Serum Uromodulin, a Potential Biomarker of Tubulointerstitial Damage, Correlates Well with Measured GFR and ERPF in Patients with Obstructive Nephropathy.

Abstract

Background and Objectives: In chronic kidney obstruction, the severity of tubulointerstitial damage correlates best with the loss of kidney function and the risk for progression to end-stage kidney disease. The present study aimed to investigate the potential clinical significance of serum uromodulin (sUmod) as a marker of early kidney disfunction in patient with obstructive nephropathy (ON). Materials and Methods: Serum Umod level was measured by sensitive ELISA method in 57 adult patients with obstructive nephropathy and 25 healthy subjects in control group. Kidney function was precisely evaluated via measured glomerular filtration rate (mGFR) (renal clearance of 99 mTc-diethylenetriamine penta-acetic acid), effective renal plasma flow (ERPF) and Cystatin C level. Recruited patients were divided into subgroups based on the mGFR: group I-GFR ≤ 60 mL/min/1.73 m2 (N = 31), group II-GFR > 60 mL/min/1.73 m2 (N = 26). Results: A significantly lower level of serum uromodulin was measured in patients with ON (50.2 ± 26.3 ng/mL) compared to the control group (78.3 ± 24.5 ng/mL) (p < 0.001). The mean level of serum Umod was significantly different between group I (30.5 ng/mL ± 11.1) and group II (73.6 ng/mL ± 18.6) (p < 0.001), but not between group II (73.6 ng/mL ± 18.6) and control group (78.3 ± 24.5 ng/mL). There was a positive correlation between sUmod and mGFR (R = 0.757, p < 0.001) and ERPF (R = 0.572 p < 0.001), with lower sUmod levels in patients with impaired renal function. An inverse relationship was detected between sUmod and filtration markers-cystatin C (R = -0.625, p < 0.001), creatinine, urea and uric acid. ROC analysis of sUmod to differentiate between ON patients with GFR below 60 mL/min/1.73 m2 and above 60 mL/min/1.73 m2 resulted in AUC of 0.98 (p < 0.001, 95% CI 0.922 vs. 0.998) at a cut-off value of 46 ng/mL (specificity 96.8%, sensitivity 92.2%). Conclusions: The significant correlation of sUmod with kidney function parameters may imply potential clinical significance as a noninvasive biomarker of early kidney disfunction in obstructive nephropathy.