Relationship between Serum Uric Acid and Mortality Risk in Hemodialysis Patients: A Multicenter Prospective Cohort Study

Abstract

<b><i>Background:</i></b> Several studies have reported that low serum uric acid (SUA) levels are related to increased risk of mortality in maintenance hemodialysis (MHD) patients. However, the possible detrimental effects of high SUA on the mortality risk have not been well examined. Moreover, the possible effect modifiers for the SUA-mortality association have not been fully investigated. To address the aforementioned gap, we aimed to explore the nonlinear relationship between SUA levels and all-cause and cardiovascular disease (CVD) mortality risk, and to examine any possible effect modifiers in MHD patients. <b><i>Methods:</i></b> We conducted a multicenter, prospective cohort study among 1,018 MHD patients from 8 hemodialysis centers. The primary outcome was all-cause mortality, and the secondary outcomes were CVD mortality and non-CVD mortality. <b><i>Results:</i></b> The mean value for SUA in the total population was 8.5 ± 1.9 mg/dL. The lowest and highest quintiles of SUA were <7.0 and >10.1 mg/dL, respectively. Over a median follow-up of 45.6 months, 343 deaths were recorded, of which 202 (58.9%) were due to CVD. When SUA was assessed as quintiles, a significantly higher risk of all-cause mortality was found in patients in quintile 1 (<7.0 mg/dL; hazard ratio [HR], 1.33; 95% confidence interval [CI]: 1.02–1.73) or quintile 5 (≥10.1 mg/dL; HR, 1.47; 95% CI: 1.09–2.00), compared to those in quintiles 2–4 (7–10.1 mg/dL). Moreover, the U-shaped SUA-mortality association was mainly found in those with lower C-reactive protein levels (<3 compared with ≥3 mg/L; <i>p</i> for interaction = 0.018). Similar trends were found for CVD mortality and non-CVD mortality. <b><i>Conclusion:</i></b> There was a U-shaped relationship between SUA levels and the risk of all-cause mortality, CVD mortality, and non-CVD mortality in MHD patients.

Are serum uric acid levels predictors of cardiovascular risk? An update

“…This U-shaped association was confirmed in both sexes; the inflection point for serum uric acid was 4 mg/dl (238 μmol/l) in women and 6 mg/dl (357 μmol/l) in men [27]. A similar U-shaped association of serum uric acid with all-cause and CVD mortality has recently been reported in other general population cohorts [28,29 ▪ ,30 ▪ ,31], the elderly [32,33], patients with type 2 diabetes mellitus [34] and patients with chronic kidney disease undergoing haemodialysis [35–37].…”

The Association Between the Serum Uric Acid to Creatinine Ratio and All-Cause Mortality in Elderly Hemodialysis Patients

“…A large cohort study in Japan showed that uric acid levels may have a U-shaped association with all-cause mortality among the general population, which means that both low and high uric acid levels may increase mortality [31]. Consistently, a multicenter prospective cohort study in Chinese hemodialysis patients also certi ed a U-shaped pattern between serum uric acid level and all-cause mortality, cardiovascular disease (CVD) mortality and non-CVD mortality [32].…”

The association between the serum uric acid to creatinine ratio and all-cause mortality in elderly hemodialysis patients

“…A large cohort study in Japan showed that uric acid levels may have a U-shaped association with all-cause mortality among the general population, which means that both low and high uric acid levels may increase mortality [ 36 ]. Consistently, a multicenter prospective cohort study in Chinese hemodialysis patients also certified a U-shaped pattern between serum uric acid level and all-cause mortality, cardiovascular disease (CVD) mortality and non-CVD mortality [ 37 ].…”