Kidney outcomes in children with primary focal segmental glomerulosclerosis from a low- and middle- income country.

BACKGROUND: Limited data exists regarding the clinical course and outcomes of children with primary focal segmental glomerulosclerosis (FSGS) from low- and middle- income countries. METHODS: Children aged 1-18 years with biopsy-proven primary FSGS followed from January 2010-June 2023 in a tertiary-care center were enrolled and their clinical profile, histological characteristics, kidney outcomes, and predictors of adverse outcomes were determined. RESULTS: Over 13 years, 73 (54.8% boys) children with median (IQR) age at FSGS diagnosis 6.7 (3,10) years were recruited and followed up for median 4 (2.5,8) years. FSGS-not otherwise specified (NOS) was the most common histological subtype, in 64 (87.6%) children, followed by collapsing variant in 5 (6.8%) children. At last follow-up, 43 (58.9%), 2 (2.7%) and 28 (38.3%) children were in complete remission (CR), partial remission (PR), and no remission (NR) respectively. Calcineurin inhibitors led to CR or PR in 39 (62%) children. Overall, 21 (28.7%) children progressed to chronic kidney disease (CKD) stage 2-5 (19 from NR vs. 2 from PR group; p = 0.03); with 41% of those NR at 12 months progressing to CKD 4-5 by last follow-up. On multivariable analysis, collapsing variant [adjusted HR 2.5 (95%CI 1.5, 4.17), p = 0.001] and segmental sclerosis > 25% [aHR 9.9 (95%CI 2.2, 45.2), p = 0.003] predicted kidney disease progression. CONCLUSIONS: In children with FSGS, response to immunosuppression predicts kidney survival as evidenced by nil to lower progression to CKD 2-5 by median follow-up of 4 (2.5,8) years in children with CR and PR, compared to those with no remission at 12 months from diagnosis. Segmental sclerosis > 25% and collapsing variant predicted progression to advanced CKD.

Clinical characteristics and genetic profile of children with WDR72-associated distal renal tubular acidosis: a nationwide experience.

BACKGROUND: Limited data, primarily from small case series, exist regarding the clinical profile, genetic variants, and outcomes of WDR72-associated distal renal tubular acidosis (WDR72-dRTA). METHODS: Our study enrolled children diagnosed with WDR72-dRTA below 18 years of age from 9 Indian centers and analyzed their clinical characteristics, genetic profiles, and outcomes. Potential genotype-phenotype correlations were explored. RESULTS: We report 22 patients (59% female) with WDR72-dRTA who were diagnosed at a median age of 5.3 (3, 8) years with polyuria (n = 17; 77.3%), poor growth (16; 72.7%), and rickets (9; 40.9%). Amelogenesis imperfecta was present in 21 (95.5%) cases. At presentation, all patients had normal anion gap metabolic acidosis; hypokalemia and nephrocalcinosis were seen in 17 (77.3%) patients each. Seven (31.8%) patients had concomitant proximal tubular dysfunction. Genetic analysis identified biallelic nonsense variants in 18 (81.8%) patients, including novel variants in 6 cases. A previously reported variant, c.88C > T, and a novel variant, c.655C > T, were the most frequent variants, accounting for 10 (45.5%) cases. Over a median follow-up of 1.3 (1, 8) years, the height velocity improved by 0.74 (0.2, 1.2) standard deviation scores, while 3 children (13.6%) progressed to chronic kidney disease (CKD) stage 2, with eGFR ranging from 67 to 76 mL/min/1.73 m2, respectively, after 11.3-16 years of follow-up. No specific genotype-phenotype correlation could be established. CONCLUSIONS: WDR72-dRTA should be considered in children with typical features of amelogenesis imperfecta and dRTA. Biallelic nonsense variants are common in Asians. While most patients respond well to treatment with improved growth and preserved eGFR, on long-term follow-up, a decline in eGFR may occur.

The Assisted Reproductive Technology Act 2021- Provisions and Implications.

The desire for parenthood among infertile individuals is often fulfilled by resorting to the ever-evolving Assisted Reproductive Techniques (ART). Since the birth of Durga, India's first baby born using ART in 1981, the lucrative fertility industry has grown exponentially in our country. The Government of India passed the Assisted Reproductive Technology (Regulatory) Act in 2021 to provide regulatory support to these services. The legislation offers clarity on various aspects of ART, including measures to safeguard children born through these procedures. The effective implementation of the ART Act is crucial to ensure that ART services become affordable, ethical, and socially acceptable in India. This article aims to discuss the controversies with ART services and issues that could compromise the wellbeing of children, while highlighting the provisions provided under the Act to address these.

Clinical Profile and Outcomes of Children with Acute Liver Failure in a Tertiary Care Center in South India: A Retrospective Study.

Purpose: In this study, we investigated the clinical profile, survival at discharge, and proportion of children with acute liver failure (ALF) meeting the criteria for, yet surviving without, liver transplantation (LT). Methods: Medical case records of children aged >28 days to ≤15 years over a period of 7 years, identified from pediatric admission and discharge registers, were screened. Children satisfying the criteria for ALF were included in this study. Results: A total of 71 records meeting the pediatric ALF (PALF) criteria were included. The survival rate at discharge was 61% (n=44). A considerable proportion of children satisfied the King's College Criteria (KCC) (56.3%) and the European Association for the Study of the Liver (EASL) criteria (7%) for LT at admission. Nonetheless, the survival rate in the absence of LT was 42.5% in children who satisfied the KCC and 20% in those who met the EASL criteria. Infection (29.5%) and paracetamol overdose (19.7%) were the major identifiable causes of PALF. Hepatitis A was the most common infection identified. No significant predictors of poor outcomes were identified in multivariable analysis. Conclusion: Our study highlights the changing survival rates and the clinical and etiological profiles of patients with PALF. In areas with poor access to LT services, survival in these children could be improved through early referral to centers with adequate intensive care facilities. Preventing ALF and referring patients to LT services are paramount to reducing mortality.

Genetic Studies in Infants with Congenital Nephrotic Syndrome: A Case Series.

Information on the genetic profile of congenital nephrotic syndrome (CNS) from India is scarce. The management of CNS is largely supportive of the setting of developing countries, mainly via the administration of intravenous albumin infusions, angiotensin-converting enzyme inhibitors, and levothyroxine. Inadequate infrastructure and management facilities, including genetic analyses, further hamper the outcome. These infants may progress to end-stage renal disease, and mortality is high in infancy. Here, we report a case series of four infants (aged 14-60 days) with CNS from our center with genetic mutations (including mutations in the NPHS1 and LAMB2 genes) that were not described in previous reports from India. Although responsiveness to enalapril has been documented in anecdotal reports of NPHS1 mutations, our case series of four infants did not exhibit any response to enalapril. Our case series adds to the existing literature regarding the genetic profile of CNS in India.

Vitamin D-dependent rickets (VDDR) type 1: case series of two siblings with a CYP27B1 mutation and review of the literature / Raquitismo dependente de vitamina D: tipo 1: série de casos de dois irmãos com mutação CYP27B1 e revisão da literatura

Abstract Two siblings presented with clinical and biochemical features of rickets, initially suspected as hypophosphatemic rickets. There was no improvement initially, hence the siblings were reinvestigated and later diagnosed as having vitamin D-dependent rickets (VDDR) type 1 due to a rare mutation in the CYP27B1 gene encoding the 1α-hydroxylase enzyme. Both siblings improved with calcitriol supplementation. The initial presentation of VDDR is often confusing and algorithmic evaluation helps in diagnosis. We also present a brief review of the literature, including genetics.

Resumo Dois irmãos apresentaram características clínicas e bioquímicas do raquitismo, com suspeita clínica inicial de raquitismo hipofosfatêmico. Não houve melhora no início, portanto os irmãos foram reavaliados e, posteriormente, diagnosticados com raquitismo dependente de vitamina D (VDDR) tipo 1 devido a uma rara mutação no gene CYP27B1, que codifica a enzima 1a-hidroxilase. Ambos os irmãos melhoraram com a suplementação de calcitriol. A apresentação inicial do VDDR geralmente é confusa e a avaliação algorítmica ajuda no diagnóstico. Também apresentamos uma breve revisão da literatura, incluindo genética.