Prediction of biomarkers for steroid resistance in patients with nephrotic syndrome

Background. Glucocorticoids (GCs) are the primary therapy for idiopathic nephrotic syndrome (iNS). However, reliable indicators for predicting steroid-resistant nephrotic syndrome (SRNS) remain insufficiently established. Objective. This study aimed to identify urinary, circulating, and molecular biomarkers capable of predicting SRNS in adult patients with iNS. Methods. A total of 140 adult patients (aged 21–55 years) with iNS were enrolled, including 65 (46%) with SRNS and the remainder with steroid-sensitive nephrotic syndrome (SSNS). Urinary biomarkers (urine protein and urine albumin creatinine ratio [uACR]), circulating serum biomarkers (suPAR, MCP-1, IP-10, and NGAL), and molecular biomarkers (Caspase-3 and CD2AP) were analyzed using ELISA and qPCR techniques. Results. Urinary biomarkers (uACR and urine protein) significantly differed between SRNS and SSNS groups. Among iNS subtypes, focal segmental glomerulosclerosis (FSGS) was the most frequent in both groups. Among circulating biomarkers, only suPAR and NGAL showed significant differences (p < 0.05) between SRNS and SSNS. ROC-AUC analysis indicated that urine biomarkers had higher sensitivity, specificity, predictive values, and accuracy compared to serological biomarkers. Gene expression of CASPASE-3 and CD2AP was elevated in SRNS patients relative to healthy controls. Conclusions. Urine biomarkers demonstrate superior sensitivity and specificity in predicting SRNS in adult iNS patients. A combined biomarker panel could improve diagnostic accuracy. FSGS was the most common iNS subtype and correlated strongly with suPAR levels. Elevated expression of molecular biomarkers in SRNS suggests their potential role as diagnostic tools, warranting further investigation.