miR-135a-5p in Exosomes Promotes Childhood Nephrotic Syndrome via GSK-3β and TGF-β1 Crosstalk

Background Nephrotic syndrome (NS) is an autoimmune kidney disorder that is characterized by severe protein loss in urine, which results in edema, hyperlipidemia, and hypoalbuminemia. Glucocorticoid therapy is the main treatment for NS patients; however, the unsuitable treatment of NS can lead to chronic glomerulonephritis and, in turn, end-stage renal disease (ESRD). Genetic and epigenetic variations between individuals lead to different responses to treatment. Therefore, this study aimed to investigate an early predictor for glucocorticoid response in NS patients. Therefore, this study aimed to investigate an early predictor for glucocorticoid response in NS patients. Methods This study was conducted on 70 NS patients enrolled from the Nephrology Unit of Mansoura University Children’s Hospital and 70 aberrantly healthy individuals as a control group. Peripheral blood samples were collected from all subjects for miR-135a-5p, GSK3β, and TGFB-1 expression. Results miR-135a-5p level was significantly decreased, while the GSK3β and TGFB-1 expression levels were increased in the NS group compared to the control group. Regarding the NS subtypes, the steroid-resistant nephrotic syndrome (SRNS) group exhibits a significant reduction in miR-135a-5p and a significant elevation in the levels of GSK3β and TGFB-1 compared to the steroid-sensitive nephrotic syndrome (SSNS) group. Conclusion These biomarkers demonstrated moderate diagnostic accuracy in distinguishing nephrotic syndrome (NS) from controls and effectively identified steroid-resistant NS (SRNS) cases. Their potential as early predictors of glucocorticoid response offers promising clinical utility for personalized therapeutic strategies in pediatric NS.