Superior effect of allopurinol compared to febuxostat on the retardation of chronic kidney disease progression

BACKGROUND: Although hyperuricemia is associated with chronic kidney disease, whether and how it should be managed for renoprotection remains debatable. Thus, we investigated whether allopurinol and febuxostat, the most frequently used urate-lowering treatments, have differential renoprotective effects on chronic kidney disease. METHODS: Incident users of allopurinol and febuxostat were identified from two tertiary referral centers. One-to-one propensity score matching between the allopurinol and febuxostat groups was performed. Participants were followed up until the occurrence of clinical outcomes, urate-lowering agent discontinuation, mortality, or the end of the study period, whichever occurred first. The primary outcomes were a 30% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease. Differential trends of eGFR decline were estimated using a linear mixed-effects model. RESULTS: Each group included 654 participants. Baseline eGFRs were 40.1 [26.6–57.3] and 39.1 [27.9–58.3] mL/min/1.73 m(2) in the allopurinol and febuxostat group, respectively. Adjusted least square mean change in serum urate was −1.58 mg/dL [95% confidence interval (CI), −1.78 to −1.38] and -2.69 mg/dL (95% CI, −2.89 to −2.49) in the allopurinol and febuxostat groups, respectively. Despite lower serum urate levels, febuxostat was significantly more associated with a 30% decline in eGFR (hazard ratio 1.26; 95% CI 1.03–1.54) and end-stage renal disease (hazard ratio 1.91, 95% CI 1.42–2.58) than allopurinol. Annual eGFR decline in febuxostat users was estimated to be more rapid than in allopurinol users by 2.14 (standard error 0.71) mL/min/1.73 m(2) per year. CONCLUSIONS: Allopurinol demonstrated attenuation of chronic kidney disease progression and prevention of hypouricemia, compared to febuxostat. Because the treatment can be renoprotective, further studies on its effects on chronic kidney disease are required.