Serum Uric Acid Independently Predicts Cardiovascular Events in Advanced Nephropathy

Background: Chronic kidney disease (CKD) is associated with increased risk for cardiovascular (CV) disease and is also associated with elevated uric acid, which is emerging as a nontraditional CV risk factor. We therefore evaluated uric acid as a risk factor for CV disease in subjects presenting to nephrologists with CKD who were not on medications known to alter endothelial function. Methods: 303 subjects with stage 3–5 CKD were followed for a mean of 39 months (range 6–46) and assessed for fatal and nonfatal CV events. Hyperuricemia was defined as uric acid >6.0 mg/dl for women and >7.0 mg/dl for men. In addition to other CV risk factors, endothelial function (flow-mediated dilatation), inflammatory markers (hsCRP), and insulin resistance (HOMA index and fasting insulin levels) were included in the analysis. We evaluated the association between uric acid and flow-mediated dilatation with linear regression. The impact of uric acid on composite CV events was assessed with Cox regression analysis. Results: Of a total of 303 patients, 89 had normouricemia and 214 had hyperuricemia. Both fatal (32 of 214 vs. 1 of 89 subjects) and combined fatal and nonfatal (100 of 214 vs. 13 of 89 subjects) CV events were more common in subjects with hyperuricemia compared with normal uric acid levels, and this was independent of estimated glomerular filtration rate, traditional CV risk factors including diabetes, hypertension and BMI, and nontraditional risk factors (hsCRP and endothelial function). The 46-month survival rate was 98.7% in the group with low uric acid compared to 85.8% in patients with high uric acid (p = 0.002). Conclusions: Hyperuricemia is an independent risk factor for CV events in subjects presenting with CKD who are not on medications known to alter endothelial function.