Urinary Netrin-1 as an early marker of tubular injury in type 2 diabetes mellitus: correlation with glycemic control and albuminuria

Abstract Background Diabetic nephropathy (DN) remains a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Tubular biomarkers, such as urinary Netrin-1, are emerging as early indicators of renal damage in diabetes, preceding albuminuria. Objective To assess urinary Netrin-1 levels in patients with type 2 diabetes mellitus (T2DM) and investigate its association with glycemic control and albuminuria status. Methods This case–control study included 120 participants recruited from Kasr Al-Ainy endocrinology clinics. Ninety T2DM patients were stratified into three subgroups: normoalbuminuria, microalbuminuria, and macroalbuminuria (30 patients each), and compared to 30 healthy controls. Clinical, biochemical, and urinary parameters including fasting blood glucose (FBG), 2-h postprandial glucose (2hPG), HbA1c, lipid profile, creatinine, eGFR, and urinary Netrin-1 were assessed. Results Urinary Netrin-1 levels were significantly elevated in diabetic patients compared to controls (p < 0.001) and showed a stepwise increase across the normo-, micro-, and macroalbuminuria subgroups. Netrin-1 levels positively correlated with FBG, 2hPG, HbA1c, total cholesterol, LDL, systolic blood pressure, and albumin/creatinine ratio. ROC analysis identified a urinary Netrin-1 cutoff of ≥ 391.5 pg/mg with 56.7% sensitivity and 96.7% specificity for detecting DN. Conclusion Urinary Netrin-1 is significantly elevated in T2DM patients and correlates with both glycemic control and degree of albuminuria. It may serve as a sensitive non-invasive biomarker for early tubular injury and disease progression in diabetic nephropathy.