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Research Article: Diagnostic value of tubular and glomerular biomarkers across different stages of kidney injury in patients with type 2 diabetic nephropathy

Date Published: 2026-06-18

Abstract:
Diabetic nephropathy (DN) remains a major cause of chronic kidney disease in patients with type 2 diabetes mellitus (T2DM), yet conventional markers incompletely capture heterogeneous renal injury. This study aimed to evaluate the diagnostic performance and stage-wise behavior of clinically accessible urinary glomerular and tubular biomarkers for identifying DN. This multicenter retrospective observational study enrolled 320 hospitalized patients with T2DM, including 160 patients with DN and 160 age- and sex-matched controls without nephropathy. Kidney function was stratified by estimated glomerular filtration rate (eGFR) categories G1 to G5. Urinary glomerular and tubular biomarkers were compared between groups and across stages. Receiver operating characteristic analysis, multivariable logistic regression, DeLong testing, calibration assessment, bootstrap internal validation, subgroup analysis, and sensitivity analyses were performed. Both glomerular and tubular biomarkers were significantly elevated in DN, with separation from controls evident even in G1. Urine albumin-to-creatinine ratio (UACR) showed the highest single-marker discrimination for DN (area under the curve 0.93, 95% confidence interval 0.90 to 0.96), followed by urinary albumin (0.91, 0.88 to 0.94) and urinary ?2-microglobulin (0.88, 0.84 to 0.92). For stage discrimination, urinary ?2-microglobulin performed best (area under the curve 0.85, 95% confidence interval 0.79 to 0.91). A combined model incorporating UACR, urinary ?2-microglobulin, and urinary N-acetyl-?-D-glucosaminidase improved discrimination versus UACR alone (area under the curve 0.96 vs 0.93; DeLong Z = 2.74, P = 0.006), with good calibration and stable performance after bootstrap validation and sensitivity analyses. Clinically available urinary tubular and glomerular biomarkers distinguish DN from matched T2DM controls across Kidney Disease: Improving Global Outcomes (KDIGO) eGFR stages, including preserved eGFR. Integrating tubular injury markers with UACR significantly enhances diagnostic performance beyond UACR alone.

Introduction:
Diabetic nephropathy (DN) remains a major cause of chronic kidney disease in patients with type 2 diabetes mellitus (T2DM), yet conventional markers incompletely capture heterogeneous renal injury. This study aimed to evaluate the diagnostic performance and stage-wise behavior of clinically accessible urinary glomerular and tubular biomarkers for identifying DN.

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