Rationale & Objective: Epidemiologic and clinical studies have suggested that urate-lowering therapy may slow the progression of chronic kidney disease (CKD). However, definitive evidence is lacking. Study Design: Randomized, double-blind, placebo-controlled trial. Setting & Participants: 467 patients with stage 3 CKD and asymptomatic hyperuricemia at 55 medical institutions in Japan. Intervention: Participants were randomly assigned in a 1:1 ratio to receive febuxostat or placebo for 108 weeks. Outcomes: The primary end point was the slope (in mL/min/1.73 m2 per year) of estimated glomerular filtration rate (eGFR). Secondary end points included changes in eGFRs and serum uric acid levels at 24, 48, 72, and 108 weeks of follow-up and the event of doubling of serum creatinine level or initiation of dialysis therapy. Results: Of 443 patients who were randomly assigned, 219 and 222 assigned to febuxostat and placebo, respectively, were included in the analysis. There was no significant difference in mean eGFR slope between the febuxostat (0.23 ± 5.26 mL/min/1.73 m2 per year) and placebo (−0.47 ± 4.48 mL/min/1.73 m2 per year) groups (difference, 0.70; 95% CI, −0.21 to 1.62; P = 0.1). Subgroup analysis demonstrated a significant benefit from febuxostat in patients without proteinuria (P = 0.005) and for whom serum creatinine concentration was lower than the median (P = 0.009). The incidence of gouty arthritis was significantly lower (P = 0.007) in the febuxostat group (0.91%) than in the placebo group (5.86%). Adverse events specific to febuxostat were not observed. Limitations: GFR was estimated rather than measured, and patients with stages 4 and 5 CKD were excluded. Conclusions: Compared to placebo, febuxostat did not mitigate the decline in kidney function among patients with stage 3 CKD and asymptomatic hyperuricemia. Funding: Funded by Teijin Pharma Limited. Trial Registration: Registered at the UMIN (University Hospital Medical Information Network) Clinical Trials Registry with study number UMIN000008343.
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