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Background: Steroid-resistant nephrotic syndrome (SRNS) is characterized by unrelieved proteinuria after an initial 4–8 weeks of glucocorticoid therapy. Genes in podocytes play an important role in causing SRNS. Objective: This study aimed to report a pathogenic mutation in SRNS patients and investigate its effects on podocytes, as well as the pathogenic mechanism. Methods: We screened out a novel mutation by using whole-exon sequencing in the SRNS cohort and verified it via Sanger sequencing. Conservative analysis and bioinformatic analysis were used to predict the pathogenicity of the mutation. In vitro, stable podocyte cell lines were constructed to detect the effect of the mutation on the function of the podocyte. Moreover, an in vivo mouse model of podocyte ANLN gene knockout (ANLNpodKO) was used to confirm clinical manifestations. Transcriptome analysis was performed to identify differential gene expression and related signaling pathways. Results: ANLN E841K was screened from three unrelated families. ANLN E841K occurred in the functional domain and was predicted to be harmful. The pathological type of A-II-1 renal biopsy was minimal change disease, and the expression of ANLN was decreased. Cells in the mutation group showed disordered cytoskeleton, faster cell migration, decreased adhesion, increased endocytosis, slower proliferation, increased apoptosis, and weakened interaction with CD2 association protein. ANLNpodKO mice exhibited more obvious proteinuria, more severe mesangial proliferation, glomerular atrophy, foot process fusion, and increased tissue apoptosis levels than ANLNflox/flox mice after tail vein injection of adriamycin. Upregulated differentially expressed genes in cells of the mutation group were mainly enriched in the PI3K-AKT pathway. Conclusion: The novel mutation known as ANLN E841K affected the function of the ANLN protein by activating the PI3K/AKT/mTOR/apoptosis pathway, thus resulting in structural and functional changes in podocytes. Our study indicated that ANLN played a vital role in maintaining the normal function of podocytes. CZoZEd4ExGAZZkosMrZTAE Video Abstract [ABSTRACT FROM AUTHOR]

Membranous nephropathy is an autoimmune disease affecting the glomeruli and is one of the most common causes of nephrotic syndrome. In the absence of any therapy, 35% of patients develop end-stage renal disease. The discovery of autoantibodies such as phospholipase A2 receptor 1, antithrombospondin and neural epidermal growth factor-like 1 protein has greatly helped us to understand the pathogenesis and enable the diagnosis of this disease and to guide its treatment. Depending on the complications of nephrotic syndrome, patients with this disease receive supportive treatment with diuretics, ACE inhibitors or angiotensin-receptor blockers, lipid-lowering agents and anticoagulants. After assessing the risk of progression of end-stage renal disease, patients receive immunosuppressive therapy with various drugs such as cyclophosphamide, steroids, calcineurin inhibitors or rituximab. Since immunosuppressive drugs can cause life-threatening side effects and up to 30% of patients do not respond to therapy, new therapeutic approaches with drugs such as adrenocorticotropic hormone, belimumab, anti-plasma cell antibodies or complement-guided drugs are currently being tested. However, special attention needs to be paid to the choice of therapy in secondary forms or in specific clinical contexts such as membranous disease in children, pregnant women and patients undergoing kidney transplantation. [ABSTRACT FROM AUTHOR]

Objective: To conduct a comprehensive systematic review and meta-analysis of the available literature on the anthropometric nutritional status of South African infants and children, 0–18 years old and to report on trends of changes in nutritional status over the period 1997–2022. Design: Systematic review and meta-analysis. Setting: Review of the available literature on the anthropometric nutritional status of South African infants and children, 0–18 years old, over the period 1997–2022. Participants: South African infants and children, 0–18 years old. Results: Only quantitative data from ninety-five publications that described the nutritional status in terms of anthropometry were included. Most recent studies applied the WHO 2006 and 2007 definitions for malnutrition among children 0–5 years old and 5–19 years old, respectively. Meta-analysis of all prevalence data shows the highest stunting prevalence of 25·1 % among infants and preschool children, compared to 11·3 % among primary school-age children and 9·6 % among adolescents. Furthermore, the overweight and obesity prevalence was similar among children younger than 6 years and adolescents (19 %), compared to 12·5 % among primary school-age children. In national surveys, adolescent overweight prevalence increased from 16·9 % in 2002 to 23·1 % in 2011. Meta-regression analysis shows a decrease in stunting among children 6–18 years old and an increase in combined overweight and obesity in the 10–19 years age group. Conclusion: The double burden of malnutrition remains evident in South Africa with stunting and overweight/obesity the most prevalent forms of malnutrition among children. [ABSTRACT FROM AUTHOR]

Background: Whilst malaria is a prominent aetiology associated with acute kidney injury (AKI) in many parts of Africa, a shift in the traditional AKI aetiologies has been witnessed in sections of the continent. Additionally, limited access to dialysis worsens patient outcomes in these low-resource settings. This retrospective cross-sectional study aimed to determine the associated aetiologies, predictors of need for dialysis and malaria-associated AKI (MAKI), and outcomes of AKI and dialysis among children evaluated by the renal service in Lusaka, Zambia. Methods: The study sampled all children aged 16 years or below, diagnosed with AKI between 2017 and 2021, by the renal unit at the University Teaching Hospitals- Children's Hospital (UTH-CH), and retrospectively abstracted their records for exposures and outcomes. AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria. Frequency and percentage distributions were used to describe the occurrence of AKI aetiologies and treatment outcomes. Predictors of the need for dialysis, MAKI, and poor treatment outcome were identified by using multivariable logistic regression models. Results: A total of 126 children diagnosed with AKI were included in this study. Malaria was the most frequent aetiology of AKI(61.1% (77/126, 95% Confidence Interval (CI): 52.0%-69.7%)). Of the 126 children with AKI, 74.6% (94) underwent dialysis. Predictors of the need for dialysis were oliguria (p = 0.0024; Odds ratio (OR) = 7.5, 95% CI: 2.1–27.7) and anuria (p = 0.0211; OR = 6.4, 95% CI = 1.3, 30.7). A fifth (18.3%, 23/126) of the children developed chronic kidney disease (CKD), 5.6% (7/126) died and, a year later, 77% (97/126) were lost to follow-up. Conclusion: At UTH-CH, malaria is the most frequent aetiology among children with AKI undergoing dialysis and children from low-medium malaria incidence areas are at risk; a considerable proportion of children with AKI need dialysis and Tenchoff catheter use in AKI is advocated. [ABSTRACT FROM AUTHOR]

Background: Intravenous steroid pulses (SP) are successfully used for the treatment of patients with idiopathic nephrotic syndrome (INS) resistant to oral prednisone., Methods: We performed a retrospective analysis of all patients in the three pediatric nephrology centers of the Paris region from 2002 to 2022 who were resistant to a 30-day course of oral prednisone and who received SP for their first INS flare and analyzed their disease course over 4 years., Results: Forty-seven patients (17 girls), median age 3.4 years, were analyzed. Of them, 68% reached remission within 7 days of SP. No significant short-term side effects were noted. Half of the patients started immunosuppressive treatment immediately after their first remission and 62% of them relapsed at least once, whereas all the patients who did not receive immunosuppressive treatment since their first remission relapsed. Among the SP-sensitive patients, 75% needed calcineurin inhibitor (CNI) or B-cell depletion during their disease course to achieve stable remission. Forty-two percent of the whole cohort received B-cell-depleting agents. Among the 15 SP-resistant patients, all received CNI. Twelve/fifteen patients reached remission. After 4 years, 68% among the SP-sensitive patients and 87% of SP-resistant patients still had an active disease., Conclusions: SP are helpful to obtain rapid remission in pediatric INS patients resistant to oral steroids. However, as most SP-sensitive patients need immunosuppressive drugs, mainly CNI and B-cell-depleting agents it could be interesting to discuss the possibility to start CNI directly after the 30-day course of prednisone instead of SP., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

It is well known that minimal change disease (MCD) and focal segmental glomerulosclerosis are the most common histopathology findings in children with idiopathic nephrotic syndrome. Moreover, several studies demonstrated that MCD is associated with high steroid-responsiveness and a low incidence of kidney failure, suggesting that routine kidney biopsy is not warranted. Over time, the indications for performing a kidney biopsy have become increasingly stringent, aiming to limit unnecessary invasive procedures in the paediatric population. The most recent guidelines state that a kidney biopsy is not usually necessary at disease onset. Still, it should be performed in case of atypical features suggestive of systemic diseases or glomerulonephritis and in case of steroid-resistance, to assess the different differential diagnoses, regardless of patient age. Moreover, it has been shown that the best prognostic marker in childhood nephrotic syndrome is response to treatment and that kidney histology is not accurate in predicting prognosis. Furthermore, a kidney biopsy is not necessary to predict the relapsing course. Notably, kidney biopsy is an invasive procedure and may lead to significant complications. Finally, novel non-invasive biomarkers have been validated or are in the process of being approved to guide differential diagnoses and thus limit the need for kidney biopsies in patients with typical nephrotic syndrome. In the following sections, we aim to explain why initiating steroid treatment as the initial approach in teenagers with typical nephrotic syndrome is a reasonable strategy. Additionally, we explore how kidney biopsy indications may be alleviated in this population., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Kidney biopsy plays a crucial role in the diagnosis and management of several glomerular diseases. While it is generally considered a routine and safe procedure in children, it should be conducted with the primary objective of addressing the following question: do the prognosis and treatments vary based on the findings of kidney biopsy? In children presenting with idiopathic nephrotic syndrome (INS), guidelines suggest to consider kidney biopsy for individuals older than 12 years, primarily due to the possible increased incidence of different glomerulonephritis compared to younger patients, who predominantly manifest with minimal change disease. However, these guidelines also advocate for uniform therapeutic strategies, typically steroids, irrespective of the age or histological findings. Whether the age of more than 12 years may be a recommendation for performing kidney biopsy at presentation of INS is debatable. Instead, kidney biopsy could be reserved for steroid-resistant cases. On the other hand, when kidney biopsy is performed in INS, particularly in focal segmental glomerulosclerosis, histology may reveal additional lesions, that are strongly associated with a poorer response to treatment and worse clinical outcomes. Therefore, current guidelines on treatments of nephrotic syndrome may appear overly restrictive, despite the relevant findings provided by kidney biopsy. Therefore, in the present manuscript, which is part of a pro-con debate on the management of nephrotic syndrome in adolescents, we emphasize the potential role of performing a kidney biopsy before initiating corticosteroid treatment., (© 2024. The Author(s).)

Primary glomerular diseases are rare entities. This has hampered efforts to better understand the underlying pathobiology and to develop novel safe and effective therapies. NEPTUNE is a rare disease network that is focused on patients of all ages with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. It is a longitudinal cohort study that collects detailed demographic, clinical, histopathologic, genomic, transcriptomic, and metabolomic data. The goal is to develop a molecular classification for these disorders that supersedes the traditional pathological features-based schema. Pediatric patients are important contributors to this ongoing project. In this review, we provide a snapshot of the children and adolescents enrolled in NEPTUNE and summarize some key observations that have been made based on the data accumulated during the study. In addition, we describe the development of NEPTUNE Match, a program that aims to leverage the multi-scalar information gathered for each individual patient to provide guidance about potential clinical trial participation based on the molecular characterization and non-invasive biomarker profile. This represents the first organized effort to apply principles of precision medicine to the treatment of patients with primary glomerular disease. NEPTUNE has proven to be an invaluable asset in the study of glomerular diseases in patients of all ages including children and adolescents., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD., Methods: In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3-5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis., Results: A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m 2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure., Conclusions: Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors., (© 2024. The Author(s).)

Background: Levamisole is a commonly used steroid-sparing agent (SSA), but the reported incidence of antineutrophil cytoplasmic antibody (ANCA) positivity has been concerning., Methods: Observational cross-sectional study wherein children aged 2 to 18 years with frequently relapsing/steroid dependent nephrotic syndrome (FRNS/SDNS) on levamisole for ≥ 12 months were tested for ANCA., Results: A total of 210 children (33% female), median age of 7.3 (IQR: 5.6-9.6) years, and a median duration of levamisole exposure of 21 (IQR: 15-30) months were tested. ANCA was positive in 18% (n = 37): 89% (n = 33) perinuclear ANCA (pANCA), 3% (n = 1) cytoplasmic ANCA (cANCA), and 8% (n = 3) both. Of ANCA-positive children, none had reduced eGFR or abnormal urinalysis. The majority of these children were asymptomatic (81%, n = 30). Rash was more common among ANCA-positive children [6/37 (16%) vs. 3/173 (2%), p = 0.0001]. On multivariate analysis, higher age (OR = 1.02, [95th CI: 1.01 to 1.03], p = 0.007) and longer duration of levamisole exposure (OR = 1.05, [95th CI: 1.02 to 1.08], p = 0.0007) were associated with ANCA positivity. Levamisole was stopped in ANCA-positive children with the resolution of any clinical manifestations if present. Repeat ANCA testing was performed in 54% (20/37), and all were ANCA negative by 18 months., Conclusions: Children with FRNS/SDNS on longer duration of levamisole were associated with increasing prevalence of ANCA positivity, but most of these children were clinically asymptomatic. Prospective studies are required to determine the chronology of ANCA positivity and its clinical implication., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Idiopathic nephrotic syndrome (INS) is the most common glomerular disease in children. We performed this study to report histopathological findings, the correlation between clinical and histopathological features, and the response to steroids and other immunosuppressive drugs and outcomes in Syrian children with INS., Methods: A single-center retrospective observational cohort study was conducted at Children's University Hospital in Damascus, and included all patients aged 1-14 years, admitted from January 2013 to December 2022, with INS and who underwent kidney biopsy., Results: The study included 109 patients, with a male/female ratio of 1.13:1, and a median age of 5 years with interquartile range (2.8-10). The main indication of kidney biopsy was steroid-resistant nephrotic syndrome (SRNS) (57.8%). The main histopathological patterns were minimal change disease (MCD) (45%) and focal segmental glomerulosclerosis (FSGS) (37.6%). FSGS was the most common histopathological pattern in SRNS (44.3%). In SRNS, we used calcineurin inhibitors to induce remission. Tacrolimus was used in 49 patients with response rate (complete remission of proteinuria) of 69.4% and cyclosporine in 20 patients with response rate of 50%. In steroid-dependent nephrotic syndrome (SDNS), we used mycophenolate mofetil (MMF) and cyclophosphamide to prevent relapses; MMF was used in 9 patients with response rate (maintaining sustained remission) of 89% and cyclophosphamide in 3 patients with response rate of 66.7%. Rituximab was used in four patients with FSGS, two SRNS patients and two SDNS patients, with sustained remission rate of 100%. Fifteen patients (13.7%) progressed to chronic kidney disease stage 5. Of them, 7 patients had FSGS and 8 patients had focal and global glomerulosclerosis;14 of them were steroid-resistant and one patient was steroid-dependent with persistent relapses. The most common outcome was sustained remission (47%) in MCD and frequent relapses (31.7%) in FSGS., Conclusions: FSGS was the most common histopathological pattern in idiopathic SRNS and had the worst prognosis. Calcineurin inhibitors could be an effective therapy to induce complete remission in SRNS. Rituximab may be an effective treatment to achieve sustained remission in SDNS and frequently relapsing NS and may have a potential role in SRNS with further studies required., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

CKD affects about 850 million people worldwide and is projected to be the fifth leading cause of death by 2040. Individuals from low- and middle-income countries (LMICs) bear the bulk of CKD. They face challenges including lack of awareness among the general population, as well as health care providers, unique risk factors such as genetic predispositions, infectious diseases, and environmental toxins, limited availability and affordability of diagnostic tests and medications, and limited access to KRTs. The inadequate health system infrastructure, human resources, and financing mechanisms to support comprehensive and integrated kidney care worsen the situation. Overcoming these challenges needs concerted efforts toward early detection, intervention, and multidisciplinary follow-up, policy, collaboration, advocacy, and financing. To achieve this, there is need for individual governments to include kidney health among the key health priorities and build capacity toward resilient health care systems. Integrating kidney care using the roadmaps of well-established management systems for other chronic diseases, such as HIV, has the potential to expedite the widespread adoption of kidney health. The aim of this article is to provide an overview of the current state and future prospects of kidney care in LMICs, highlighting the main challenges, ongoing efforts, and opportunities for improvement. We present case studies of exemplary efforts from three continents of the world with the highest densities of LMICs and propose potential strategies for a sustainable solution., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Introduction: For years, there has been an increase in the number of cases of chronic kidney disease (CKD) in human immunodeficiency virus (HIV)-infected patients. Renal dysfunction can be caused by direct effects of HIV on the kidneys but also of applied combined antiretroviral therapy (cART). Therefore there is a need of renal function diagnosis to monitor the development of kidney disturbances. In this study the urinary levels of selected low molecular weight proteins (LMWP) in HIV-infected patients were measured and related to current CD4+ T lymphocyte (LT CD4+) count, the glomerular filtration rate (eGFR) value and the applied cART. Material and methods: The levels of 5 LMWP -- kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), glutathione S-transferase α (GST-α) and π (GST-π) isoenzymes and neopterin (NPT) -- in urine were measured in HIV-infected patients and healthy controls by enzyme- linked immunosorbent assay. Results: Taking into account the current LT CD4+ count, KIM-1, NGAL and GST-α showed statistically significant differences between groups with the CD4+ count < 500 and ≥ 500 cells (< 0.001). Depending on the eGFR, apart from KIM-1 and NGAL, NPT showed statistically significant differences in the investigated groups with normal and lower eGFR values (< 0.001). In terms of applied cART, the best parameters in the assessment of kidney damage were NGAL, GST-π and NPT (< 0.001). Conclusions: This research shows that the analyzed LMWP parameters are useful in the assessment of kidney damage in HIV patients during cART, especially NPT, NGAL and GST-π. However, future studies should be conducted on larger groups. [ABSTRACT FROM AUTHOR]

Nephrotic syndrome (NS) is a common pediatric disease characterized by a dysfunction in the glomerular filtration barrier that leads to protein, fluid, and nutrient loss in urine. Corticosteroid therapy is the conventional treatment in children. Long-term complications of NS and prolonged exposure to steroids affect bones, growth, and the cardiovascular system. Diet can play an important role in preventing these complications, but there is a scarcity of scientific literature about nutritional recommendations for children with NS. They need individualized nutrition choices not only during the acute phase of the disease but also during remission to prevent the progression of kidney damage. The correct management of diet in these children requires a multidisciplinary approach that involves family pediatricians, pediatric nephrologists, dietitians, and parents. [ABSTRACT FROM AUTHOR]

Introduction: Kidney transplantation is a life-saving treatment for end-stage kidney disease (ESKD) patients. However, access to this treatment in Africa lags behind other regions, leading to significant disparities in care. We aimed to analyse the indications, demographics, and outcomes of kidney transplantation in Africa. Method: We conducted a systematic review of studies from PubMed, Google Scholar, and African Journal Online using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We pooled and analysed data on procedure type, graft outcomes, donor type, prophylaxis, post-operative complications, and survival from 33 eligible studies. Result: The most common causes of ESKD requiring transplantation were glomerulonephritis and nephroangiosclerosis. Open nephrectomy was the predominant surgical approach (95%). Living donors accounted for 56.3% (4221) of all donors, with 68.5% being related to the recipient. Cadaveric donors accounted for 43.7% (3280) of transplants. Graft rejection was the most common surgical complication (39.44%), and 60.49% of patients developed hypertension in the follow-up period. Conclusion: Our study highlights the potential of kidney transplantation to improve the lives of ESKD patients in Africa. However, further research and infrastructure development are necessary to make this treatment more widespread and successful. [ABSTRACT FROM AUTHOR]

Purpose of Review: Hepatitis B virus (HBV) infection is a global public health issue. While cirrhosis and hepatocellular carcinoma commonly affect patients with chronic HBV, extrahepatic manifestations are often unappreciated. Recent Findings: Extrahepatic manifestations can be variable in presentation but include several commonly described syndromes including HBV-related nephropathy, vasculitides, dermatitis, and arthritis. However, recently described entities include hematologic and neurologic manifestations. Summary: The primary immune-mediated mechanism common to many extrahepatic manifestations involves viral antigen-triggered immune complex formation. Initiation of antiviral treatment is associated with clinical response in most cases of extrahepatic disease; thus, recognition of these manifestations is essential to mitigating associated morbidity and mortality. [ABSTRACT FROM AUTHOR]

Purpose of Review: To review recent evidence on childhood hypertension across Africa, identifying knowledge gaps, challenges and priorities, and highlight clinical perspectives in managing primary hypertension. Recent Findings: Only 15 of the 54 African countries reported on absolute blood pressure (BP) measures, elevated BP, pre- and/or hypertension. The reported hypertension prevalence ranged between 0.0 and 38.9%, while elevated BP and/or pre-hypertnesion ranged from 2.7 to 50.5%. Childhood BP nomograms are lacking across Africa and the rates of hypertension were based on guidelines developed in countries with the lowest to no number of children from African ancestry. The recent studies across Africa also showed little to no detail when reporting BP specific methodology. No recent data informing the use or effectiveness of antihypertensive agents in children and adolesents are available. Summary: Childhood hypertension is on the rise, while data from Africa remains vastly under-represented. Collaborative research, resources, and policies need to be strengthened in addressing the growing public health concern of childhood onset hypertension on this continent. [ABSTRACT FROM AUTHOR]

Background: The pattern of paediatric kidney diseases across different regions is influenced by genetic, racial, and environmental differences. Objectives: The aim of this study was to review the current spectrum and outcome of childhood kidney diseases at Parirenyatwa Group of Hospitals and highlight the challenges of care. Design: Retrospective observational study. Methods: Data on all children below 16 years of age hospitalised for any kidney disease over an 8-month period (1 January-31 August 2022) were retrieved and retrospectively analysed. Kidney diseases were categorised as per standard definitions. Results: Kidney disease accounted for 2.2% (n = 50) of all 2264 admissions in the paediatric unit, with males constituting 60% (n = 30). Age ranged from 2 weeks to 13 years (mean 5.5 ± 3.5 years) with 58.0% being under 5 years. The commonest diagnoses in the unit were acute kidney injury (AKI) (n = 16, 32%) nephrotic syndrome (n = 16, 32%), hypertension (n = 12, 24%) and end stage kidney disease (ESKD) (n = 11, 22%) with some children presenting with more than 1 diagnosis. Only 3 out of 11 children with ESKD and 3 out of 8 children with AKI who required dialysis could be offered dialysis due to limited resources. Overall mortality rate was 32% (16/50): 5 children with AKI, 2 with nephrotic syndrome and normal kidney function, 8 with ESKD and 1 with Fanconi syndrome. Conclusion: Childhood kidney disease contributes significantly to hospitalisations at our institution with highest mortality among children with ESKD. The study highlighted the need for provision of essential drugs and kidney replacement therapy for children with kidney disease at our institution. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: Renal function can deteriorate in patients with chronic hepatitis B (CHB). We compared the risk of renal function decline between patients with untreated and treated CHB receiving antiviral therapy. Methods: This retrospective study included 1061 untreated CHB patients, and 366 on tenofovir alafenamide (TAF), 190 on besifovir dipivoxil maleate (BSV), and 2029 on entecavir (ETV). The primary outcome was renal function decline, a ≥ one‐stage increase in chronic kidney disease for ≥3 consecutive months. Results: The incidence and risk of renal function decline were significantly higher in the 1:1 propensity score‐matched treated group (588 pairs) than in the untreated (2.7 per 1000 person–years [PYs] vs. 1.3 per 1000 PYs, adjusted hazard ratio [aHR] = 2.29, all p < 0.001). The matched TAF group (222 pairs) showed a similar risk for the primary outcome (aHR = 1.89, p = 0.107) despite a significantly higher incidence thereof, compared to the untreated (3.9 vs. 1.9 per 1000 PYs, p = 0.042). The matched BSV and untreated groups (107 pairs) showed no significant differences in the incidence and risk. However, ETV users (541 pairs) carried a significantly higher outcome incidence and risk than the matched untreated (3.6 vs. 1.1 per 1000 PYs, aHR = 1.05, all p < 0.001). Compared to each matched untreated group, changes in the estimated glomerular filtration rate over time were greater in the ETV group (p = 0.010), despite being similar in the TAF (p = 0.073) and BSV groups (p = 0.926). Conclusions: Compared with untreated patients, TAF or BSV users showed similar risk, whereas ETV users showed a higher risk of renal function decline. [ABSTRACT FROM AUTHOR]

Background. Histopathological patterns of childhood primary nephrotic syndrome (PNS) and clinical response to steroids have been associated with certain race groups in parts of South Africa. However, there are no recent studies of childhood PNS in Cape Town. Objectives. To describe the demographics, histological subtypes and steroid response of patients with PNS who underwent kidney biopsies at Red Cross War Memorial Children's Hospital (RCWMCH) over a 10-year period. Methods. Details of patients with PNS who underwent kidney biopsies in the Paediatric Nephrology Department at RCWMCH between 2006 and 2015 were retrospectively recorded. Results. A total of 103 patients were included in the study. Most patients were either of mixed race (42%) or black (36%), with a mean age of 6.8 years and a male-to-female ratio of 1.19:1. The most identified histopathological subtype was mesangioproliferative glomerulonephritis (MesPGN; 60% (n/N=62/103)). Of the patients with focal segmental glomerulosclerosis (FSGS), MesPGN and minimal change disease (MCD) 45% (n/N=43/95) were steroid-resistant, and 54% (n/N=51/95) were steroid-sensitive. There was no significant association between any race group and steroid response. Patients with FSGS were more likely to be black, while MCD was more common in mixedrace patients (p=0.04). There was no difference in the likelihood of being mixed race or black between patients with FSGS and MesPGN (p=0.472). Conclusion. MesPGN was the most common histopathological subtype found in our study. There was no significant association between race and steroid response. Patients with FSGS were more likely to be black than mixed race when compared with MCD patients. Race was not otherwise significantly associated with any histopathological subtype. [ABSTRACT FROM AUTHOR]

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]

Aim: The earlier the onset of proteinuria, the higher the incidence of genetic forms. Therefore, we aimed to analyse the spectrum of monogenic proteinuria in Egyptian children presenting at age <2 years. Methods: The results of 27‐gene panel or whole‐exome sequencing were correlated with phenotype and treatment outcomes in 54 patients from 45 families. Results: Disease‐causing variants were identified in 29/45 (64.4%) families. Mutations often occurred in three podocytopathy genes: NPHS1, NPHS2 and PLCE1 (19 families). Some showed extrarenal manifestations. Additionally, mutations were detected in 10 other genes, including novel variants of OSGEP, SGPL1 and SYNPO2. COL4A variants phenocopied isolated steroid‐resistant nephrotic syndrome (2/29 families, 6.9%). NPHS2 M1L was the single most common genetic finding beyond the age of 3 months (4/18 families, 22.2%). Biopsy results did not correlate with genotypes (n = 30). On renin–angiotensin–aldosterone system antagonists alone, partial and complete remission occurred in 3/24 (12.5%) patients with monogenic proteinuria each, whereas 6.3% (1/16) achieved complete remission on immunosuppression. Conclusion: Genotyping is mandatory to avoid biopsies and immunosuppression when proteinuria presents at age <2 years. Even with such a presentation, COL4A genes should be included. NPHS2 M1L was prevalent in Egyptian children (4 months–2 years) with proteinuria, demonstrating precision diagnostic utility. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome occurring as a complication of immune tolerance therapy for inhibitors in hemophilia B is well recognized. It is also known to occur in association with factor borne infections, especially hepatitis C. This is the first case report of nephrotic syndrome occurring in a child receiving prophylactic factor VIII in the absence of inhibitors of hepatitis infection. However, the pathophysiology of this phenomenon is poorly understood. Case presentation: A 7-year Sri Lankan boy diagnosed with severe hemophilia A on weekly factor VIII prophylaxis was diagnosed with three episodes of nephrotic syndrome, a condition in which there is leakage of plasma protein into urine. He had three episodes of nephrotic syndrome, all of which responded well to 60 mg/m2 daily dose of oral steroids, achieving remission within 2 weeks of starting daily prednisolone. He has not developed inhibitors for factor VIII. His hepatitis screening remained negative. Conclusions: There is a possible link between factor therapy for hemophilia A and nephrotic syndrome, which can be a T-cell-mediated immune response. This case also highlights the importance of monitoring for renal involvement in patients treated with factor replacement. [ABSTRACT FROM AUTHOR]

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Glomerulonephritis (GN) is a predominant cause of kidney failure in Africa. The prevalence of primary GNs varies widely across Africa depending on the relative proportion of secondary GNs and genetic predispositions. We assessed the overall and subregional prevalence of primary GN and its histologic subtypes in Africa. We searched PubMed, EMBASE and African Journals Online for studies of biopsyproven primary GNs across all age groups in Africa published between 2010 and 2022. Data for primary GNs [minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), mesangioproliferative GN (MesPGN), membranoproliferative GN (MPGN), post-infectious GN (PIGN), IgA Nephropathy (IgAN), and crescentic GN (CresGN)] were extracted. Pooled prevalence was determined using the random effects model. Seventeen eligible articles (n = 6,494 individuals) from 8 African countries met the inclusion criteria. The overall pooled prevalence of FSGS, MCD, MN, MPGN, MesPGN, PIGN, IgAN and CresGN was 26.10%, 22.40%, 8.40%, 6.40%, 6.40%, 2.60%, 2.60%, 1.40%, respectively. Only 4 studies (23.5%) used light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM) for diagnosis. There were significant differences in the distribution of histologic subtypes in the paediatric compared to the adult population and across geographic sub-regions, with West Africa having a higher prevalence of FSGS. Overall, the dominance of FSGS across most regions and age groups has implications for disease diagnosis and ongoing care. Research efforts to understand the impact of this trend on kidney disease outcomes and efforts to improve kidney biopsy practice as a means of early disease detection are needed in Africa. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) is a lentivirus that is transmissible through blood and other body fluids. During the late 1980s and early 1990s, an estimated 10,000 Romanian children were infected with HIV-1 subtype F nosocomially through contaminated needles and untested blood transfusions. Romania was a special case in the global acquired immunodeficiency syndrome (AIDS) pandemic, displaying the largest population of HIV-infected children by parental transmission between 1987–1990. In total, 205 HIV-infected patients from the western part of Romania were analyzed in this retrospective study. Over 70% of them had experienced horizontal transmission from an unknown source, while vertical transmission was identified in only five cases. Most patients had a moderate to severe clinical manifestation of HIV infection, 77.56% had undergone antiretroviral (ARV) treatment, most of them (71.21%) had experienced no adverse reactions and many of those with HIV (90.73%) had an undetectable viral load. Renal impairment was detected in one third of patients (34.63%). Patients born before 1990, male patients, patients diagnosed with HIV before the age of 10, and those undernourished or with renal impairment had a shorter average survival time than the group born after 1990, female patients, patients receiving ARV treatment, patients with a normal body mass index (BMI) and those without renal impairment. Periodical monitoring of the estimated glomerular filtration rate (eGFR) level, as well as the detection of protein excretion, should be taken into consideration worldwide when monitoring HIV-positive patients; this in order to detect even asymptomatic chronic kidney disease (CKD), and to manage these patients and prolong their lives. [ABSTRACT FROM AUTHOR]

Background: Acute post-streptococcal glomerulonephritis (APSGN) is a common cause of acute kidney injury (AKI) in children; however, in a small subgroup, the presentation is one of rapidly progressive glomerulonephritis (RPGN) deteriorating kidney function associated with severe oligo-anuria or a mixed nephritic-nephrotic picture. This study reviewed potential clinical and laboratory factors which may assist the treating clinician to identify patients at high risk of severe disease., Methods: All kidney biopsies for APSGN performed between 1996 and 2020 were obtained from a departmental biopsy database. Clinical and laboratory data were extracted from the patients' clinical records. Kidney biopsies were reviewed and scored independently by a renal histopathologist., Results: Thirty of 53 (56.6%) patients had stage 3 AKI at initial presentation with a median estimated glomerular filtration rate (eGFR) 27 (IQR 11-41), falling to 20 ml/min/1.73 m 2 (IQR 13.3-43) at time of biopsy. Patients who had either a pre-biopsy eGFR < 35 ml/min/1.73 m 2 or a ≥ 25% fall in eGFR between admission and biopsy were more likely to have glomerular crescents (p = 0.004). Multivariate regression analysis and receiver operating curve showed the pre-biopsy eGFR most accurately predicted glomerular crescents (p = 0.047, ROC 0.757). There were no significant predictors of nephrotic proteinuria or nephrotic syndrome during the acute phase., Conclusions: Severe APSGN is associated with a pronounced reduction in eGFR. Calculation of eGFR in this small group of patients may assist in identifying which patient should have an urgent kidney biopsy to facilitate a more accurate clinical diagnosis and management plan., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Purpose: The objective of this systematic review was to determine a minimum serum 25-hydroxyvitamin D (25OHD) threshold based on the risk of having rickets in young children. This work was commissioned by the WHO and FAO within the framework of the update of the vitamin D requirements for children 0-3 years old., Methods: A systematic search of Embase was conducted to identify studies involving children below  4 years of age with serum 25OHD levels and radiologically confirmed rickets, without any restriction related to the geographical location or language. Study-level and individual participant data (IPD)-level random effects multi-level meta-analyses were conducted. The odds, sensitivity and specificity for rickets at different serum 25OHD thresholds were calculated for all children as well as for children with adequate calcium intakes only., Results: A total of 120 studies with 5412 participants were included. At the study-level, children with rickets had a mean serum 25OHD of 23 nmol/L (95% CI 19-27). At the IPD level, children with rickets had a median and mean serum 25OHD of 23 and 29 nmol/L, respectively. More than half (55%) of the children with rickets had serum 25OHD below 25 nmol/L, 62% below 30 nmol/L, and 79% below 40 nmol/L. Analysis of odds, sensitivities and specificities for nutritional rickets at different serum 25OHD thresholds suggested a minimal risk threshold of around 28 nmol/L for children with adequate calcium intakes and 40 nmol/L for children with low calcium intakes., Conclusion: This systematic review and IPD meta-analysis suggests that from a public health perspective and to inform the development of dietary requirements for vitamin D, a minimum serum 25OHD threshold of around 28 nmol/L and above would represent a low risk of nutritional rickets for the majority of children with an adequate calcium intake., (© 2024. The Author(s).)

Therapeutic options with immunosuppressive agents for glomerular diseases have widened with refinements to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines from 2012 to 2021. However, international guidelines do not necessarily match the reality in each country. Expensive therapies such as rituximab and calcineurin inhibitors are sometimes inaccessible to patients with refractory nephrotic syndrome due to cost or regulations. Under the Japanese medical insurance system, rituximab is accessible but still limited to steroid-dependent patients who developed idiopathic nephrotic syndrome in childhood. Based on international KDIGO guidelines and other national guidelines, possible applications of immunosuppressive agents for nephrotic syndrome are comprehensively examined in this review. While rituximab has become the mainstay of immunosuppressive therapy for nephrotic syndrome, clinical trials have indicated that options such as cyclophosphamide, calcineurin inhibitors, and mycophenolate mofetil would be preferable. Given the rising number of patients with nephrotic syndrome worldwide, KDIGO guidelines mention the need for further consideration of cost-effectiveness. If the new option of rituximab is to be the first choice in combination with steroids for nephrotic syndrome, its cost-effectiveness should also be verified. Among the few studies examining the cost-effectiveness of treatments for nephrotic syndrome, administration of rituximab to young adults has been shown to be cost-beneficial, at least in Japan. However, further large-scale studies involving multiple facilities are needed to verify such findings. Network meta-analyses have concluded that the efficacy of rituximab remains controversial and confirmation through high-quality studies of large cohorts is needed. To this end, the mechanisms of action underlying immunosuppressive agents, both old and new, need to be understood and experience must be accumulated to evaluate possible effects and side effects. [ABSTRACT FROM AUTHOR]

Background: The ease of access to antiretroviral therapy (ART) has improved both survival rate and comorbidities in patients with human immunodeficiency virus (HIV) infection. Impaired kidney function is one of the most common comorbidities of HIV. CD4 and viral load can be used to monitor HIV progression and to determine the effectiveness of ART. The most commonly used estimated-glomerular filtration rate (e-GFR) technique is to use serum creatinine but often causes late detection of kidney dysfunction while serum cystatin increases at the beginning of the GFR decrease. This supports cystatin C serum as an early diagnostic tool to detect kidney function or biomarker early kidney disorders. Objective: To evaluate a possible association between serum cystatin C as a marker of kidney function and HIV progression through CD4 levels and viral load. Methods: This cross-sectional study was conducted through evaluation of secondary data from medical and laboratory records of pediatric patients who had routine visits to the HIV Clinic at Dr. Hasan Sadikin General Hospital, Bandung, West Java, in January-February 2020. Results: Sixty subjects were reviewed in the study. Median cystatin C-based eGFR was 28.1mL/minute/1.73m². Subjects were categorized by viral load result into <40 and ≥40 copies/mL. The median serum cystatin C was significantly higher [3.7 (range 2.61-6.55) mg/L] in the >40 copies/mL viral load group than the <40 copies/mL group [2.4 (range 0.26-13.61) mg/L]. The median absolute CD4 count, CD4 percentage, and cystatin C were 776 (range 7-1644) cells/mm3, 27.5 (range 1.6-57.4) %, and 3 (range 0.26-13.61) mg/L, respectively. There were no significant correlations (r=-0.2; P=0.1) between CD4 and serum cystatin C Conclusion Higher viral load associates with higher cystatin C level, while CD4 shows no correlation to cystatin C. However, patients with low CD4 tend to have increased cystatin C level. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Hepatology / Linchuang Gandanbing Zazhi is the property of Journal of Clinical Hepatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The prokaryotic, viral, fungal, and parasitic microbiome exists in a highly intricate connection with the human host. In addition to eukaryotic viruses, due to the existence of various host bacteria, phages are widely spread throughout the human body. However, it is now evident that some viral community states, as opposed to others, are indicative of health and might be linked to undesirable outcomes for the human host. Members of the virome may collaborate with the human host to retain mutualistic functions in preserving human health. Evolutionary theories contend that a particular microbe's ubiquitous existence may signify a successful partnership with the host. In this Review, we present a survey of the field's work on the human virome and highlight the role of viruses in health and disease and the relationship of the virobiota with immune system control. Moreover, we will analyze virus involvement in glomerulonephritis and in IgA nephropathy, theorizing the molecular mechanisms that may be responsible for the crosslink with these renal diseases. [ABSTRACT FROM AUTHOR]

Introduction: HIV is a chronic viral infection documented worldwide. It infects and destroys helper T cells (CD4), leading to a number of immunological deficiencies. The main objective of this study was to examine the rheumatoid factor (Rf) to recognize the rheumatoid arthritis prevalence rate in HIV-infected patients. Material and methods: This hospital-based cross-sectional study was carried out among 150 HIVpositive individuals visiting ART center of Western Regional Hospital. Patients were counseled, and samples were taken. Samples were processed by MISPA-i2 and analyzed using SPSS. Rf was measured for all participants. Results: Out of the 150 participants, 35 (23.3%) were Rf-positive for rheumatoid arthritis. In multivariable analysis, these levels were higher in 20-40 years age group, females, married, illiterate, and unknown about their HIV transmission. The prevalence of rheumatoid arthritis was observed in 23.3% of participants. Similarly, the association of sex and other variables significant values were found in education, mode of transmission, and age categories, as 0.004, 0.001, and 0.001, respectively. Conclusions: The results of our research suggest the need for regular screening for Rf among HIVpositive patients in order to reduce mortality and pain in these individuals due to rheumatoid arthritis. [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]