Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/126926
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Type: Journal article
Title: Effects of allopurinol on the progression of chronic kidney disease
Author: Badve, S.
Pascoe, E.
Tiku, A.
Boudville, N.
Brown, F.
Cass, A.
Clarke, P.
Dalbeth, N.
Day, R.
de Zoysa, J.
Douglas, B.
Faull, R.
Harris, D.
Hawley, C.
Jones, G.
Kanellis, J.
Palmer, S.
Perkovic, V.
Rangan, G.
Reidlinger, D.
et al.
Citation: The New England journal of medicine, 2020; 382(26):2504-2513
Publisher: Massachusetts Medical Society
Issue Date: 2020
ISSN: 0028-4793
1533-4406
Statement of
Responsibility: 
Sunil V. Badve, Elaine M. Pascoe, Anushree Tiku, Neil Boudville, Fiona G. Brown ... Randall Faull ... et al.
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. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932. opens in new tab.)
Keywords: CKD-FIX Study Investigators; Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 1; Disease Progression; Allopurinol; Uric Acid; Xanthine Oxidase; Gout Suppressants; Enzyme Inhibitors; Glomerular Filtration Rate; Treatment Failure; Double-Blind Method; Renin-Angiotensin System; Aged; Middle Aged; Female; Male; Renal Insufficiency, Chronic
Rights: © 2020 Massachusetts Medical Society.
RMID: 1000023344
DOI: 10.1056/NEJMoa1915833
Grant ID: http://purl.org/au-research/grants/nhmrc/1043203
Appears in Collections:Medicine publications

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