title: Urinary uromodulin, kidney function, and cardiovascular disease in elderly adults.
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.
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: Pranav S
authors.initials: PS
authors.lastname: Garimella
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington, USA.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Biggs
authors.affiliation: Kidney Research Institute, University of Washington, Seattle, Washington, USA.
authors.forename: Ronit
authors.initials: R
authors.lastname: Katz
authors.affiliation: Division of Nephrology, Universty of California, San Diego, San Diego, California, USA.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: Department of Nephrology and Hypertension, Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bennett
authors.affiliation: Department of Nephrology and Hypertension, Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.affiliation: Kidney Research Institute and Harborview Medical Center, University of Washington, Seattle, Washington, USA.
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Kestenbaum
authors.affiliation: New York Academy of Medicine, New York, New York, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Majken K
authors.initials: MK
authors.lastname: Jensen
authors.affiliation: Division of General Internal Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.affiliation: Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA.
authors.forename: Paulo H M
authors.initials: PH
authors.lastname: Chaves
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Sarnak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000652:urine; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D016016:Proportional Hazards Models; D058949:Uromodulin / Q000652:urine*
chemical_list: D015415:Biomarkers; D058949:Uromodulin; D003404:Creatinine