Integrative Molecular Stratification of Steroid Response in Childhood Nephrotic Syndrome

Abstract

BACKGROUND AND AIM: Nephrotic syndrome (NS) is a glomerular disorder, with significant morbidity globally. Given the challenge of glucocorticoid resistance, this study aimed to evaluate actionable genetic and epigenetic biomarkers to enable early prediction of therapeutic response. SUBJECTS AND METHODS: This study comprised 70 pediatric NS patients enrolled from Mansoura University Children's Hospital's Nephrology Department, compared to 70 apparently healthy children of the same sex and age distribution (control group). RT-PCR was conducted for all subjects for determination of exosomal (miR-331-3p, miR-486-3p), and MAP2K7 expression. RESULTS: RT-PCR results showed a significant reduction in exosomal (miR-331-3p and miR-486-3p) expression levels, and MAP2K7 in the NS group against control. Additionally, in particular, a significant decrease in steroid-resistant nephrotic syndrome (SRNS) compared to the other NS subtypes was observed. These markers have proved a discriminating ability to differentiate NS patients from controls and to predict susceptibility of SRNS. CONCLUSION: The identified markers exosomal (miR-331-3p and miR-486-3p) represented a moderate level of diagnostic accuracy in differentiating between NS patients and controls, with particular efficacy of exosomal miR-331-3p in segregating SRNS cases. These findings suggest potential utility as early predictive biomarkers for glucocorticoid treatment response.