#838 Comparison of the incidence of proteinuria and eGFR change between febuxostat and topiroxostat users
Authors: Nakayama Shingo , Satoh Michihiro , Toyama Maya , Hashimoto Hideaki , Murakami Takahisa , Hirose Takuo , Obara Taku , Mori Takefumi , Metoki Hirohito 
Published: May 2024

Abstract

Background and Aims
Febuxostat and topiroxostat are novel non-purine selective xanthine oxidoreductase (XOR) inhibitors, commonly available for the treatment of hyperuricemia in Japan. The previous studies suggested that febuxostat and topiroxostat might have renoprotective effects. It is important to compare febuxostat with topiroxostat on the renoprotective effects for the selection of the XOR inhibitors in clinical settings. However, comparative data between febuxostat and topiroxostat on renal function and proteinuria are limited. Therefore, the present study aimed to compare renal function and proteinuria between febuxostat and topiroxostat.

Method
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) without estimated glomerular filtration rate (eGFR) &lt;30 mL/min/1.73 m2, a history of cardiovascular disease and proteinuria at baseline. The claims database includes all inpatient, outpatient, and pharmacy claims received from insurers during the study period. The use of febuxostat and topiroxostat was defined as having claims of dispensing (or prescribing) febuxostat and topiroxostat within 1 year before the baseline health check-up, respectively. Analyses were performed for the individuals with eGFR &lt;60 mL/min/1.73 m2 and those with eGFR ≥60 mL/min/1.73 m2 separately. The Cox proportional hazard model was used to assess the adjusted hazard ratio (HR) for the incidence of proteinuria in the topiroxostat users compared with the febuxostat users. We calculated the annual rate of eGFR change as the slope of the linear regression between eGFR and year for each participant. Changes in eGFR were compared between the febuxostat users and the topiroxostat users using multiple regression analysis. We performed stratified analyses according to sex, age (&lt;75 and ≥75 years), body mass index (BMI) (&lt;25 and ≥25 kg/m2), hypertension, and diabetes mellitus. Covariates included sex, age, BMI, current smoker, current drinker, diabetes mellitus, dyslipidemia, systolic blood pressure, use of angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, dihydropyridine calcium channel blocker, or the other antihypertensive drugs, serum uric acid level, and baseline eGFR.

Results
During a mean follow-up of 1.79 years, 1,433 participants developed proteinuria. In the non-diabetic individuals with eGFR ≥60 mL/min/1.73 m2, the fully adjusted HRs (95% confidence interval, p-value) for the incidence of proteinuria in the topiroxostat users compared with in the febuxostat users were 0.60 (0.40–0.91, p= 0.016). We found a significant interaction between diabetes mellitus and the use of topiroxostat on the incidence of proteinuria. No significant differences were observed in eGFR change between the two treatment groups with eGFR &lt;60 and ≥60 mL/min/1.73 m2. When we evaluated the eGFR change between the two groups with eGFR &lt;60 and ≥60 mL/min/1.73 m2 using the eGFRCKD-EPI, we found no significant differences in eGFR change between the two groups with eGFR &lt;60 and ≥60 mL/min/1.73 m2.

Conclusion
The topiroxostat prevalent-users had a lower risk of the incidence of proteinuria than the febuxostat prevalent-users in the non-diabetic individuals with eGFR ≥60 mL/min/1.73 m2. Our findings suggested that topiroxostat might be more effective than febuxostat in preventing proteinuria in non-diabetic individuals with eGFR ≥60 mL/min/1.73 m2.