Medication prescribed to one in five patients with chronic kidney disease is ineffective, according to a major clinical trial.
Allopurinol does not prevent worsening kidney disease: even though up to 20 percent of kidney disease patients receive the medication, the results of a major clinical trial have revealed.
Researchers from UNSW and the George Institute for Global Health collaborated with researchers from the Australian Kidney Trials Network to conduct a two-year trial, the CKD-FIX Study, at 31 hospitals in Australia and New Zealand. They enrolled 369 patients with chronic kidney disease who were considered to be at increased risk for further progression in the trial.
The results were published on June 25, 2020 in the New England Journal of Medicine, one of the most prestigious medical journals in the world.
The researchers compared the use of allopurinol, a medicine commonly used to reduce urate levels in the blood (also known as uric acid) – to a placebo and found that there was no difference in the rate of decline in kidney function.
“We found that kidney function decreased at a similar rate in patients who received allopurinol and those who received placebo,” says study co-leader Sunil Badve, joint associate professor of medicine at UNSW and principal investigator at the George Institute for Global Health.
“Our findings have important implications: One in five people with chronic kidney disease is taking medications such as allopurinol to reduce elevated levels of urate in the blood. We now know that they are probably taking medications that do not benefit them, unless they have other conditions. against which allopurinol is effective, like gout. “
Allopurinol can have side effects, such as severe allergic reactions and skin rashes. The researchers say it is important that people taking allopurinol to reduce blood urate levels do not abruptly stop treatment, but they first discussed this with a doctor.
Currently available treatment options to delay the progression of chronic kidney disease are limited and only partially effective.
“There is a great need for new treatments for this condition,” says A / Prof Badve.
“We chose allopurinol, a medication originally developed to treat gout, for our trial because it is commonly prescribed to reduce patients’ blood urate levels, a waste product created by the body’s metabolism.
“High levels of urate in the blood are associated with an increased risk of chronic kidney disease: approximately 70-75% of people with chronic kidney disease have elevated levels of urate in the blood.
“However, until our study we did not know whether the reduction in blood urate levels through that drug actually slowed the progression of chronic kidney disease.”
A / Prof Badve says the results indicate that the widely held opinion that elevated blood urate levels were responsible for the rapid decline in kidney function was probably incorrect.
“Based on our results, it appears that elevated blood urate levels are more likely indicator reduced kidney function, instead of why,” he says.
Professor Sean Emery, Senior Vice Dean for Research and Operations at UNSW Medicine, says: “Independent academic research through coordinated networks is critical to changing health outcomes. The work published today led by Professor Badve highlights the importance of using collaborative research networks to reveal important and significant findings. In this case, we now know that routine nephrology intervention can no longer be justified. Clinical practice will now change globally. “
Approximately 1.7 million Australians over the age of 18 have chronic kidney disease. Some of these people are at increased risk for further decline in kidney function, also known as progression of chronic kidney disease, to the point of needing dialysis or a kidney transplant. More than 3,000 Australians develop kidney failure requiring dialysis each year and there are currently more than 13,000 Australians on dialysis.
Reference: “Effects of allopurinol on the progression of chronic kidney disease” by Sunil V. Badve, Ph.D., Elaine M. Pascoe, M.Biostat., Anushree Tiku, MB, BS, Neil Boudville, D.Med. , Fiona G. Brown, Ph.D., Alan Cass, Ph.D., Philip Clarke, Ph.D., Nicola Dalbeth, MD, Richard O. Day, MD, Janak R. de Zoysa, MB, Ch.B . , Bettina Douglas, MN, Randall Faull, Ph.D., David C. Harris, MD, Carmel M. Hawley, M.Med.Sci., Graham RD Jones, D.Phil., John Kanellis, Ph.D., Suetonia C. Palmer, Ph.D., Vlado Perkovic, Ph.D., Gopala K. Rangan, Ph.D., Donna Reidlinger, MPH, Laura Robison, B.Sc., Robert J. Walker, MD, Giles Walters , MD, and David W. Johnson, Ph.D. for the researchers of the CKD-FIX study, June 25, 2020, New England Journal of Medicine.
DOI: 10.1056 / NEJMoa1915833
The CKD-FIX study was sponsored by the University of Queensland and coordinated by the Australian Kidney Trials Network. Professor David Johnson, Medical Director of the Queensland Kidney Transplant Service, was Chairman of the Trial Steering Committee and, in New Zealand, Dr. Janak de Zoysa of the Waitemata District Board of Health led the trial.
The study was funded by research grants from the Australian National Council for Health and Medical Research and the New Zealand Health Research Council and involved five UNSW researchers: Joint Associate Professor Sunil Badve, Dean of Medicine Professor Vlado Perkovic , Professor Ric Day, Joint Associate Professor Graham Jones and Joint Associate Professor Dr. Anushree Tiku. The full study is available at New England Journal of Medicine.