Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia

A Randomized Trial

FEATHER Study Investigators

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)798-810
Number of pages13
JournalAmerican Journal of Kidney Diseases
Volume72
Issue number6
DOIs
Publication statusPublished - 01-12-2018

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Hyperuricemia
Chronic Renal Insufficiency
Placebos
Uric Acid
Glomerular Filtration Rate
Therapeutics
Creatinine
Serum
Gouty Arthritis
Information Services
Febuxostat
Proteinuria
Registries
Epidemiologic Studies
Dialysis
Japan
Clinical Trials
Kidney
Incidence

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

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title = "Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia: A Randomized Trial",
abstract = "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.",
author = "{FEATHER Study Investigators} and Kenjiro Kimura and Tatsuo Hosoya and Shunya Uchida and Masaaki Inaba and Hirofumi Makino and Shoichi Maruyama and Sadayoshi Ito and Tetsuya Yamamoto and Yasuhiko Tomino and Iwao Ohno and Yugo Shibagaki and Satoshi Iimuro and Naohiko Imai and Masanari Kuwabara and Hiroshi Hayakawa and Hiroshi Ohtsu and Yasuo Ohashi and Kenjiro Kimura and Tatsuo Hosoya and Sadayoshi Ito and Masaaki Inaba and Yasuhiko Tomino and Shunya Uchida and Hirofumi Makino and Seiichi Matsuo and Hisashi Yamanaka and Tetsuya Yamamoto and Iwao Ohno and Yugo Shibagaki and Satoshi Iimuro and Naohiko Imai and Masanari Kuwabara and Hiroshi Hayakawa and Tadao Akizawa and Tamio Teramoto and Hiroshi Kasanuki and Kenichi Yoshimura and Kenjiro Kimura and Tatsuo Hosoya and Yugo Shibagaki and Iwao Ohno and Hiroshi Sato and Shunya Uchida and Satoshi Horikoshi and Syoichi Maruyama and Masahiko Inaba and Yuji Moriwaki and Haruhito Uchida and Nagayuki Kaneshiro and Yukio Yuzawa",
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Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia : A Randomized Trial. / FEATHER Study Investigators.

In: American Journal of Kidney Diseases, Vol. 72, No. 6, 01.12.2018, p. 798-810.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia

T2 - A Randomized Trial

AU - FEATHER Study Investigators

AU - Kimura, Kenjiro

AU - Hosoya, Tatsuo

AU - Uchida, Shunya

AU - Inaba, Masaaki

AU - Makino, Hirofumi

AU - Maruyama, Shoichi

AU - Ito, Sadayoshi

AU - Yamamoto, Tetsuya

AU - Tomino, Yasuhiko

AU - Ohno, Iwao

AU - Shibagaki, Yugo

AU - Iimuro, Satoshi

AU - Imai, Naohiko

AU - Kuwabara, Masanari

AU - Hayakawa, Hiroshi

AU - Ohtsu, Hiroshi

AU - Ohashi, Yasuo

AU - Kimura, Kenjiro

AU - Hosoya, Tatsuo

AU - Ito, Sadayoshi

AU - Inaba, Masaaki

AU - Tomino, Yasuhiko

AU - Uchida, Shunya

AU - Makino, Hirofumi

AU - Matsuo, Seiichi

AU - Yamanaka, Hisashi

AU - Yamamoto, Tetsuya

AU - Ohno, Iwao

AU - Shibagaki, Yugo

AU - Iimuro, Satoshi

AU - Imai, Naohiko

AU - Kuwabara, Masanari

AU - Hayakawa, Hiroshi

AU - Akizawa, Tadao

AU - Teramoto, Tamio

AU - Kasanuki, Hiroshi

AU - Yoshimura, Kenichi

AU - Kimura, Kenjiro

AU - Hosoya, Tatsuo

AU - Shibagaki, Yugo

AU - Ohno, Iwao

AU - Sato, Hiroshi

AU - Uchida, Shunya

AU - Horikoshi, Satoshi

AU - Maruyama, Syoichi

AU - Inaba, Masahiko

AU - Moriwaki, Yuji

AU - Uchida, Haruhito

AU - Kaneshiro, Nagayuki

AU - Yuzawa, Yukio

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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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DO - 10.1053/j.ajkd.2018.06.028

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EP - 810

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

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