Dysregulation of serum miR-221 and miR-18 in pediatric idiopathic nephrotic syndrome: a case-control study

Idiopathic nephrotic syndrome (INS) is a common and challenging glomerular disease in children. Noninvasive biomarkers are needed to improve diagnosis and understand its pathophysiology. This study aimed to investigate the serum expression profiles of the inflammation-associated miR-221 and miR-18 in children with INS. Fifty children with an INS diagnosis and 50 healthy controls were included. Venous blood samples were collected, and serum expression levels of miR-221 and miR-18 were quantified using qRT-PCR. Statistical analysis was performed using non-parametric tests. Serum levels of both miR-221 (Median = 1.96, IQR: 0.69–5.17) and miR-18 (Median = 2.9, IQR: 0.96–13.36) were significantly upregulated in children with INS compared to controls (p < 0.001 and p = 0.011, respectively). A strong positive correlation was observed between the two miRNAs (rs = 0.778, p < 0.0001). Multivariate logistic regression revealed that miR-18 remained a significant independent predictor of INS when adjusting for body weight (OR = 4.618, p = 0.049), whereas miR-221 did not. In ROC analysis, individual AUCs were 0.72 for miR-18 and 0.64 for miR-221. Notably, a combined miRNA panel (miR-18 + miR-221) demonstrated superior diagnostic accuracy with an AUC of 0.80 (95% CI: 0.64–0.96), yielding 80% sensitivity and 100% specificity. No significant difference in expression was found between steroid-sensitive and steroid-resistant subgroups (p > 0.05). Serum miR-18 and miR-221 are associated with pediatric INS, with miR-18 acting as a robust independent predictor. The diagnostic potential of these miRNAs is significantly enhanced when utilized as a combined panel, providing a promising noninvasive signature for the disease.