24 Jun Does Lowering Uric Acid with Allopurinol Slow Progression of Chronic Kidney Disease?
MedicalResearch.com Interview with:
Sunil Badve MBBS, MD, DNB, FRACP, PhD, FASN
Staff specialist nephrologist | St George Hospital
Conjoint Associate Professor | University of New South Wales
Senior Research Fellow, Acute Kidney Injury and Trials
The George Institute for Global Health
MedicalResearch.com: What is the background for this study?
Response: Elevated serum urate levels are associated with progression of chronic kidney disease (CKD). CKD patients often have elevated serum urate levels due to decreased excretion.
We conducted this placebo-controlled randomized trial to evaluate if urate-lowering treatment with allopurinol would attenuate decline in estimated glomerular filtration rate (eGFR) over 2 years in patients with CKD. We enrolled 369 CKD patients with high progression risk and no prior history of gout.
MedicalResearch.com: What are the main findings?
Response: The results showed that despite a sustained mean reduction of 35% in serum urate levels, compared with placebo, treatment with allopurinol did not result in slower eGFR decline. Furthermore, we did not observe a greater decrease in proteinuria, blood pressure, or the risk of the composite kidney outcome of a decline in the eGFR (when either a 40% or a 30% decline from baseline was used), end-stage kidney disease, or death in association with allopurinol.
MedicalResearch.com: What should readers take away from your report?
Response: Urate-lowering treatment with allopurinol is not indicated to prevent progression in CKD. Our results do not appear to support the view that circulating urate levels play a causal role in the progression of chronic kidney disease. Evidence from observational studies shows only an association between urate levels and progression of chronic kidney disease, not a cause-and-effect relationship. Such treatment should be reserved only for specific clinical indications, such as gout.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: As suggested by a scientific workshop organized by the National Kidney Foundation of the United States in September 2016, further trials are required to assess the effects of urate-lowering treatment on kidney outcomes in general population, who do not have kidney disease or have early stages of CKD.
MedicalResearch.com: Is there anything else you would like to add?
Response: Our results are complementary to the PERL and FEATHER trials. The totality of evidence suggests that urate-lowering therapy does not prevent progression of CKD. The CKD-FIX trial was supported by project grants from the National Health and Medical Research Council of Australia and Health Research Council of New Zealand.
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., for the CKD-FIX Study Investigators
June 25, 2020
N Engl J Med 2020; 382:2504-2513
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