Urinary Uromodulin for Distinguishing Between Glomerulonephritis, Diabetic Kidney Disease, and Nephrosclerosis in a Biopsy-Proven Cohort

Background/Objectives: Distinguishing glomerulonephritis (GN) from diabetic kidney disease (DKD) and nephrosclerosis (NS) is clinically important. Urinary uromodulin (uUMOD), a biomarker of renal tubular integrity, may help discriminate among these chronic kidney disease (CKD) etiologies. We evaluated the diagnostic utility of uUMOD for differentiating GN from DKD and NS. Methods: This retrospective single-center study included 90 patients with biopsy-proven GN (n = 30), DKD (n = 25), or NS (n = 35). First-morning spot urine samples obtained before biopsy were analyzed for uUMOD concentration and normalized to urinary creatinine levels (uUMOD/Cr). Results: The uUMOD/Cr ratio was significantly higher in GN (21.2 mg/gCr [10.3-31.3]) than in DKD (5.5 [3.6-12.3], p < 0.001) or NS (10.7 [6.4-19.9], p = 0.021). In multivariate analyses adjusted for age, sex, estimated glomerular filtration rate, interstitial fibrosis, and urinary protein, the uUMOD/Cr ratio was independently associated with GN (p = 0.003) and this correlation remained statistically significant after additional adjustment for diabetes mellitus. Receiver operating characteristic curve analysis showed an area under the curve value of 0.833 for GN versus DKD, 0.714 for GN versus NS, and 0.764 for GN versus DKD and NS combined. A cutoff value of 16.5 mg/gCr yielded 72.8% sensitivity and 70.0% specificity for identifying GN. Conclusions: uUMOD secretion is preserved in GN compared to DKD or NS and shows moderate diagnostic utility for differentiating between these biopsy-proven CKD etiologies. uUMOD may serve as a simple, noninvasive biomarker when biopsy is difficult or clinical findings are inconclusive.