Search

Steroid-resistant nephrotic syndrome (SRNS) is the most severe form of childhood nephrotic syndrome with an increased risk of progression to chronic kidney disease stage 5. Research endeavors to date have identified more than 80 genes that are associated with SRNS. Most of these genes regulate the structure and function of the podocyte, the visceral epithelial cells of the glomerulus. Although individuals of African ancestry have the highest prevalence of SRNS, especially those from Sub-Saharan Africa (SSA), with rates as high as 30–40% of all cases of nephrotic syndrome, studies focusing on the characterization and understanding of the genetic basis of SRNS in the region are negligible compared with Europe and North America. Therefore, it remains unclear if some of the variants in SRNS genes that are deemed pathogenic for SRNS are truly disease causing, and if the leading causes of monogenic nephrotic syndrome in other populations are the same for children in SSA with SRNS. Other implications of this lack of genetic data for SRNS in the region include the exclusion of children from the region from clinical trials aimed at identifying potential novel therapeutic agents for this severe form of nephrotic syndrome. This review underlines a need for concerted efforts to advance the genetic basis of SRNS in children in SSA. Such endeavors will complement global efforts at understanding the genetic basis of nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Dialysis is potentially lifesaving in children with acute kidney injury (AKI) or chronic kidney disease (CKD), but availability is limited in low-income countries and lower-middle-income countries (LMICs). Methods: In the present study, we perform a 4-year study of patients who received peritoneal dialysis (PD) or haemodialysis (HD) at the Paediatric Nephrology Unit of the University College Hospital Ibadan, Nigeria. Subgroup analysis was performed on patients with sepsis or malaria AKI who underwent HD or PD for predictors of in-hospital mortality. Results: A total of 167 children aged 7 days to 18 years, median 7 (interquartile range 3–12) years, (60.5% males) were studied. In total, 129 (77.2%) had AKI, while 38 had CKD. Regarding AKI, 83 children (64.3%) received HD only, 42 underwent PD only, while 4 underwent both HD and PD. Malaria AKI was treated with HD in 43 (51.8%) or PD in 8 (10.5%), while sepsis AKI was treated with HD in 20 (21.4%) or PD in 33 (78.6%). Mortality in AKI was 16.3% overall, 10.8% in children on HD only, and 26.2% in children on PD only. Patients with sepsis AKI had higher mortality compared to patients with malaria AKI (RR 7.96 [1.70–37.37]). Subgroup analysis showed that age, diagnosis, and dialysis modality were not independent risk factors for mortality. The aetiology of CKD was glomerulonephritis in 26 (68.4%): treatment was HD in 36 and PD in 2 with mortality being 26.3%. Conclusions: PD for AKI showed relatively good outcomes in a LMIC. However, funding and support for a formal dialysis program for the management of AKI and CKD are needed. [ABSTRACT FROM AUTHOR]

Background. First-line treatment for paediatric nephrotic syndrome, a chronic disease characterised by proteinuria, hypoalbuminaemia and oedema, is corticosteroid therapy. An association between African ethnicity and steroid resistance has been reported, but published data from sub-Saharan Africa are limited and lack consensus on the prevalence of steroid-resistant disease. Objective. We aimed to describe a cohort of paediatric patients with nephrotic syndrome, determine the frequency of steroid resistance, and investigate factors associated with steroid resistance at Hospital Central de Maputo, Mozambique. Methods. A retrospective chart review was performed for paediatric patients (1 - 14 years old) admitted with nephrotic syndrome between 2010 and 2015 with at least one follow-up visit by 31 March 2016. Patients with HIV or malaria were excluded. Descriptive statistics and frequencies disaggregated by treatment response were produced. Associations of treatment response with sociodemographic, clinical and laboratory variables were investigated by appropriate univariable statistical tests. Results. Twenty-eight patients met inclusion criteria and were characterised as having steroid-sensitive or steroid-resistant nephrotic syndrome based on response to an initial corticosteroid regimen. There were 15 boys (53.6%) and 13 girls (46.4%), with a median age of 5.5 years. Fifteen (53.6%) were steroid-sensitive, and 13 (46.4%) were steroid-resistant. Steroid-resistant patients had significantly lower diastolic blood pressure (p=0.004), lower serum haemoglobin (p=0.003), lower serum albumin (p=0.03) and higher platelet counts (p=0.008) compared with sensitive cases. Only 4 (30.8%) steroid-resistant patients received a kidney biopsy. Conclusion. Given the relatively high occurrence of steroid resistance in this study, expanding access to kidney biopsy and second-line medications for paediatric patients not in remission after an initial course of corticosteroid therapy is needed to meet the current standard of care. Factors associated with steroid resistance need to be studied prospectively in larger cohorts of Mozambican children. [ABSTRACT FROM AUTHOR]

Background: Non-infectious uveitis is a well-reported cause of blindness in more developed countries, however data from sub-Saharan Africa is lacking. Here we aim to describe the diseases associated with paediatric non-infectious uveitis and the effect of currently available treatment in this setting. Methods: A retrospective observational analysis of children with non-infectious uveitis from January 2010 to December 2017, attending the tertiary paediatric rheumatology and ophthalmology referral units in Cape Town was conducted. Statistical analysis utilising STATA13 software was performed with p < 0.05 considered significant. Results: Twenty-nine children were identified: median age at first visit of 74 months (IQR 49–86 months), female to male ratio of 0.9:1, predominantly of mixed ancestry (72.4%). Juvenile idiopathic arthritis associated uveitis (JIAU) (48.3%), idiopathic uveitis (41.4%), sarcoidosis (6.9%) and Behcet's disease (3.5%) were diagnosed. Chronic anterior uveitis (72.4%) was the most frequent finding. Fifty-five percent had complications at presentation and all children with idiopathic uveitis presented with cataracts. Only 6.5% of the JIA cohort had JIAU. All JIA children had chronic anterior uveitis. There were no differences between JIA children with uveitis and those without uveitis, for sex (p = 0.68) and race (p = 0.58). Significantly, children with uveitis presented at an overall younger age (p = 0.008), had oligo-articular JIA (p = 0.01) and were antinuclear antibody positive (p < 0.001). Children with idiopathic uveitis were predominantly male (66.6%) with chronic anterior uveitis (41.7%). Nineteen children (65.5%) in the cohort had inactive disease on treatment at 12 months from diagnosis, which included 10 on topical corticosteroid therapy. At the last clinical visit 17 (58.6%) on standard initial therapy, 8 (27.6%) on tumour necrosis factor inhibitors and 2 on additional DMARDs were in remission. Five of these children still required topical corticosteroids. Surgery was performed in 41.4%, primarily in the idiopathic group. Visual acuity improved or was maintained on treatment. Conclusion: Current practice seems to detect children with potentially sight-threatening disease but the high rate of complications and the low percentage of children with JIAU raises concerns of delayed healthcare intervention. Tumour necrosis factor inhibitors have improved outcomes in refractory cases in this cohort, however further studies are needed. [ABSTRACT FROM AUTHOR]

Background: Paediatric rheumatic disorders are common in children and result in significant impairment in quality of life, morbidity and mortality. There is limited information on the burden of these disorders in lower income countries especially in sub-Saharan Africa. Few case reports have documented presence of paediatric rheumatic disorders in Tanzania. This study was conducted to determine the spectrum of rheumatic disorders among children at Muhimbili National Hospital (MNH). Methods: This was a retrospective study conducted among children who were attended at MNH between January 2012 and August 2019. Paediatric patients seen in the out-patient clinics and those admitted in the wards were eligible. All patients with diagnosis of rheumatic disorders were identified from admission books and outpatient clinic logbooks, and later data were collected from their case notes and were recorded in clinical research forms. Collected information included age, sex, clinical features and laboratory tests results. Results: A total of 52 children with mean age of 9.5 ± 4.3 years, 12 (40.4%) participants were aged above 10 years and 32 (61.5%) were females. Frequently reported clinical presentations were joint pain 44 (84.6%), joint swelling 34 (65.4%), fever 24 (46.2%) and skin rashes 21(40.4%). Juvenile idiopathic arthritis (JIA) was the predominant diagnosis reported in 28 (53.8%) participants followed by juvenile systemic lupus erythematosus 8 (15.4%), mixed connective tissue diseases 4 (7.7%) and juvenile dermatomyositis 4 (7.7%). Antinuclear antibody test was performed in 16 participants it was positive in 9 (56.2%). Nine participants were tested for anti-double stranded DNA test and 5 (55.6%) were positive for this test. C-reactive protein was tested in 46 participants out of which 32 (69.6%) had elevated levels. HIV was tested in 24 (46.2%) participants and results were negative. Thirty-five out of 52 (67.3%) participants had anaemia. Predominant drugs used for treatment of JIA include prednisolone and methotrexate. Conclusions: Paediatric rheumatic disorders are not uncommon in Tanzania-and were noted to affect more female children in this study. Predominant conditions included juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). [ABSTRACT FROM AUTHOR]

Introduction: The prevalence rates of the common histopathologic subtypes of childhood nephrotic syndrome associated with steroid resistance appear to be changing globally. In Sub Saharan Africa (SSA), the trend is similar over the past few decades. Aim: This systematic review aims to determine the current prevalence rates of the histopathologic subtypes associated with childhood steroid-resistant nephrotic syndrome (SRNS) in SSA. Methods: A search of the PubMed, Google and African Journals Online databases was conducted from January to December 2018 using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow-chart to identify relevant articles which met the aim of the systematic review. A qualitative synthesis and descriptive analysis of the extracted data were then conducted. The mean values for the prevalence rates of the reported histopathologic subtypes were calculated. A meta-analysis was not done due to few numbers of studies reviewed. The review is registered with PROSPERO, number CRD42018111916. Results: In the West African sub-region, the currently reported histopathologic subtypes associated with childhood nephrotic syndrome are focal segmental glomerulosclerosis (FSGS), minimal-change nephropathy (MCN), membrano-proliferative glomerulonephritis (MPGN), membranous nephropathy (MN) and mesangial proliferative glomerulonephritis (MesPGN). The picture is the same in South Africa. More importantly, the predominant histopathologic lesions associated with steroid resistance are FSGS (West Africa) and MCN/FSGS (South Africa), with mean prevalence rates of 57.2% and 36.1% respectively. Conclusion: The prevalence of FSGS is currently high in childhood nephrotic syndrome in SSA. This histopathologic subtype remains the commonest lesion associated with SRNS in this part of the globe. [ABSTRACT FROM AUTHOR]

ABSTRACT Adolescents make up a quarter of the world's population and are important users of health services. In South Africa little is known about the extent of renal disease or outcomes in this group. Adolescents are a vulnerable age group, due to their neurocognitive development, engagement in high-risk social activities, prevalence of mental illness and increasing rates of HIV infection. In Africa access to renal replacement therapy is rationed, therefore the focus of renal disease must be one of prevention rather than dealing with the management of end stage renal disease. Treating adolescents is a challenging field, as compliance is essential as a preventative strategy. This review will outline how a cost effective adolescent service was established in a resource limited setting. The adolescent friendly clinic aims to ease transition of adolescents, improve engagement within the health service and ultimately aims to improve compliance. In order to treat adolescents, it is important to deliver age-appropriate treatment that can be implemented in any chronic disease setting to give the adolescent the greatest chance of success. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis and HIV are both associated with kidney disease. Prevalence and factors associated with abnormal renal function among HIV-infected children in Africa compared to uninfected controls have not been well described in a schistosomiasis endemic area. Methodology/Principal Findings: This cross-sectional study was conducted at the Sekou Toure Regional Hospital HIV clinic in Mwanza, Tanzania. A total of 122 HIV-infected children and 122 HIV-uninfected siblings were consecutively enrolled. Fresh urine was obtained for measurement of albuminuria and Schistosoma circulating cathodic antigen. Blood was collected for measurement of serum creatinine. Estimated glomerular filtration rate (eGFR) was calculated using the modified Schwartz equation. Renal dysfunction was defined operationally as eGFR<60mL/min/1.73m2 and/or albuminuria>20mg/L in a single sample. Among 122 HIV-infected children, 61/122 (50.0%) met our criteria for renal dysfunction: 54/122 (44.3%) had albuminuria>20mg/L and 9/122 (7.4%) had eGFR<60. Among 122 HIV-uninfected children, 51/122 (41.8%) met our criteria for renal dysfunction: 48/122 (39.3%) had albuminuria>20mg/L and 6/122 (4.9%) had eGFR<60. Schistosomiasis was the only factor significantly associated with renal dysfunction by multivariable logistic regression (OR = 2.51, 95% CI 1.46–4.31, p = 0.001). Conclusions/Significance: A high prevalence of renal dysfunction exists among both HIV-infected Tanzanian children and their HIV-uninfected siblings. Schistosomiasis was strongly associated with renal dysfunction. Author Summary: Ninety percent of schistosomiasis occurs in sub-Saharan Africa, where 91% of HIV-infected children reside. Both schistosomiasis and HIV affect the kidney, but their respective effects on kidney disease in children are not well described. Our prior work in HIV-infected adults demonstrated a high prevalence of kidney disease, possibly worsened by schistosomiasis, but adults are less commonly and less heavily infected with schistosomiasis than children. Therefore, we sought to describe the prevalence and factors associated with renal dysfunction (defined operationally as eGFR <60mL/min/1.73m2 and/or albuminuria >20mg/L in a single urine test) among HIV-infected children and their uninfected siblings living in a schistosomiasis endemic area. We found that half of HIV-infected children and more than one third of HIV-uninfected children had renal dysfunction. Schistosomiasis was the only factor significantly associated with renal dysfunction, increasing odds of renal dysfunction by 2.5-fold. Nearly 50% of the renal dysfunction we observed in both groups could be explained by schistosomiasis. The strong association between schistosomiasis and renal dysfunction among both HIV-infected and uninfected children should remind clinicians to screen for schistosomiasis. It also ought to spur further prospective research to assess for causality and outcomes in the relationship between S. mansoni and kidney disease in children. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) are hyperendemic in sub-Saharan Africa. The HBV genotypes prevailing in HIV-infected Africans are unknown. Our aim was to determine the HBV genotypes in HIV-infected participants and to identify clinically significant HBV mutations. From 71 HBV DNA+ve HIV-infected participants, 49 basic core promoter/precore (BCP/PC) and 29 complete S regions were successfully sequenced. Following phylogenetic analysis of 29 specimens in the complete S region, 28 belonged to subgenotype A1 and one to D3. Mutations affecting HBeAg expression at the transcriptional (1762T1764A), translational (Kozak 1809-1812, initiation 1814-1816, G1896A with C1858T), or post translational levels (G1862T), were responsible for the high HBeAg-negativity observed. The G1862T mutation occurred only in subgenotype A1 isolates, which were found in one third (7/21) of HBsAg-ve participants, but in none of the 18 HBsAg+ve participants (p<0.05). Pre-S deletion mutants were detected in four HBsAg+ve and one HBsAg-ve participant/s. The following mutations occurred significantly more frequently in HBV isolated in this study than in strains of the same cluster of the phylogenetic tree: ps1F25L, ps1V88L/A; ps2Q10R, ps2 R48K/T, ps2A53V and sQ129R/H, sQ164A/V/G/D, sV168A and sS174N (p<0.05). ps1I48V/T occurred more frequently in females than males (p<0.05). Isolates with sV168A occurred more frequently in participants with viral loads >200 IU per ml (p<0.05) and only sS174N occurred more frequently in HBsAg-ve than in HBsAg+ve individuals (p<0.05). Prior to initiation of ART, ten percent, 3 of 29 isolates sequenced, had drug resistance mutations rtV173L, rtL180M+rtM204V and rtV214A, respectively. This study has provided important information on the molecular characteristics of HBV in HIV-infected southern Africans prior to ART initiation, which has important clinical relevance in the management of HBV/HIV co-infection in our unique setting. [ABSTRACT FROM AUTHOR]

The article discusses the problems of nephrology practice in Sub-Saharan Africa. It says that lack of resources is a major problem on the renal care in many parts of Africa. Rationing of services is practiced in many parts of Africa, including South Africa, resulting in small numbers of patients selected for renal replacement therapy (RRT). Appropriate training and retention of healthcare workers is another major challenge.