Abstract
The prevalence of hyperuricemia and chronic kidney disease (CKD) has been steadily increasing. The role of hyperuricemia and efficacy of uric acid-lowering agents against CKD progression remain controversial. This study aimed to evaluate the effect of hyperuricemia and uric acid-lowering agents on the progression of CKD. A total 2042 patients with CKD were analyzed in the KoreaN cohort Study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD), a prospective cohort study. Patients were classified into quartiles on the basis of their serum uric acid level and the prevalence of advanced CKD was higher in patients with a high uric acid level. A composite renal outcome was defined as one or more of the following: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate during the follow-up period. A Cox proportional hazard ratio model was applied to analyze the relationship between composite renal outcome and uric acid levels. The risk of progression to renal failure increased by 28% (hazard ratio [HR], 1.277; 95% confidence interval [CI], 1.212–1.345) for each 1 mg/dl increase in the baseline uric acid level. In multivariate models, an association was found between the highest quartile of uric acid and increased risk of composite renal outcome (HR, 3.590; 95% CI, 2.546–5.063). A propensity score matching analysis was performed to survey the effect of uric acid lowering agent. Both allopurinol and febuxostat did not affect the renal outcome. In conclusion, hyperuricemia appears to be an independent risk factor for composite renal outcome, but allopurinol and febuxostat did not show reno-protective effect.
Highlights
Uric acid, a final oxidation metabolite of purine in humans, is presumed to have an antioxidant effect and is mainly excreted in urine[1]
Distinguishing the exact effect of serum uric acid levels on chronic kidney disease (CKD) progression is of great importance
This study aimed to determine the correlation between serum uric acid levels and CKD progression and to identify the role of uric acid-lowering agents through analysis of the data of the KNOW-CKD study
Summary
A final oxidation metabolite of purine in humans, is presumed to have an antioxidant effect and is mainly excreted in urine[1]. Weiner et al.[9] reported that elevated serum uric acid level is a modest, independent risk factor for incident kidney disease in the general population. Krishnan et al.[10] showed that male veterans with gout and serum uric acid levels >7 mg/dl had an increased incidence of kidney disease. Kim et al.[11] analyzed the effect of hyperuricemia in patients with end-stage renal disease and found an association between higher uric acid level and lower all-cause mortality and no significant relationship with cardiovascular mortality. A study of patients with stages 3 to 4 CKD, demonstrated that hyperuricemia appears to be an independent risk factor for all-cause and cardiovascular mortality, but not kidney failure. This study aimed to determine the correlation between serum uric acid levels and CKD progression and to identify the role of uric acid-lowering agents through analysis of the data of the KNOW-CKD study
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