Febuxostat and renal outcomes: post-hoc analysis of a randomized trial

Kentaro Kohagura; Sunao Kojima; Kazuaki Uchiyama; Naoto Yokota; Eiichi Tokutake; Yutaka Wakasa; Shinya Hiramitsu; Masako Waki; Hideaki Jinnouchi; Hirokazu Kakuda; Takahiro Hayashi; Naoki Kawai; Masahiro Sugawara; Hisao Mori; Kenichi Tsujita; Kunihiko Matsui; Ichiro Hisatome; Yusuke Ohya; Kazuo Kimura; Yoshihiko Saito; Hisao Ogawa; Febuxostat for Cerebral and Cardiorenovascular Events Prevention Study (FREED) investigators

doi:10.1038/s41440-023-01198-x

Febuxostat and renal outcomes: post-hoc analysis of a randomized trial

Hypertens Res. 2023 Jun;46(6):1417-1422. doi: 10.1038/s41440-023-01198-x. Epub 2023 Feb 7.

Authors

Kentaro Kohagura¹, Sunao Kojima², Kazuaki Uchiyama³, Naoto Yokota⁴, Eiichi Tokutake⁵, Yutaka Wakasa⁶, Shinya Hiramitsu⁷, Masako Waki⁸, Hideaki Jinnouchi⁹, Hirokazu Kakuda¹⁰, Takahiro Hayashi¹¹, Naoki Kawai¹², Masahiro Sugawara¹³, Hisao Mori¹⁴, Kenichi Tsujita¹⁵, Kunihiko Matsui¹⁶, Ichiro Hisatome¹⁷, Yusuke Ohya¹⁸, Kazuo Kimura¹⁹, Yoshihiko Saito²⁰, Hisao Ogawa²¹; Febuxostat for Cerebral and Cardiorenovascular Events Prevention Study (FREED) investigators

Affiliations

¹ Dialysis Unit, University of the Ryukyus Hospital, Nishihara, Japan. [email protected].
² Department of Internal Medicine, Sakurajyuji Yatsushiro Rehabilitation Hospital, Yatsushiro, Japan.
³ Uchiyama Clinic, Joetsu, Japan.
⁴ Yokota Naika, Miyazaki, Japan.
⁵ Tokutake Iin, Kawaguchi, Japan.
⁶ Wakasa Medical Clinic, Kanazawa, Japan.
⁷ Hiramitsu Heart Clinic, Nagoya, Japan.
⁸ Shizuoka City Shizuoka Hospital, Shizuoka, Japan.
⁹ Jinnouchi Hospital Diabetes Care Center, Kumamoto, Japan.
¹⁰ Kakuda Iin, Kahoku, Japan.
¹¹ Hayashi Medical Clinic, Sakai, Japan.
¹² Kawai Naika Clinic, Gifu, Japan.
¹³ Sugawara Clinic, Tokyo, Japan.
¹⁴ Fuji Health Promotion Center, Fuji, Japan.
¹⁵ Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
¹⁶ Department of Community, Family, and General Medicine, Kumamoto University Hospital, Kumamoto, Japan.
¹⁷ Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science, Yonago, Japan.
¹⁸ Department of Cardiovascular Medicine, Nephrology and Neurology, University of the Ryukyus School of Medicine, Okinawa, Japan.
¹⁹ Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan.
²⁰ Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Japan.
²¹ Kumamoto University, Kumamoto, Japan.

PMID: 36750608
DOI: 10.1038/s41440-023-01198-x

Abstract

Effect of urate-lowering on renal outcomes in patients at high-risk for cardiovascular disease with hyperuricemia without gout is not known. We conducted a post hoc analysis of a randomized trial (Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy [FREED]). The FREED trial enrolled 1070 asymptomatic, hyperuricemic elderly patients with at least one risk factor for cardiovascular disease, divided into febuxostat (n = 537) and non-febuxostat (n = 533) groups. We compared the effect of these treatments on renal outcomes including 40% decline in estimated glomerular filtration rate, new onset of microalbuminuria and development or worsening macroalbuminuria. The relative risk of developing or worsening macroalbuminuria was 56% lower in the febuxostat group (hazard ratio, 0.44; 95% CI, 0.24-0.82; P = 0.0098). However, the risks for other outcomes were comparable. In patients with asymptomatic hyperuricemia without gout, febuxostat reduces the risk of development or worsening of macroalbuminuria.

Keywords: Albuminuria; Chronic kidney disease; Febuxostat; Hyperuricemia; Randomized clinical trial.

Publication types

Randomized Controlled Trial

MeSH terms

Aged
Cardiovascular Diseases* / drug therapy
Febuxostat / therapeutic use
Gout Suppressants / therapeutic use
Gout* / complications
Gout* / drug therapy
Humans
Hyperuricemia* / complications
Hyperuricemia* / drug therapy
Treatment Outcome
Uric Acid

Substances

Febuxostat
Gout Suppressants
Uric Acid