• Kenjiro Kimura, Tatsuo Hosoya, Shunya Uchida, Masaaki Inaba, Hirofumi Makino, Shoichi Maruyama, Sadayoshi Ito, Tetsuya Yamamoto, Yasuhiko Tomino, Iwao Ohno, Yugo Shibagaki, Satoshi Iimuro, Naohiko Imai, Masanari Kuwabara, Hiroshi Hayakawa, Hiroshi Ohtsu, Yasuo Ohashi, and FEATHER Study Investigators.
• Tokyo Takanawa Hospital, Tokyo, Japan. Electronic address: kimura-kenjiro@takanawa.jcho.go.jp.
• Am. J. Kidney Dis. 2018 Dec 1; 72 (6): 798-810.

Rationale & ObjectiveEpidemiologic and clinical studies have suggested that urate-lowering therapy may slow the progression of chronic kidney disease (CKD). However, definitive evidence is lacking.Study DesignRandomized, double-blind, placebo-controlled trial.Setting & Participants467 patients with stage 3 CKD and asymptomatic hyperuricemia at 55 medical institutions in Japan.InterventionParticipants were randomly assigned in a 1:1 ratio to receive febuxostat or placebo for 108 weeks.OutcomesThe primary end point was the slope (in mL/min/1.73m2 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.ResultsOf 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±5.26mL/min/1.73m2 per year) and placebo (-0.47±4.48mL/min/1.73m2 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.LimitationsGFR was estimated rather than measured, and patients with stages 4 and 5 CKD were excluded.ConclusionsCompared to placebo, febuxostat did not mitigate the decline in kidney function among patients with stage 3 CKD and asymptomatic hyperuricemia.FundingFunded by Teijin Pharma Limited.Trial RegistrationRegistered at the UMIN (University Hospital Medical Information Network) Clinical Trials Registry with study number UMIN000008343.Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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