The value of uromodulin as a new serum marker to predict decline in renal function.

Abstract

Uromodulin is the most abundant protein in urine. Low uromodulin has been found associated with diabetes as well as with chronic kidney disease (CKD). Whether it also predicts a future decline in kidney function is not known. We evaluated the association between serum uromodulin and kidney function in 529 patients and performed a genome-wide association study. Clinical parameters including renal function were determined at baseline and reassessed at a 4-year follow-up visit. Patients' serum uromodulin levels were highest associated with a polymorphism in the UMOD coding region and were significantly correlated with estimated glomerular filtration rate (eGFR) (r = 0.242, P < 0.001) and, in an inverse way, with the albumin-creatinine ratio (r = -0.120, P = 0.012). Serum uromodulin concentrations were significantly lower in patients with CKD (eGFR < 60 ml/min per 1.73 m) than in patients with normal kidney function (71.9 ± 29.0 vs. 169.1 ± 76.1 ng/ml, P < 0.001) and the same applied to patients with albuminuria (148.7 ± 72.2 vs. 167.9 ± 77.6 ng/ml, P = 0.008) or hypertension (160.9 ± 74.0 vs. 181.8 ± 87.8 ng/ml, P = 0.037). Prospectively, patients who developed CKD during the follow-up had significantly less uromodulin in serum than those who did not (126.8 ± 42.3 vs. 180.2 ± 79.1 ng/ml, P = 0.003). Serum uromodulin concentration was inversely associated with the development of CKD, even after adjustment for patients age, sex, genotype of the identified polymorphism, hypertension and diabetes status, and eGFR (odds ratio = 0.263, P = 0.019), and it significantly increased the performance of a prediction model for CKD (C-statistics 0.844 vs. 0.804, P = 0.049). The current study is the first evaluating the value of uromodulin in serum as a novel predictive biomarker for renal function and for the incidence of CKD.