Association of serum uromodulin with mortality and cardiovascular disease in the elderly—the Cardiovascular Health Study
Year: 2019
Type: article
Abstract: BACKGROUND: Uromodulin (UMOD) is released by renal tubular cells into the serum (sUMOD) and urine. Lower urine UMOD has been linked to mortality and cardiovascular disease but much less is known about sUMOD. We evaluated the association of sUMOD with these outcomes in community-dwelling older adults. METHODS: We measured sUMOD in a random subcohort of 933 participants enrolled in the Cardiovascular Health Study. The associations of sUMOD with all-cause mortality, incident heart failure (HF) and incident cardiovascular disease (CVD; myocardial infarction, stroke and mortality due to coronary disease or stroke) were evaluated using multivariable Cox regression, adjusting for study participants' demographics, estimated glomerular filtration rate (eGFR), albuminuria and CVD risk factors. Generalized additive models with splines were used to address the functional form of sUMOD with outcomes. Due to nonlinear associations of sUMOD with all outcomes, 2.5% of the values on either end of the sUMOD distribution were excluded from the analyses, limiting the range of sUMOD to 34.3-267.1 ng/mL. RESULTS: The mean age was 78 ± 5 years, 40% were male, sUMOD level was 127 ± 64 ng/mL, eGFR was 63 mL/min/1.73 m2 and 42% had CKD defined as eGFR <60 mL/min/1.73 m2. Patients in the lower sUMOD quartiles had lower eGFR and higher albuminuria (P < 0.01, respectively). During a median follow-up of 9.9 years, 805 patients died, 283 developed HF and 274 developed CVD. In multivariable analysis, higher sUMOD was significantly associated with a lower hazard for mortality {hazard ratio [HR] 0.89 [95% confidence interval (CI) 0.80-0.99] per 1 standard deviation (SD) higher sUMOD}, CVD [HR 0.80 (95% CI 0.67-0.96)] and the composite endpoint [HR 0.88 (95% CI 0.78-0.99)]; the association with HF was not statistically significant [HR 0.84 (95% CI 0.70-1.01)]. CONCLUSION: Higher sUMOD is independently associated with a lower risk for mortality and CVD in older adults.
DOI: 10.1093/ndt/gfz008
Institutions: Tufts University, Tufts Medical Center, TUM Klinikum, Technical University of Munich, University of Washington, University of California San Diego, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Florida International University, University of California, San Francisco
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1023702118, G1118486281, G125972088, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G270907595, G277826483, G2800149121, Kidney Tubular Damage and Dysfunction Identify a Novel Axis of Chronic Kidney Disease, G2962705247, G3220743633, G3294437106, G34347772, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G423252844, Epidemiology, Clinical Trials and Outcomes Research In Nephrology, Critical Translational Studies in Pediatric Nephrology, G5339631484, G5479317095, G5540580309, G5720911069, G5841494052, CHS Events Follow-up Study, G6005877605, G6645300850, CHS-Transition Phase, Role of Mitochondrial Health in Acute and Chronic Kidney Disease in Older Adults, G7133383594, CHS RETINAL READING CENTER, Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), G905887895
OpenAlex ID: W2990525323