Horino Taro, Hatakeyama Yutaka, Ichii Osamu, Matsumoto Tatsuki, Shimamura Yoshiko, Inoue Kosuke, Terada Yoshio, Okuhara Yoshiyasu
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
Center of Medical Information Science, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
Clin Exp Nephrol. 2018 Apr;22(2):337-345. doi: 10.1007/s10157-017-1452-3. Epub 2017 Jul 27.
Hyperuricemia is associated with chronic kidney disease (CKD). Although topiroxostat, a novel, non-purine, selective xanthine oxidase inhibitor, has a strong effect against hyperuricemia, limited data are available on its renoprotective effect against CKD.
This study was conducted between October 2014 and May 2016. Thirty patients (20 male, 10 female) were administered 40 mg/day of topiroxostat twice daily. All patients were followed for a year. To elucidate the effects of topiroxostat, we evaluated the clinically documented primary indication of progression, viz. laboratory evidence of kidney function decline (reference indicator), uric acid, and hypertension in different patient groups, separated according to their baseline uProt levels and baseline eGFR.
Topiroxostat treatment resulted in significant reduction in SUA (-1.53 mg/dL), systolic blood pressure (-8.9 mmHg), diastolic blood pressure (-5.0 mmHg), and urinary protein excretion (-795.5 mg/gCr) compared with baseline values. However, serum creatinine and urinary NAG levels, and estimated glomerular filtration rate did not change significantly.
Topiroxostat reduced SUA levels effectively and may exhibit renoprotective effect in hyperuricemic patients with CKD. Further studies are required to clarify whether topiroxostat prevents the progression of renal disease and improves the prognosis of CKD patients.
高尿酸血症与慢性肾脏病（CKD）相关。尽管托匹司他是一种新型非嘌呤选择性黄嘌呤氧化酶抑制剂，对高尿酸血症有强效作用，但其对CKD的肾脏保护作用的数据有限。
本研究于2014年10月至2016年5月进行。30例患者（20例男性，10例女性）每日两次服用40mg托匹司他。所有患者随访一年。为阐明托匹司他的作用，我们评估了临床记录的疾病进展的主要指标，即肾功能下降的实验室证据（参考指标）、尿酸以及根据基线尿蛋白水平和基线估算肾小球滤过率分组的不同患者组中的高血压情况。
与基线值相比，托匹司他治疗使血清尿酸（SUA）显著降低（-1.53mg/dL）、收缩压（-8.9mmHg）、舒张压（-5.0mmHg）和尿蛋白排泄（-795.5mg/gCr）降低。然而，血清肌酐和尿NAG水平以及估算肾小球滤过率没有显著变化。
托匹司他有效降低SUA水平，可能对高尿酸血症合并CKD患者具有肾脏保护作用。需要进一步研究以阐明托匹司他是否能预防肾脏疾病进展并改善CKD患者的预后。
