別嘌呤醇不能延緩慢性腎臟疾病的進展

別嘌呤醇不能延緩慢性腎臟疾病的進展

作者：

小柯機器人

發布時間：2020/6/28 13:58:16

澳大利亞喬治全球健康研究所Sunil V. Badve團隊分析了別嘌呤醇對慢性腎臟疾病進展的影響。該成果於2020年6月25日發表在《新英格蘭醫學雜誌》上。

血清尿酸水平升高與慢性腎臟疾病的進展有關。別嘌呤醇降低尿酸的治療是否可減緩有進展風險的慢性腎臟病患者的腎小球濾過率（eGFR）估計值的下降尚不清楚。

在這項隨機對照試驗中，研究組招募了369名3或4期慢性腎臟病患者，均無痛風史，尿白蛋白：肌酐比率超過265（白蛋白以毫克為單位，肌酐以克為單位），eGFR至少降低3.0 mL/min·1.73m²。將其隨機分組，其中185例接受別嘌呤醇治療，184例接受安慰劑治療。

最終共有363例患者納入主要結局評估，平均eGFR為31.7 mL/min·1.73m²，中位尿白蛋白：肌酐比率為716.9，平均尿酸水平為8.2 mg/dL。104周後，別嘌呤醇組和安慰劑組之間eGFR的變化無顯著差異。別嘌呤醇組的182例患者中有84例（46％）發生嚴重不良事件，安慰劑組的181例患者中有79例（44％）。

總之，對於患有慢性腎臟疾病且進展風險較高的患者，採用別嘌呤醇降低尿酸鹽治療，與安慰劑相比，並不能減緩eGFR的下降。

附：英文原文

Title: Effects of Allopurinol on the Progression of Chronic Kidney Disease

Author: Sunil V. Badve, Ph.D.,, Elaine M. Pascoe, M.Biostat.,, Anushree Tiku, M.B., B.S.,, Neil Boudville, D.Med.,, Fiona G. Brown, Ph.D.,, Alan Cass, Ph.D.,, Philip Clarke, Ph.D.,, Nicola Dalbeth, M.D.,, Richard O. Day, M.D.,, Janak R. de Zoysa, M.B., Ch.B.,, Bettina Douglas, M.N.,, Randall Faull, Ph.D.,, David C. Harris, M.D.,, Carmel M. Hawley, M.Med.Sci.,, Graham R.D. Jones, D.Phil.,, John Kanellis, Ph.D.,, Suetonia C. Palmer, Ph.D.,, Vlado Perkovic, Ph.D.,, Gopala K. Rangan, Ph.D.,, Donna Reidlinger, M.P.H.,, Laura Robison, B.Sc.,, Robert J. Walker, M.D.,, Giles Walters, M.D.,, and David W. Johnson, Ph.D.

Issue&Volume: 2020-06-24

Abstract: Abstract

Background

Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known.

Methods

In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation.

Results

Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, 4.11 to 2.55] and 3.23 ml per minute per 1.73 m2 per year [95% CI, 3.98 to 2.47], respectively; mean difference, 0.10 ml per minute per 1.73 m2 per year [95% CI, 1.18 to 0.97]; P=0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group.

Conclusions

In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo.

DOI: 10.1056/NEJMoa1915833

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1915833