Febuxostat treatment for hyperuricemia may reduce macroalbuminuria risk, according to a post hoc analysis of the FREED trial.1

In FREED (Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy), investigators randomly assigned 1070 patients aged 65 years and older who had hyperuricemia (serum uric acid of 7-9 mg/dL) and 1 or more risk factors for cardiorenovascular disease to treatment with febuxostat (target dose 40 mg/day) or without febuxostat (up to 20% of the control group received allopurinol). At baseline, no patients had gout or an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2. The median baseline urinary albumin to creatinine ratio (UACR) was less than 20 mg/g creatinine. The vast majority of patients had hypertension.  

The original trial showed a 25% reduction in a composite cardiorenal outcome with febuxostat, a xanthine oxidase inhibitor, over 36 months.2 Serum uric acid level declined significantly more with febuxostat treatment: 4.50 vs 6.76 mg/dL, respectively.

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The post hoc analysis revealed that use of febuxostat for hyperuricemia was significantly associated with a 56% reduced risk of new or worsening macroalbuminuria greater than 300 mg/g creatinine, Kentaro Kohagura, MD, of the University of the Ryukyus Hospital in Nishihara, Japan, and colleagues reported in Hypertension Research. Results did not differ by baseline eGFR or UACR. The investigators found no differences in the risk of a 40% decline in eGFR or new onset microalbuminuria (UACR 30 to less than 300 mg/g).

The investigators observed no significant differences in annual changes in eGFR and UACR.

According to Dr Kohagura’s team, febuxostat’s effects on endothelial dysfunction may be responsible for the reduced risk of macroalbuminuria.

In an accompanying editorial, Kouichi Tamura, MD, of Yokohama City University Graduate School of Medicine in Japan, and colleagues suggested that a combination of drug and patient background may influence whether urate-lowering therapy is renoprotective.3

Disclosure: This trial was supported by Teijin Pharma Limited. Please see the original reference for a full list of disclosures.


  1. Kohagura K, Kojima S, Uchiyama K, et al. Febuxostat and renal outcomes: post-hoc analysis of a randomized trial. Hypertens Res. Published online February 7, 2023. doi:10.1038/s41440-023-01198-x
  2. Kojima S, Matsui K, Hiramitsu S, Hisatome I, Waki M, UchiyamaK, et al. Febuxostat for cerebral and CaRdiorenovascular Events PrEvEntion StuDy. Eur Heart J. 2019;40:1778–86. doi:10.1093/eurheartj/ehz119
  3. Tsukamoto SI, Wakui H, Tamura K. Effects of uric acid-lowering therapy on the kidney. Hypertens Res. Published online March 8, 2023. doi:10.1038/s41440-023-01252-8