Nakayama Shingo, Satoh Michihiro, Toyama Maya, Hashimoto Hideaki, Murakami Takahisa, Hirose Takuo, Obara Taku, Mori Takefumi, Metoki Hirohito
Division of Nephrology and Endocrinology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Division of Public Health, Hygiene and Epidemiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Clin Exp Nephrol. 2025 Jan 29. doi: 10.1007/s10157-025-02630-x.
Febuxostat and topiroxostat are non-purine selective xanthine oxidoreductase inhibitors commonly used for hyperuricaemia treatment in Japan. However, comparative data on the effects of febuxostat and topiroxostat on renal function and proteinuria are limited. This study compared proteinuria incidence and changes in the estimated glomerular filtration rate (eGFR) among prevalent febuxostat and topiroxostat users.
We conducted a retrospective cohort study using databases provided by DeSC Healthcare, Inc. (Tokyo, Japan). We identified 17,446 individuals (11.8% women; mean age 67.4 years) with eGFR ≥ 30 mL/min/1.73 m and no history of cardiovascular disease or proteinuria at baseline. Separate analyses were performed for individuals with eGFR < 60 mL/min/1.73 m and those with eGFR ≥ 60 mL/min/1.73 m. The adjusted hazard ratio (HR) for proteinuria incidence in topiroxostat users compared with febuxostat users was assessed using the Cox model. Changes in eGFR were compared between the two groups using multiple regression analysis.
During the mean follow-up period of 1.79 years, 1,433 participants developed proteinuria. In non-diabetic individuals with eGFR ≥ 60 mL/min/1.73 m, the adjusted HR for proteinuria incidence in topiroxostat users compared with febuxostat users was 0.60 (95% confidence interval, 0.40-0.91; p = 0.016). No significant differences were observed in eGFR changes between the two groups with eGFR < 60 and ≥ 60 mL/min/1.73 m.
Topiroxostat prevalent users had a lower risk of proteinuria than febuxostat prevalent users in non-diabetic individuals with eGFR ≥ 60 mL/min/1.73 m. Our findings suggest that topiroxostat might be more effective than febuxostat in preventing proteinuria in non-diabetic individuals with eGFR ≥ 60 mL/min/1.73 m.
非布司他和托匹司他是非嘌呤选择性黄嘌呤氧化还原酶抑制剂，在日本常用于治疗高尿酸血症。然而，关于非布司他和托匹司他对肾功能和蛋白尿影响的比较数据有限。本研究比较了非布司他和托匹司他现用者中蛋白尿的发生率以及估计肾小球滤过率（eGFR）的变化。
我们使用DeSC Healthcare公司（日本东京）提供的数据库进行了一项回顾性队列研究。我们确定了17446名个体（女性占11.8%；平均年龄67.4岁），其eGFR≥30 mL/min/1.73 m²，且基线时无心血管疾病或蛋白尿病史。对eGFR＜60 mL/min/1.73 m²的个体和eGFR≥60 mL/min/1.73 m²的个体分别进行分析。使用Cox模型评估托匹司他使用者与非布司他使用者相比蛋白尿发生率的调整后风险比（HR）。使用多元回归分析比较两组之间eGFR的变化。
在平均1.79年的随访期内，1433名参与者出现了蛋白尿。在eGFR≥60 mL/min/1.73 m²的非糖尿病个体中，托匹司他使用者与非布司他使用者相比蛋白尿发生率的调整后HR为0.60（95%置信区间，0.40 - 0.91；p = 0.016）。在eGFR＜60 mL/min/1.73 m²和eGFR≥60 mL/min/1.73 m²的两组之间，未观察到eGFR变化有显著差异。
在eGFR≥60 mL/min/1.73 m²的非糖尿病个体中，托匹司他现用者发生蛋白尿的风险低于非布司他现用者。我们的研究结果表明，在预防eGFR≥60 mL/min/1.73 m²的非糖尿病个体蛋白尿方面，托匹司他可能比非布司他更有效。
