Association of Serum Uromodulin with Death, Cardiovascular Events, and Kidney Failure in CKD

Background and objectivesUromodulin is exclusively produced by tubular epithelial cells and released into urine and serum. Higher serum uromodulin has been associated with lower risk for kidney failure in Chinese patients with CKD andwith lower risk for mortality in the elderly and in patients undergoing coronary angiography. We hypothesizedthat lower serumuromodulinis associatedwithmortality, cardiovascular events, andkidneyfailure in white patients with CKD. Design, setting, participants,& measurements We measured serum uromodulin in 5143 participants enrolled in the German CKD (GCKD) study. The associations of baseline serum uromodulin with all-cause mortality, major adverse cardiovascular events (MACE; a composite of cardiovascularmortality, nonfatalmyocardial infarction or stroke, or incident peripheral vascular disease), and kidney failure (dialysis or transplantation) were evaluated using multivariable Cox proportional hazard regression analyses in a cohort study design, adjusting for demographics, eGFR, albuminuria, cardiovascular risk factors, and medication. Results The mean age of participants was 60 +/- 12 years, 60% were male. Mean serum uromodulin concentration was 98 +/- 60 ng/ml, eGFR was 49 +/- 18 ml/min per 1.73m(2), and 78% had eGFR <60 ml/min per 1.73m(2). Participants in lower serum uromodulin quartiles had lower eGFR and higher albumin uria, prevalence of diabetes, hypertension, coronary artery disease, and more frequent history of stroke at baseline. During a follow-up of 4 years, 335 participants died, 417 developedMACE, and 229 developed kidney failure. Inmultivariable analysis, the highest serumuromodulinquartilewas associatedwithlowerhazardformortality(hazardratio [HR], 0.57; 95% CI, 0.38 to 0.87), MACE (HR, 0.63; 95% CI, 0.45 to 0.90), and kidney failure (HR, 0.24; 95% CI, 0.10 to 0.55) comparedwith the lowest quartile. Conclusions Higher serumuromodulin is independently associated with lower risk for mortality, cardiovascular events, and kidney failure in white patients with CKD.