• Dominik Steubl, Petra Buzkova, Pranav S Garimella, Joachim H Ix, Prasad Devarajan, Michael R Bennett, Paolo H M Chaves, Michael G Shlipak, Nisha Bansal, and Mark J Sarnak.
• Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA; Division of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
• Am. J. Kidney Dis. 2019 Oct 1; 74 (4): 501-509.

Rationale & ObjectiveUromodulin 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 DesignCase-cohort study and case-control study.Setting & ParticipantsRandom 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).PredictorsUMOD level.OutcomesESKD (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 ApproachModified 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.ResultsMean age of the random subcohort was 78 years, 40% were men, 15% were black. Mean sUMOD level was 127±64ng/mL and eGFR was 63±19mL/min/1.73m2. 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).LimitationsPossibility of survival bias in the kidney function decline analysis.ConclusionsHigher sUMOD levels may identify elderly persons at reduced risk for ESKD.Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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