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Title: | Effects of allopurinol on the progression of chronic kidney disease. | Authors: | Clarke P.;Dalbeth N.;Day R.O.;De Zoysa J.R.;Douglas B.;Perkovic V.;Rangan G.K.;Reidlinger D.;Robison L.;Walker R.J.;Walters G.;Johnson D.W.;Badve S.V.;Pascoe E.M.;Tiku A.;Boudville N.;Brown F.G.;Cass A.;Faull R.;Harris D.C.;Hawley C.M.;Jones G.R.D.;Kanellis J.;Palmer S.C. | Institution: | (Badve, Tiku) Department of Renal Medicine, St. George Hospital, Australia (Badve, Tiku, Perkovic) Renal and Metabolic Division, George Institute for Global Health, Australia (Day, Jones) St. Vincent's Clinical School, University of New South Wales Medicine, Australia (Day) Department of Clinical Pharmacology and Toxicology, SydPath, Australia (Day) Department of Chemical Pathology, SydPath, Australia (Jones) St. Vincent's Hospital, Centre for Transplant and Renal Research, Australia (Harris, Rangan) Westmead Institute for Medical Research, University of Sydney, Australia (Harris, Rangan) Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Australia (Perkovic) Department of Nephrology, Royal North Shore Hospital, Sydney, Australia (Badve, Pascoe, Boudville, Hawley, Reidlinger, Robison, Johnson) Australasian Kidney Trials Network, University of Queensland, Australia (Douglas, Hawley, Johnson) Department of Nephrology, Princess Alexandra Hospital, Australia (Johnson) Translational Research Institute, Brisbane, QLD, Australia (Boudville) Medical School, University of Western Australia, Perth, Australia (Brown, Kanellis) Department of Nephrology, Monash University, Monash Medical Centre, Melbourne, VIC, Australia (Cass) Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia (Faull) University of Adelaide, Central Northern Adelaide Renal and Transplantation Services, Adelaide, SA, Australia (Walters) Australian National University Medical School, Department of Nephrology, Canberra Hospital, Canberra, ACT, Australia (Clarke) Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom (Dalbeth, De Zoysa) Department of Medicine, University of Auckland, New Zealand (De Zoysa) Renal Service, Waitemata District Health Board, Auckland, New Zealand (Palmer) Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand (Walker) Dunedin School of Medicine, University of Otago, Dunedin, New Zealand | Issue Date: | 30-Sep-2020 | Copyright year: | 2020 | Publisher: | Massachussetts Medical Society | Place of publication: | United States | Publication information: | New England Journal of Medicine. 382 (26) (pp 2504-2513), 2020. Date of Publication: 25 Jun 2020. | Journal: | New England Journal of Medicine | 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. METHOD(S): 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. RESULT(S): 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. CONCLUSION(S): 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.Copyright © 2020 Massachusetts Medical Society. | DOI: | http://monash.idm.oclc.org/login?url=http://acs.hcn.com.au/?acc=36265&url=http://dx.doi.org/10.1056/NEJMoa1915833 | PubMed URL: | 32579811 [http://www.ncbi.nlm.nih.gov/pubmed/?term=32579811] | ISSN: | 0028-4793 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/29054 | Type: | Article | Type of Clinical Study or Trial: | Randomised controlled trial |
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