Akimoto Tetsu, Morishita Yoshiyuki, Ito Chiharu, Iimura Osamu, Tsunematsu Sadao, Watanabe Yuko, Kusano Eiji, Nagata Daisuke
Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan. ; Green Town Clinic, Tochigi, Japan.
Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan. ; Kumakura Clinic, Tochigi, Japan. ; Yuki Clinic, Ibaraki, Japan.
Drug Target Insights. 2014 Aug 13;8:39-43. doi: 10.4137/DTI.S16524. eCollection 2014.
Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD.
非布司他是一种非嘌呤类黄嘌呤氧化酶（XO）抑制剂，最近已获得上市批准。然而，关于晚期慢性肾脏病（CKD）患者使用该药物的经验信息有限。在本研究中，我们调查了口服非布司他对晚期CKD合并无症状高尿酸血症患者的影响。我们首次证明，非布司他治疗6个月后，不仅血清尿酸（UA）水平显著降低，而且氧化应激标志物8-羟基脱氧鸟苷的水平也显著降低，且无不良事件发生。这些结果促使我们进一步研究在晚期CKD患者中通过非布司他降低血清UA水平，同时通过阻断XO减轻氧化应激的临床影响。对更多受试者进行更详细的研究，并评估年龄、性别和饮食习惯等影响高尿酸血症的多种因素的作用，将有助于阐明在不同阶段CKD患者中治疗无症状高尿酸血症的治疗挑战。
