Serum uric acid levels and health outcomes in CKD: a prospective cohort study

Background Hyperuricemia is prevalent in individuals with chronic kidney disease (CKD). Elevated serum uric acid (SUA) concentrations have been considered an independent risk factor for the onset of CKD. However, the relationship between SUA concentrations and long-term health outcomes among patients with CKD remains unclear.Methods We performed a prospective cohort study with nationally representative sample to investigate the relationship between SUA concentrations and mortality risk including all-cause, cardiovascular disease (CVD) and cancer mortality, among patients with CKD. The weighted restricted cubic spline analyses combined with the multivariate-adjusted Cox proportional hazard models were used to test the nonlinearity of relationship.Results The 6642 patients participating in National Health and Nutrition Examination Survey 1999-2018 were enrolled. During 656 885 person-months of follow-up time, 2619 all-cause deaths were recorded, including 1030 CVD deaths and 458 cancer deaths. Our study presented J-shaped non-linear relationships between SUA concentrations and all-cause and CVD mortality with inflection points at 311.65 mu mol/L and 392.34 mu mol/L, respectively. When SUA concentration was higher than those inflection points, every increase of 50 mu mol/L SUA was associated with 11.7% and 17.0% greater multivariable-adjusted hazard ratio of all-cause and CVD mortality, respectively. In addition, a negative linear correlation with cancer mortality was detected.Conclusion These findings suggested that maintaining appropriate SUA concentrations may improve long-term health outcomes among CKD patients. The corresponding inflection points of J-shaped non-linear relationships were 311.65 and 392.34 mu mol/L for all-cause and CVD mortality. Further clinical trials are required to investigate uric acid-lowering targets. Graphical Abstract

Automated summary

This study investigated the relationship between serum uric acid concentrations and mortality risk among patients with chronic kidney disease (CKD). The results demonstrated J-shaped non-linear relationships between uric acid concentrations and all-cause and cardiovascular disease mortality, with inflection points at 311.65 mu mol/L and 392.34 mu mol/L, respectively. Furthermore, a negative linear correlation with cancer mortality was observed. The study suggests that maintaining appropriate uric acid concentrations may improve long-term health outcomes among CKD patients.