Uric Acid and Long-term Outcomes in CKD

Abstract

Background Hyperuricemia is prevalent in chronic kidney disease (CKD); however data are limited on 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 1989–1993, to examine the effects of strict blood pressure control and dietary protein restriction on progression of stage 3–4 CKD. This analysis included 838 patients. Predictor Uric acid Outcomes & Measurements The study evaluated the association of baseline uric acid levels with all-cause mortality, cardiovascular (CVD) mortality, and kidney failure. Results Mean (SD) age was 52 (12) years, glomerular filtration rate was 33 (12) ml/min/1.73m2, and uric acid was 7.63 (1.66) mg/dl. During a median follow-up of 10 years, 208 (25%) participants died of any cause, 127 (15%) from CVD, and 553 (66%) reached kidney failure. In multivariate models, the highest tertile of uric acid was associated with increased risk of all-cause (HR, 1.57 [95% CI, 1.07–2.32]) mortality, a trend towards CVD mortality (HR, 1.47 [95% CI, 0.90–2.39]) and no association with kidney failure (HR, 1.20 [95% CI, 0.95–1.51), compared to the lowest tertile. In continuous analyses, a 1-mg/dl higher uric acid was associated with 17% increased risk of all-cause (HR, 1.17 [95% CI, 1.05–1.30]), and 16% increased risk of CVD mortality (HR, 1.16 [95% CI, 1.01–1.33]), but was not associated with kidney failure (HR, 1.02 [95% CI, 0.97–1.07]). Limitations Primary analyses were based on single measurement of uric acid. The results are primarily generalizable to relatively young white patients with predominantly non-diabetic CKD. Conclusions In stage 3–4 CKD, hyperuricemia appears to be an independent risk factor for all-cause and CVD mortality but not kidney failure.