Urinary neutrophil Gelatinase–Associated lipocalin as an early and reliable biomarker of diabetic nephropathy in type 2 diabetes mellitus

Background: Early detection of diabetic nephropathy (DN) remains a major clinical challenge. Conventional indicators such as serum creatinine and urinary albumin excretion often identify renal impairment only after significant structural damage has occurred. Increasing evidence suggests that tubular injury may precede glomerular dysfunction in diabetic kidney disease. Neutrophil gelatinase-associated lipocalin (NGAL), a biomarker released from injured renal tubular epithelial cells, has therefore emerged as a potential early indicator of renal injury. Objective: This study aimed to evaluate the diagnostic performance of urinary NGAL as an early biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus and to compare its performance with conventional renal function markers. Methods: A cross-sectional study was conducted including 90 participants: 72 patients with type 2 diabetes mellitus and 18 healthy controls. Diabetic patients were categorized into four stages of nephropathy according to estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) based on KDIGO criteria. Urinary NGAL concentrations were measured using a sandwich enzyme-linked immunosorbent assay (ELISA). Statistical analysis included correlation analysis, receiver operating characteristic (ROC) curve assessment, and multivariate logistic regression. Results: Urinary NGAL levels increased progressively with the severity of diabetic nephropathy, rising from 49.1 ± 14.2 ng/mL in controls (within the normal reference range < 70 ng/mL) to 547.7 ± 31.7 ng/mL in patients with stage IV disease (p < 0.001). NGAL demonstrated a strong positive correlation with serum creatinine (r = 0.81) and urinary ACR (r = 0.76), and a significant negative correlation with eGFR (r = - 0.79). ROC curve analysis showed that NGAL exhibited excellent diagnostic performance (AUC = 1.00), outperforming ACR (AUC = 0.97) and serum creatinine (AUC = 0.83). An optimal cutoff value of 107.3 ng/mL provided high sensitivity and specificity for detecting diabetic nephropathy in this cohort. Conclusion: Urinary NGAL appears to be a sensitive biomarker of renal tubular injury and may allow earlier identification of diabetic nephropathy compared with conventional markers. Incorporation of NGAL measurement into clinical evaluation may improve early detection of diabetic kidney disease, although larger prospective studies are required to confirm these findings.