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.