Urinary uromodulin, kidney function, and cardiovascular disease in elderly adults

Pranav S. Garimella, Mary L. Biggs, Ronit Katz, Joachim H. Ix, Michael R. Bennett, Prasad Devarajan, Bryan R. Kestenbaum, David S. Siscovick, Majken K. Jensen, Michael G. Shlipak, Paulo H.M. Chaves, Mark J. Sarnak

Research output: Contribution to journalArticle

Abstract

Urinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end-stage renal disease (ESRD), and in a random subcohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure, and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8 μg/ml. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each 1-s.d. higher uUMOD was associated with a 23% lower odds of eGFR decline (odds ratio 0.77 (95% CI 0.62-0.96)) and a 10% lower risk of mortality (hazard ratio 0.90 (95% CI 0.83-0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio, and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease, or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function.

Original languageEnglish (US)
Pages (from-to)1126-1134
Number of pages9
JournalKidney international
Volume88
Issue number5
DOIs
StatePublished - Nov 1 2015

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Keywords

  • Cardiovascular disease
  • Chronic kidney disease
  • Mortality
  • Tamm'Horsfall protein
  • Urinary biomarkers
  • Uromodulin

ASJC Scopus subject areas

  • Nephrology

Cite this

Garimella, P. S., Biggs, M. L., Katz, R., Ix, J. H., Bennett, M. R., Devarajan, P., Kestenbaum, B. R., Siscovick, D. S., Jensen, M. K., Shlipak, M. G., Chaves, P. H. M., & Sarnak, M. J. (2015). Urinary uromodulin, kidney function, and cardiovascular disease in elderly adults. Kidney international, 88(5), 1126-1134. https://doi.org/10.1038/ki.2015.192