Uric Acid and Long-term Outcomes in CKD

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 m(2), 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. Am J Kidney Dis 53:796-803. (C) 2009 by the National Kidney Foundation, Inc. All rights reserved.