Ishii Takeo, Seya Nodoka, Taguri Masataka, Wakui Hiromichi, Yoshimura Ashio, Tamura Kouichi
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Nephrology, Yokohama Daiichi Hospital Zenjinkai, Yokohama, Japan.
Kidney Med. 2024 Aug 28;6(11):100896. doi: 10.1016/j.xkme.2024.100896. eCollection 2024 Nov.
RATIONALE & OBJECTIVE: Allopurinol and febuxostat, which are xanthine oxidoreductase inhibitors, have been widely used as uric acid-lowering medications. However, evidence regarding their cardiovascular effects in hemodialysis is insufficient. This study compared the effects of allopurinol and febuxostat on mortality and cardiovascular outcomes in patients receiving hemodialysis.
A retrospective observational cohort study.
SETTING & PARTICIPANTS: Data of 6,791 patients who had no history of topiroxostat usage and underwent maintenance hemodialysis between March 2016 and March 2019 at Yokohama Daiichi Hospital, Zenjinkai, and its affiliated dialysis clinics in Japan's Kanagawa and Tokyo metropolitan areas were collected.
Allopurinol, febuxostat, and nontreatment.
All-cause mortality, cardiovascular disease (CVD) events, heart failure (HF), acute myocardial infarction (AMI), and stroke.
For the main analyses, marginal structural Cox proportional hazards models were used to estimate HRs adjusted for time-varying confounding and selection bias because of censoring.
Allopurinol and febuxostat showed significantly better survival than nontreatment for all-cause mortality (HR, 0.40; 95% CI, 0.30-0.54 and HR, 0.49; 95% CI, 0.38-0.63, respectively), without significant difference between allopurinol and febuxostat. Allopurinol showed significantly better survival than nontreatment, whereas febuxostat did not for CVD events (HR, 0.89; 95% CI, 0.84-0.95 and HR, 1.01; 95% CI, 0.96-1.07, respectively), HF (HR, 0.71; 95% CI, 0.56-0.90 and HR, 1.03; 95% CI, 0.87-1.21, respectively), and AMI (HR, 0.48; 95% CI, 0.25-0.91 and HR, 0.76; 95% CI, 0.49-1.19, respectively). No comparisons showed significant results for stroke.
The ratio of renal or intestinal excretion of uric acid and uremic toxins could not be elucidated, and we could not investigate gene polymorphism because of the large number of cases.
Allopurinol and febuxostat improved survival for all-cause mortality. Allopurinol and not febuxostat reduced the risk of CVD events, HF, and AMI.
别嘌醇和非布司他作为黄嘌呤氧化还原酶抑制剂，已被广泛用作降尿酸药物。然而，关于它们在血液透析中的心血管效应的证据并不充分。本研究比较了别嘌醇和非布司他对接受血液透析患者的死亡率和心血管结局的影响。
一项回顾性观察性队列研究。
收集了2016年3月至2019年3月期间在日本神奈川县和东京都市区的横滨第一医院、全人会及其附属透析诊所接受维持性血液透析且无托匹司他使用史的6791例患者的数据。
别嘌醇、非布司他和未治疗。
全因死亡率、心血管疾病（CVD）事件、心力衰竭（HF）、急性心肌梗死（AMI）和中风。
在主要分析中，采用边际结构Cox比例风险模型来估计因时间变化的混杂因素和删失导致的选择偏倚而调整后的风险比（HR）。
在全因死亡率方面，别嘌醇和非布司他的生存率均显著优于未治疗组（HR分别为0.40；95%CI为0.30 - 0.54和HR为0.49；95%CI为0.38 - 0.63），别嘌醇和非布司他之间无显著差异。在CVD事件方面，别嘌醇的生存率显著优于未治疗组，而非布司他则不然（HR分别为0.89；95%CI为0.84 - 0.95和HR为1.01；95%CI为0.96 - 1.07）；在HF方面（HR分别为0.71；95%CI为0.56 - 0.90和HR为1.03；95%CI为0.87 - 1.21）以及AMI方面（HR分别为0.48；95%CI为0.25 - 0.91和HR为0.76；95%CI为0.49 - 1.19）亦是如此。对于中风，所有比较均未显示出显著结果。
无法阐明尿酸和尿毒症毒素的肾排泄或肠道排泄比例，且由于病例数量众多，无法研究基因多态性。
别嘌醇和非布司他可改善全因死亡率的生存率。别嘌醇而非非布司他可降低CVD事件、HF和AMI的风险。
