Beyond the Steroid Trial: A Scoping Review of Biomarkers for Pediatric Nephrotic Syndrome

Background: Pediatric idiopathic nephrotic syndrome (INS) is classified primarily by corticosteroid response, delaying identification of steroid-resistant disease and exposing children to unnecessary treatment toxicity. Novel biomarkers could enable earlier biological stratification and treatment guidance. Objectives: The study aimed to map available evidence on candidate biomarkers in pediatric INS published since 2020, with emphasis on anti-nephrin autoantibodies and their potential for clinical translation. Data Sources: PubMed/MEDLINE and Web of Science Core Collection (January 2020-October 2025), with a supplementary verification search in Scopus and Embase and manual reference screening. Eligibility Criteria: Original studies reporting circulating, urinary, or tissue-based biomarkers in children aged 0-18 years with idiopathic NS, with outcomes related to diagnosis, treatment response, relapse prediction, or monitoring. Studies in adults only, secondary NS, or animal models were excluded. Results: After screening, 34 studies met the eligibility criteria and were included, grouped into five categories: autoantibodies, urinary markers, immune cell signatures, cytokines/chemokines, and exploratory markers (metabolomics, extracellular vesicles, lipid profiles, microRNAs). Anti-nephrin IgG emerged as the most mechanistically informative marker, with seroprevalence declining across phenotypes (SSNS 68%, SDNS 28%, non-genetic SRNS 14%, genetic SRNS 2%) and positivity predicting response to intensified immunosuppression. Of the candidates reviewed, urinary NGAL and peripheral B-cell subset monitoring are the most readily implementable with existing laboratory infrastructure. Conclusions: Pediatric INS encompasses a spectrum of immune-mediated podocytopathies that may soon be distinguishable by emerging biomarker profiles. Anti-nephrin autoantibodies provide the strongest mechanistic evidence for an autoimmune podocytopathy.