Epigenetic mechanisms and steroid-resistant nephrotic syndrome: The future potential for SRNS diagnosis

Nephrotic syndrome (NS) is commonly managed with glucocorticoid (GC) therapy, yet about 10%-30% of children do not achieve remission after an adequate initial steroid course and are classified as steroid-resistant nephrotic syndrome (SRNS); in adults, proportions are generally higher and heterogeneous across histologies. Currently, genetic testing can identify causative mutations in 30% of SRNS cases, highlighting the need for complementary pre-treatment stratification approaches. This review synthesizes human evidence linking epigenetic dysregulation to GC responsiveness, highlighting differential DNA methylation patterns in genes such as NLRP3 and SOCS3. Simultaneously, the expression levels of microRNAs (miRNAs) such as miR-142 and miR-30 have been shown to be associated with the efficacy of GC treatment. We propose a multi-biomarker integrative analysis strategy that combines methylation profiles with miRNA expression and emerging histone modification signals for pre-treatment risk stratification and prediction of therapeutic response, thereby reducing ineffective steroid exposure and enabling mechanism-informed management pending prospective validation.