacity). Based on the trends, the gap in the supply of nephrologists was forecast for 2030 based on three targets: reducing the inequalities in provincial nephrologist densities, reducing the gap between public and private sector nephrologist densities, and international benchmarking using the Global Kidney Health Atlas and British Renal Society recommendations. Results: The number of nephrologists increased from 53 to 141 (paediatric nephrologists increased from 9 to 22) over the period 2002–2017. The density in 2017 was 2.5 nephrologists per million population (pmp). In 2002, the median age of nephrologists was 46 years (interquartile range (IQR) 39–56 years) and in 2017 the median age was 48 years (IQR 41–56 years). The number of female nephrologists increased from 4 to 3 and the number of Black nephrologists increased from 3 to 24. There have been no nephrologists practising in the North West and Mpumalanga provinces and only one each in Limpopo and the Northern Cape. The current rate of production of nephrologists is eight per year. At this rate, and considering estimates of nephrologists exiting the workforce, there will be 2.6 nephrologists pmp in 2030. There are 17 government-funded nephrology trainee posts while the potential number based on the prescribed trainer-trainee ratio is 72. To increase the nephrologist density of all provinces to at least the level of KwaZulu-Natal (2.8 pmp), which has a density closest to the country average, a projected 72 additional nephrologists (six per year) would be needed by 2030. Benchmarking against the 25th centile (5.1 pmp) of upper-middle income countries (UMICs) reported in the Global Kidney Health Atlas would require the training of an additional eight nephrologists per year. Conclusions South Africa has insufficient nephrologists, especially in the public sector and in certain provinces. A substantial increase in the production of new nephrologists is required. This requires an increase in funded training posts and posts for qualified nephrologists in the public sector. This study has estimated the numbers and distribution of nephrologists needed to address provincial inequalities and achieve realistic nephrologist density targets

Experience with tacrolimus in children with steroid-resistant nephrotic syndrome

Children with steroid-resistant nephrotic syndrome (SRNS) are at risk of developing renal failure. We report here the results of a single-center retrospective observational study of the remission rate in pediatric patients with SNRS receiving tacrolimus. Serial renal biopsies from children on tacrolimus therapy were evaluated for tubulointerstitial fibrosis and transforming growth factor-β immunostaining. Of the 16 children with SRNS, 15 went into complete remission after a median of 120 days of therapy. Nine children were able to stop steroids, while the others were on tapering doses. Forty-seven percent had relapses, most of which were steroid-responsive. Serial renal biopsies were obtained from seven children after a median treatment duration of 24 months; two of these children had increased tubulointerstitial fibrosis and four showed increased transforming growth factor-β tissue staining. Children with worsening histological findings were younger. There was no significant association between tacrolimus exposure and biopsy changes, although the average trough level was higher in those children with worsening histological findings. In conclusion, tacrolimus may be a safe and effective alternative agent for inducing remission in children with SRNS. However, caution needs to be taken when prescribing this agent due to its narrow therapeutic index. Serial renal biopsies are necessary to check for subclinical nephrotoxicity, especially in younger children and those with higher trough levels

Liddle’s-Like Syndrome Associated With Nephrotic Syndrome in a Pediatric Patient

Nephrotic syndrome, especially the steroid-resistant form, is often complicated by hypertensionin childhood. The syndrome is common in black children. However, the histopathologicalfinding of membranous nephropathy in children with nephrotic syndrome is rare. Liddle’ssyndrome is a rare genetic abnormality that presents with salt-sensitive hypertension causedby constitutive activation of the amiloride-sensitive epithelial sodium channel. The epithelialsodium channel comprises homologous α, β, and γ subunits that share similar structures.Gene mutations associated with Liddle’s syndrome occur in either the β or γ subunits anddisturb or truncate a conserved proline-rich sequence (i.e., PY motif), leading to constitutiveactivation of the epithelial sodium channel. The association of nephrotic syndrome withLiddle’s syndrome has only been described in an adult patient. We present here the first caseof these two syndromes (nephrotic syndrome and Liddle’s-like syndrome) co-existing in achild with membranous nephropathy in his histopathological finding on kidney biopsy

Case report of a child with nephronophthisis from South Africa

Abstract Background Nephronophthisis (NPHP) is an autosomal recessive disorder with a subset of patients presenting with extrarenal manifestations such as retinal degeneration, cerebella ataxia, liver fibrosis, skeletal abnormalities, cardiac malformations, and lung bronchiectasis. However, the involvement of other organ systems has also been documented. Extrarenal manifestations occur in approximately 10–20% of patients. In developed countries, it has been reported as one of the most common causes of monogenic chronic kidney failure (CKF) during the first three decades of life, with more than 25 genes associated with this condition. The current treatment options for managing NPHP include supportive care, management of complications, and kidney replacement therapy when necessary. The index patient is a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain. Her elder sister, TN, who was 17 years old, was diagnosed with CKF and noted to have persistently elevated liver enzymes (gamma-glutamyl transferase, alanine, and aspartate transaminases). Following genetic testing, her elder sister was shown to have Nephronophthisis Type 3, and a liver biopsy showed early fibrotic changes. Subsequent genetic testing confirmed the index patient as having NPHP Type 3. A kidney biopsy showed focal sclerosed glomeruli with patchy areas of tubular atrophy and related tubulointerstitial changes in keeping with NPHP. We present the first confirmatory case of NPHP from South Africa based on histopathology and genetic testing in a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain, whose elder sister also presented with CKF and early liver fibrosis, confirmed on biopsy and genetic testing. Conclusion In low-middle-income countries, genetic testing should be undertaken whenever possible to confirm the diagnosis of NPHP, especially in those with a suggestive biopsy or if there is CKF of unknown aetiology with or without extra-renal manifestations

Nephrotic Syndrome in South African Children: Changing Perspectives in the New Millennium

The epidemiological landscape of nephrotic syndrome (NS) in South Africa has changed drastically in the New Millennium. Although the pattern of disease in the 3 main non-Black racial groups (White, Indian, and Mixed race) mirror that seen in Western countries, Black African children show a pattern of disease that is at variance with these 3 racial groups. The incidence of infectious diseases, particularly hepatitis B virus associated nephropathy has sharply declined to being almost extinct in Black children in the New Millennium whereas HIV-related nephropathy surfaced. However, following the widespread use of anti-retroviral therapy, its incidence has also decreased dramatically. Focal segmental glomerulosclerosis (FSGS), which was once uncommon, has, in the New Millennium, emerged as one of the most challenging forms of NS across all racial groups, particularly in Black children. Although the introduction of calcineurin inhibitors, mycophenolate mofetil and monoclonal antibodies (e.g., rituximab) has improved the outcome of children with FSGS, the reponse in Black children is less than optimal, with those having single gene mutations being universally unresponsive to all forms of immunosuppression. Key Words: children, hepatitis B, HIV, nephrotic syndrom

Prevalence of Primary Hypertension and Risk Factors in Grade XII Learners in KwaZulu-Natal, South Africa

Hypertension in childhood leads to hypertension in adult life, the strongest risk factor being obesity. This study determined the prevalence of primary hypertension and its risk factors in Grade XII learners in KwaZulu-Natal, South Africa, from March 2016 to June 2017. Weight, height, body mass index (BMI), random finger prick cholesterol and glucose, and spot urine for an albumin : creatinine ratio were measured. An average of three separate blood pressure readings taken was at least 5 minutes apart. Five hundred and sixty-four learners had weight, height, and BMI; 536 had random blood glucose; and 545 had cholesterol and random spot urine albumin : creatinine ratios measured. Prehypertension was detected in 168 (29.7%) and hypertension in 77 (13.7%) of learners. Ninety (15.9%) were overweight and 75 (13,3%) were obese. Hypercholesterolaemia was present in 58 (10.8%) and a high spot random urine albumin : creatinine ratio in 5 (1.0%). None had a high blood glucose level. Both prehypertension and hypertension in all learners showed a significant increase with increasing BMI. Six (1.0%) learners had metabolic syndrome. Female learners in other racial groups (defined as Indian, mixed race, and White learners), overweight, and obese learners showed significantly higher rates of hypercholesterolaemia. We showed overweight and obesity as risk factors for prehypertension and hypertension. This presages the need for an appropriate diet and adequate exercise in a child’s school career

Additional file 2: Figure S2. of tarSVM: Improving the accuracy of variant calls derived from microfluidic PCR-based targeted next generation sequencing using a support vector machine

Comparison of quality by depth (QD) from CAKUT and ExAC. Sites that were filtered out of ExAC (VQSR filtering) are shown in red. Sites that were marked as “PASS” in ExAC are shown in gold. Sites that were Not Sanger validated are shown in green. Sites that were Sanger Validated are shown in teal. Sites filtered by tarSVM are shown in blue. Sites that passed tarSVM are shown in purple. Quality by depth is correlated with mean allele balance, as is being used as a proxy for it. It is clear that there is a very clear separation between variants that are filtered by tarSVM and variants that pass tarSVM. Most of the variants filtered by tarSVM have a much lower quality than the pass variants. Variants that are Sanger validated are stronger correlated with variants that pass tarSVM. Variants that are labeled “PASS” in ExAC have a higher variant quality that the microfluidic data. The filtered variants in ExAC have a more flat distribution that those filtered by tarSVM. It is important to note, the variants that underwent Sanger sequencing were selected because they had the characteristics of true variants. This is why there is so much overlap between the distributions for Sanger validated variants and Not Sanger validated variants. (PPTX 121 kb

Additional file 2: Figure S2. of tarSVM: Improving the accuracy of variant calls derived from microfluidic PCR-based targeted next generation sequencing using a support vector machine

Comparison of quality by depth (QD) from CAKUT and ExAC. Sites that were filtered out of ExAC (VQSR filtering) are shown in red. Sites that were marked as “PASS” in ExAC are shown in gold. Sites that were Not Sanger validated are shown in green. Sites that were Sanger Validated are shown in teal. Sites filtered by tarSVM are shown in blue. Sites that passed tarSVM are shown in purple. Quality by depth is correlated with mean allele balance, as is being used as a proxy for it. It is clear that there is a very clear separation between variants that are filtered by tarSVM and variants that pass tarSVM. Most of the variants filtered by tarSVM have a much lower quality than the pass variants. Variants that are Sanger validated are stronger correlated with variants that pass tarSVM. Variants that are labeled “PASS” in ExAC have a higher variant quality that the microfluidic data. The filtered variants in ExAC have a more flat distribution that those filtered by tarSVM. It is important to note, the variants that underwent Sanger sequencing were selected because they had the characteristics of true variants. This is why there is so much overlap between the distributions for Sanger validated variants and Not Sanger validated variants. (PPTX 121 kb