Uric Acid and Long-term Outcomes in CKD

Magdalena Madero, Mark J. Sarnak, Xuelei Wang, Tom Greene, Gerald J. Beck, John W. Kusek, Allan J Collins, Andrew S. Levey, Vandana Menon

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339 Scopus citations

Abstract

Background: Hyperuricemia is prevalent in patients with chronic kidney disease (CKD); however, data are limited about the relationship of uric acid levels with long-term outcomes in this patient population. Study Design: Cohort study. Setting & Participants: The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial (N = 840) conducted from 1989 to 1993 to examine the effects of strict blood pressure control and dietary protein restriction on progression of stages 3 to 4 CKD. This analysis included 838 patients. Predictor: Uric acid level. Outcomes & Measurements: The study evaluated the association of baseline uric acid levels with all-cause mortality, cardiovascular disease (CVD) mortality, and kidney failure. Results: Mean age was 52 ± 12 (SD) years, glomerular filtration rate was 33 ± 12 mL/min/1.73 m2, and uric acid level was 7.63 ± 1.66 mg/dL. During a median follow-up of 10 years, 208 (25%) participants died of any cause, 127 (15%) died of CVD, and 553 (66%) reached kidney failure. In multivariate models, the highest tertile of uric acid was associated with increased risk of all-cause mortality (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.07 to 2.32), a trend toward CVD mortality (HR, 1.47; 95% CI, 0.90 to 2.39), and no association with kidney failure (HR, 1.20; 95% CI, 0.95 to 1.51) compared with the lowest tertile. In continuous analyses, a 1-mg/dL greater uric acid level was associated with 17% increased risk of all-cause mortality (HR, 1.17; 95% CI, 1.05 to 1.30) and 16% increased risk of CVD mortality (HR, 1.16; 95% CI, 1.01 to 1.33), but was not associated with kidney failure (HR, 1.02; 95% CI, 0.97 to 1.07). Limitations: Primary analyses were based on a single measurement of uric acid. Results are generalizable primarily to relatively young white patients with predominantly nondiabetic CKD. Conclusions: In patients with stages 3 to 4 CKD, hyperuricemia appears to be an independent risk factor for all-cause and CVD mortality, but not kidney failure.

Original languageEnglish (US)
Pages (from-to)796-803
Number of pages8
JournalAmerican Journal of Kidney Diseases
Volume53
Issue number5
DOIs
StatePublished - May 2009

Bibliographical note

Funding Information:
Support: This study was supported by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) Grants K23 DK067303, K23 DK02904, K24 DK078204, and UO1 DK35073, and TAP Pharmaceutical Products Inc.

Keywords

  • Kidney disease
  • cardiovascular
  • kidney failure
  • mortality
  • outcomes
  • uric acid

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