Circulating miRNA-377 as an Epigenetic Regulator and Diagnostic Biomarker in the Early Detection and Progression of Diabetic Nephropathy: A Cross-Sectional Analytical Study.

BACKGROUND: Diabetic nephropathy (DN) is a leading microvascular complication of diabetes and a major cause of end-stage renal disease. Conventional biomarkers such as albuminuria fail to detect early renal injury. MicroRNA-377 (miRNA-377) has emerged as a potential epigenetic regulator involved in renal fibrosis and extracellular matrix accumulation. AIM: To evaluate circulating miRNA-377 expression across different stages of DN and determine its diagnostic utility. METHODS: This analytical cross-sectional study included 132 participants categorized into healthy controls (n = 35), type 2 diabetes mellitus (T2DM) with normoalbuminuria (n = 32), microalbuminuria (n = 32), and macroalbuminuria (n = 33). Plasma miRNA-377 expression was quantified using reverse transcription polymerase chain reaction (RT-PCR) and analyzed by the Livak method. Clinical, biochemical, and renal parameters were assessed. Statistical analysis included ANOVA, Spearman correlation, receiver operating characteristic (ROC) curve, and multinomial regression. RESULTS: miRNA-377 expression showed significant upregulation in microalbuminuria (P = 0.022) and macroalbuminuria (P = 0.014). It demonstrated strong correlation with urinary albumin-to-creatinine ratio (UACR) (r = 0.510, P < 0.001) and moderate correlation with HbA1c (P = 0.04). ROC analysis showed good diagnostic performance (area under the curve [AUC] =0.811). Multinomial regression confirmed miRNA-377 as an independent predictor of DN progression. CONCLUSION: Circulating miRNA-377 is significantly associated with DN severity and may serve as a promising non-invasive biomarker for early detection and disease stratification.