澳大利亚乔治全球健康研究所Sunil V. Badve团队分析了别嘌呤醇对慢性肾脏疾病进展的影响。该成果于2020年6月25日发表在《新英格兰医学杂志》上。

血清尿酸水平升高与慢性肾脏疾病的进展有关。别嘌呤醇降低尿酸的治疗是否可减缓有进展风险的慢性肾脏病患者的肾小球滤过率（eGFR）估计值的下降尚不清楚。

在这项随机对照试验中，研究组招募了369名3或4期慢性肾脏病患者，均无痛风史，尿白蛋白：肌酐比率超过265（白蛋白以毫克为单位，肌酐以克为单位），eGFR至少降低3.0 mL/min·1.73m²。将其随机分组，其中185例接受别嘌呤醇治疗，184例接受安慰剂治疗。

最终共有363例患者纳入主要结局评估，平均eGFR为31.7 mL/min·1.73m²，中位尿白蛋白：肌酐比率为716.9，平均尿酸水平为8.2 mg/dL。104周后，别嘌呤醇组和安慰剂组之间eGFR的变化无显著差异。别嘌呤醇组的182例患者中有84例（46％）发生严重不良事件，安慰剂组的181例患者中有79例（44％）。

总之，对于患有慢性肾脏疾病且进展风险较高的患者，采用别嘌呤醇降低尿酸盐治疗，与安慰剂相比，并不能减缓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