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 <i>NLRP3</i> and <i>SOCS3</i>. 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.