Nephrotic Syndrome Management in Pediatric Populations

Nephrotic syndrome in children is a chronic glomerular disorder marked by heavy proteinuria, hypoalbuminaemia and oedema, with a global incidence of 1–17 cases per 100 000 children. Initial management centres on glucocorticoid therapy, achieving remission in most steroid-sensitive cases. However, frequent relapsing or steroid-dependent patients face cumulative steroid toxicity and often require steroid-sparing immunosuppressive agents such as calcineurin inhibitors, anti-CD20 antibodies and antiparasitic immunomodulators. A subset exhibits steroid resistance, prompting genetic evaluation and tailored regimens to delay progression to end-stage kidney disease. Beyond immunotherapy, supportive strategies addressing oedema, thrombosis and infection risk are integral. Advances in genomics, pharmacogenetics and clinical trials are refining risk stratification and guiding individualised treatment protocols worldwide.

Research from Nature Portfolio

Recent studies have performed a multi-population genome-wide association analysis in over 38 000 participants, identifying twelve significant risk loci for paediatric steroid-sensitive nephrotic syndrome. Fine-mapping in the HLA Class II region has pinpointed specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 that drive genetic susceptibility, while non-HLA loci colocalise with expression quantitative trait loci in monocytes and T-cell subsets. Overlap with open chromatin regions in kidney cells suggests uncharacterised intrarenal mechanisms. Moreover, a polygenic risk score derived from these variants correlates with earlier disease onset and may predict relapse likelihood. These discoveries broaden understanding of the molecular drivers of disease and pave the way for cell-specific therapies and precision medicine approaches.

Nephrotic Syndrome Management in Pediatric Populations publication trend

The graph below shows the total number of articles in nephrotic syndrome management in pediatric populations across all publications each year (not limited to Nature Index journals).

Technical terms

Steroid-sensitive nephrotic syndrome: A form of paediatric nephrotic syndrome that achieves complete remission of proteinuria following standard glucocorticoid therapy.

Steroid-resistant nephrotic syndrome: Persistent proteinuria despite an adequate course of glucocorticoid treatment, often requiring alternative immunosuppressive strategies and genetic assessment.

Genome-wide association study (GWAS): A method to scan the genome for common genetic variants in large populations to identify those associated with disease risk.

Polygenic risk score: A composite measure of genetic susceptibility calculated by summing risk alleles weighted by their effect sizes.

HLA Class II region: A genomic locus encoding antigen-presenting molecules that influence immune responses and are frequently implicated in autoimmune and immune-mediated diseases.

Immunosuppressive therapy: Treatment employing drugs that reduce or modulate immune activity to induce remission and prevent relapse of nephrotic syndrome.

References

1. Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome. Nature Communications (2023).
2. A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort. Genes & Diseases (2023).
3. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome. Pediatric Nephrology (2020).
4. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome. Pediatric Nephrology (2022).
5. Incidence of remission and relapse of proteinuria, end-stage kidney disease, mortality, and major outcomes in primary nephrotic syndrome: the Japan Nephrotic Syndrome Cohort Study (JNSCS). Clinical and Experimental Nephrology (2020).