Allopurinol, Febuxostat, and Nonuse of Xanthine Oxidoreductase Inhibitor Treatment in Patients Receiving Hemodialysis: A Longitudinal Analysis

IF 3.2 Q1 UROLOGY & NEPHROLOGY
Takeo Ishii , Nodoka Seya , Masataka Taguri , Hiromichi Wakui , Ashio Yoshimura , Kouichi Tamura
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引用次数: 0

Abstract

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.

Study Design

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.

Exposure

Allopurinol, febuxostat, and nontreatment.

Outcomes

All-cause mortality, cardiovascular disease (CVD) events, heart failure (HF), acute myocardial infarction (AMI), and stroke.

Analytical Approach

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.

Results

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.

Limitations

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.

Conclusions

Allopurinol and febuxostat improved survival for all-cause mortality. Allopurinol and not febuxostat reduced the risk of CVD events, HF, and AMI.

Plain Language Summary

Uric acid-lowering therapy has been used to prevent gout attacks and protect organs by reducing inflammation by lowering uric acid levels. However, uric acid-lowering medications have recently been found to have a side effect of inhibiting a channel responsible for excreting toxins, such as adenosine triphosphate-binding cassette transporter G2; the effects of medications with a strong inhibitory effect, such as febuxostat, are currently under investigation. Patients with kidney failure or dialysis excrete toxins through feces from their intestines in addition to removing toxins through dialysis. If uric acid-lowering medications suppress the channels responsible for intestinal toxin excretion, could this lead to the development of heart failure or stroke? This study investigated this question.
血液透析患者的别嘌醇、非布索坦和不使用黄嘌呤氧化还原酶抑制剂治疗:纵向分析
理由与amp; 目的别嘌醇和非布索坦是黄嘌呤氧化还原酶抑制剂,已被广泛用作降尿酸药物。然而,有关它们对血液透析患者心血管影响的证据尚不充分。本研究比较了别嘌醇和非布索坦对血液透析患者死亡率和心血管预后的影响。设置&amp; 参与者收集了2016年3月至2019年3月期间在日本神奈川和东京都的横滨第一医院、善进会及其附属透析诊所接受维持性血液透析的6791名无托吡索坦使用史的患者的数据。结果全因死亡率、心血管疾病(CVD)事件、心力衰竭(HF)、急性心肌梗死(AMI)和中风。分析方法在主要分析中,使用边际结构Cox比例危险模型估算HRs,并对时变混杂因素和由于人口普查造成的选择偏差进行调整。结果 在全因死亡率方面,别嘌醇和非布索坦的生存率明显优于未接受治疗者(HR,分别为0.40;95% CI,0.30-0.54和HR,0.49;95% CI,0.38-0.63),别嘌醇和非布索坦之间无明显差异。在心血管疾病事件(HR,0.89;95% CI,0.84-0.95 和 HR,1.01;95% CI,0.96-1.07)、HF(HR,0.49;95% CI,0.38-0.63)和HR(HR,0.49;95% CI,0.38-0.63)方面,别嘌醇的生存率明显优于未治疗者,而非布司他则不然。07)、HF(分别为HR,0.71;95% CI,0.56-0.90和HR,1.03;95% CI,0.87-1.21)和AMI(分别为HR,0.48;95% CI,0.25-0.91和HR,0.76;95% CI,0.49-1.19)。局限性无法阐明尿酸和尿毒症毒素的肾脏或肠道排泄比例,而且由于病例较多,我们无法研究基因多态性。别嘌醇而非布索坦可降低心血管疾病事件、高血压和急性心肌梗死的风险。白话摘要降尿酸疗法已被用于预防痛风发作,并通过降低尿酸水平减少炎症来保护器官。然而,最近发现降尿酸药物具有抑制负责排泄毒素的通道(如三磷酸腺苷结合盒转运体 G2)的副作用;目前正在研究具有强烈抑制作用的药物(如非布索坦)的效果。肾衰竭或透析患者除了通过透析清除毒素外,还会通过粪便从肠道排出毒素。如果降尿酸药物抑制了负责肠道毒素排泄的通道,是否会导致心力衰竭或中风的发生?本研究对这一问题进行了调查。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Kidney Medicine
Kidney Medicine Medicine-Internal Medicine
CiteScore
4.80
自引率
5.10%
发文量
176
审稿时长
12 weeks
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