Association of Serum Uromodulin With ESKD and Kinney Function Decline in the Elderly: The Cardiovascular Health Study

Rationale & Objective: Uromodulin is released by tubular epithelial cells into the serum and lower levels are associated with more severe interstitial fibrosis and tubular atrophy. Low serum uromodulin (sUMOD) levels are associated with mortality and cardiovascular disease. However, little is known about the association of sUMOD levels with long-term kidney outcomes in older adults, a population with a high prevalence of interstitial fibrosis and tubular atrophy. Study Design: Case-cohort study and case-control study. Setting & Participants: Random subcohort (n = 933) and additional cases of end-stage kidney disease (ESKD) and kidney function decline (>= 30% decline in estimated glomerular filtration rate [eGFR]) during follow-up of the Cardiovascular Health Study (CHS). Predictor: sUMOD level. Outcomes: ESKD (n = 14) from the random subcohort and all additional ESKD cases from outside the random subcohort (n = 39) during follow-up (10 years, case-cohort study); kidney function decline of >= 30% eGFR at 9 years of follow-up in individuals with repeated eGFR assessments from the random subcohort (n = 56) and additional cases (n = 123). 224 participants from the random subcohort served as controls (case-control study). Analytical Approach: Modified multivariable Cox regression for ESKD and multivariable logistic regression for kidney function decline. Both analyses adjusted for demographics, eGFR, urinary albumin-creatinine ratio, and other kidney disease progression risk factors. Results: Mean age of the random subcohort was 78 years, 40% were men, 15% were black. Mean sUMOD level was 127 +/- 64 ng/mL and eGFR was 63 +/- 19 mL/min/1.73 m(2). In multivariable analysis, each 1-SD higher sUMOD level was associated with 63% lower risk for ESKD (HR, 0.37; 95% CI, 0.14-0.95). In demographic-adjusted analyses of kidney function decline, each 1-SD higher sUMOD level was associated with 25% lower odds of kidney function decline (OR, 0.75; 95% CI, 0.60-0.95); after multivariable adjustment, the association was attenuated and no longer significant (OR, 0.88; 95% CI, 0.68-1.14). Limitations: Possibility of survival bias in the kidney function decline analysis. Conclusions: Higher sUMOD levels may identify elderly persons at reduced risk for ESKD.