• Sunil V Badve, Elaine M Pascoe, Anushree Tiku, Neil Boudville, Fiona G Brown, Alan Cass, Philip Clarke, Nicola Dalbeth, Richard O Day, Janak R de Zoysa, Bettina Douglas, Randall Faull, David C Harris, Carmel M Hawley, Jones Graham R D GRD From the Department of Renal Medicine, St. George Hospital (S.V.B., A.T.), the Renal and Metabolic Division, George Institute for Global Health (S.V., John Kanellis, Suetonia C Palmer, Vlado Perkovic, Gopala K Rangan, Donna Reidlinger, Laura Robison, Robert J Walker, Giles Walters, David W Johnson, and CKD-FIX Study Investigators.
• From the Department of Renal Medicine, St. George Hospital (S.V.B., A.T.), the Renal and Metabolic Division, George Institute for Global Health (S.V.B., A.T., V.P.), and St. Vincent's Clinical School (R.O.D., G.R.D.J.), University of New South Wales Medicine, the Departments of Clinical Pharmacology and Toxicology (R.O.D.) and Chemical Pathology, SydPath (G.R.D.J.), St. Vincent's Hospital, the Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney (D.C.H., G.K.R.), the Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District (D.C.H., G.K.R.), and the Department of Nephrology, the Royal North Shore Hospital (V.P.), Sydney, the Australasian Kidney Trials Network, University of Queensland (S.V.B., E.M.P., N.B., C.M.H., D.R., L.R., D.W.J.), the Department of Nephrology, Princess Alexandra Hospital, (B.D., C.M.H., D.W.J.), and the Translational Research Institute (D.W.J.), Brisbane, QLD, the Medical School, University of Western Australia, Perth (N.B.), the Department of Nephrology, Monash University at Monash Medical Centre, Melbourne, VIC (F.G.B., J.K.), Menzies School of Health Research, Charles Darwin University, Darwin, NT (A.C.), the University of Adelaide and Central Northern Adelaide Renal and Transplantation Services, Adelaide, SA (R.F.), and the Australian National University Medical School and the Department of Nephrology, Canberra Hospital, Canberra, ACT (G.W.) - all in Australia; the Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom (P.C.); and the Department of Medicine, University of Auckland (N.D., J.R.Z.), and the Renal Service, Waitemata District Health Board (J.R.Z.), Auckland, the Department of Medicine, University of Otago Christchurch, Christchurch (S.C.P.), and Dunedin School of Medicine, University of Otago, Dunedin (R.J.W.) - all in New Zealand.
• N. Engl. J. Med. 2020 Jun 25; 382 (26): 2504-2513.

BackgroundElevated 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.MethodsIn 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.ResultsEnrollment 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.ConclusionsIn 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.).Copyright © 2020 Massachusetts Medical Society.

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