Evaluation of Serum Levels of Uromodulin, Neutrophil Gelatinase-Associated Lipocalin, and CD4+ T Cell Percentages as Diagnostic Biomarkers in Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN) remains the leading cause of end- Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease worldwide. Early detection is challenging as conventional markers only become abnormal after significant kidney damage has occurred. Uromodulin (UMOD) is a highly organ-specific marker of tubular integrity. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is released from tubular epithelial cells within hours of injury, providing an early signal of tubular stress. CD4+ T-cell activation may contribute to disease progression through pro-inflammatory cytokines and promotion of kidney tissue injury. The study aimed to evaluate serum UMOD, NGAL, and CD4+ T-cell percentages as potential biomarkers for DN. A case-control study was conducted between September 2025 and April 2026 at Al-Sadr Teaching Hospital and Al-Hakim General Hospital, Najaf, Iraq, enrolling 60 healthy controls, 30 T2DM patients, and 30 DN patients. Serum UMOD and NGAL were quantified by sandwich ELISA. CD4+ T-cell percentages were determined by flow cytometry. Diagnostic performance was assessed by ROC curve analysis. Serum UMOD and NGAL were significantly elevated in T2DM and DN compared to controls (P < 0.001). CD4+ T-cell percentages were significantly higher in T2DM and DN patients than in controls (P < 0.001). ROC analysis showed excellent-to-perfect discrimination (AUC = 0.802–1.000) for all biomarkers; serum NGAL achieved the highest AUC values (0.995 for T2DM; 1.000 for DN). Serum UMOD, NGAL, and CD4+ T-cell percentages were significantly increased in T2DM and DN patients and showed strong diagnostic performance. These markers may serve as useful noninvasive tools for the early detection and monitoring of DN.