Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia: A Randomized Trial

• DOI: 10.1053/j.ajkd.2018.06.028
• Publication Date: 2018-08-31T22:46:52Z
• Authors: 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; Kenjiro Kimura; Tatsuo Hosoya; Sadayoshi Ito; Masaaki Inaba; Yasuhiko Tomino; Shunya Uchida; Hirofumi Makino; Seiichi Matsuo; Hisashi Yamanaka; Tetsuya Yamamoto; Iwao Ohno; Yugo Shibagaki; Satoshi Iimuro; Naohiko Imai; Masanari Kuwabara; Hiroshi Hayakawa; Tadao Akizawa; Tamio Teramoto; Hiroshi Kasanuki; Kenichi Yoshimura; Kenjiro Kimura; Tatsuo Hosoya; Yugo Shibagaki; Iwao Ohno; Hiroshi Sato; Shunya Uchida; Satoshi Horikoshi; Syoichi Maruyama; Masahiko Inaba; Yuji Moriwaki; Haruhito Uchida; Nagayuki Kaneshiro; Naohiko Imai; Hidekazu Moriya; Yasuhiro Komatsu; Shinya Kaname; Kazunari Hanaoka; Makoto Ogura; Masato Ikeda; Kenji Kasai; Akira Sugiura; Kazushi Takahashi; Kenichiro Kojima; Kosaku Nitta; Hirofumi Tamai; Hiroshi Nagaya; Senji Okuno; Ryusuke Kakiya; Hiroya Takeoka; Kyouji Hirata; Kenichiro Asano; Yasuo Fukaya; Yasushi Iwaida; Yasuo Tsuneda; Shigeaki Nishimura; Takeyuki Hiramatsu; Yoshitaka Isaka; Takafumi Ito; Yukio Yuzawa; Kunihiro Yamagata; Tadashi Sofue; Yoshimi Jinguji; Keita Hirano; Kazuhiro Matsuyama; Teruhiko Mizumoto; Yuko Shibuya; Masahiro Sugawara; Moritoshi Kadomura; Yasuaki Teshima; Hiroshi Ohtani; Hiroki Kamata; Susumu Okawara; Masaki Fukushima; Katsumi Takemura; Eriko Kinugasa; Masami Kogure; Yoichi Ehara
• Keywords: Adult; Male; Age Factors; Hyperuricemia; Middle Aged; Risk Assessment; Severity of Illness Index; Gout Suppressants; 3. Good health; 03 medical and health sciences; Febuxostat; 0302 clinical medicine; Double-Blind Method; Japan; Reference Values; Asymptomatic Diseases; Disease Progression; Humans; Female; Renal Insufficiency, Chronic; Aged; Follow-Up Studies; Glomerular Filtration Rate

Epidemiologic and clinical studies have suggested that urate-lowering therapy may slow the progression of chronic kidney disease (CKD). However, definitive evidence is lacking.Randomized, double-blind, placebo-controlled trial.467 patients with stage 3 CKD and asymptomatic hyperuricemia at 55 medical institutions in Japan.Participants were randomly assigned in a 1:1 ratio to receive febuxostat or placebo for 108 weeks.The 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.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±5.26mL/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.GFR was estimated rather than measured, and patients with stages 4 and 5 CKD were excluded.Compared to placebo, febuxostat did not mitigate the decline in kidney function among patients with stage 3 CKD and asymptomatic hyperuricemia.Funded by Teijin Pharma Limited.Registered at the UMIN (University Hospital Medical Information Network) Clinical Trials Registry with study number UMIN000008343.