RENAL PROTECTIVE EFFECTS OF TOPIROXOSTAT AND FEBUXISTAT, NEWLY AVAILABLE XANTHINE OXIDASE INHIBITORS

Abstract

Objective: Control of uric acid level (UA) plays an important role in the protection of organs in hypertensive (HTN) patients. Newly usable xanthine oxidase inhibitors, febuxostat (FBX) and topiroxostat (TPX) are expected to lead to more reduction of organ damages. However, the effects of them in a clinical situation remain unclear. We hypothesized these drugs have different effects based on the difference in actionmechanism. To demonstrate the effects of FBX and TPX on renal functions and compare them between the drugs. Design and method: We retrospectively collected 252 HTN patients with hyperuricemia (HU) who newly received a prescription of FBX or TPX and continued 24 weeks. Those who had other uric acid-lowering drugs, diabetes mellitus or severe proteinuria were excluded. 252 Participants were divided into FBX (128 patients) and TPX (124 patients) groups matched for age and sex. The changes of uric acid (UA), blood pressure, eGFR (defined by Japanese Society of Nephrology) and urinary albumin-to-creatinine ratio (UACR) were evaluated between the baseline and the 24-week-treatment by FBX and TPX. Results: The almost baseline characteristics were not significantly different between both groups except the usage of renin-angiotensin inhibitors. Administration of FBX or TPX lowered UA significantly (p < 0.0001). Diastolic blood pressure was significantly reduced only in FBX group (BP129.3 ± 17.8/78.7 ± 12.4 mmHg to BP126.1 ± 16.3/76.2 ± 11.1 mmHg, p = 0.049) and urinary albumin-to-creatinine ratio (UACR) was significantly decreased only in TPX group (90.0 ± 336 mg/gCr to 48.9 ± 171 mg/gCr, p = 0.027), while UACR in FBX group was not reduced (113 ± 376 mg/gCr to 120 ± 488 mg/gCr). The eGFR in both FBX group and TPX group were significantly increased from 55.2 ± 15.0 to 56.8 ± 15.7 mL/min/1.73m2 (p = 0.0082) and from 57.3 ± 16.3 to 61.5 ± 16.3 mL/min/1.73m2 (p = 0.0002), respectively. In TPX and FBX groups, there were no significant differences in change of eGFR between patients using high and low amount of TPX and FBX, respectively. The all data were presented as means ± SD. Conclusions: Our current study revealed TPX and FBX could improve eGFR in HTN patients, and moreover, TPX could reduce UACR. TPX could be 1st-line choice in HTN patients with HU.