Novel mutation patterns in children with steroid-resistant nephrotic syndrome

Background Idiopathic Nephrotic Syndrome (NS) in children poses treatment challenges, with a subset developing Steroid-Resistant Nephrotic Syndrome (SRNS). Genetic factors play a role, yet data on pediatric SRNS genetics in India are scarce. We conducted a prospective study utilising whole-exome sequencing to explore genetic variants and their clinical correlations. Methods A single-centre prospective study (October 2018–April 2023) enrolled children with SRNS, undergoing renal biopsy and genetic testing per institutional protocol. Clinical, histological, and genetic data were recorded. DNA isolation and next-generation sequencing were conducted for genetic analysis. Data collection included demographics, clinical parameters, and kidney biopsy findings. Syndromic features were evaluated, with second-line immunosuppressive therapy administered. Patient and renal outcomes are presented for patients with and without genetic variants. Results A total of 680 pediatric NS patients were analysed, with 121 (17.8%) having SRNS and 96 consent to genetic analysis. 69 (71.9%) had early SRNS, 27 (28.1%) late. Among participants, 62 (64.56%) had reportable genetic variants. The most common were in COL4A genes, with 20 (31.7%) positive. Renal biopsy showed FSGS in 31/42 (74%) with variants, 16/28 (57.1%) without variants. Second-line immunosuppressions varied, with CNIs most common. Outcomes varied, with partial or complete remission achieved in some while others progressed to ESRD. Conclusion The study underscores the importance of genetic analysis in pediatric SRNS, revealing variants in 65.7% of cases. COL4A variants were predominant. Variants correlated with varied renal outcomes, highlighting potential prognostic implications. These findings emphasise the value of personalised approaches and further research in managing pediatric SRNS.