Allopurinol, a frequently used gout medication, does not appear to drive up the risk for dying among gout patients who also struggle with chronic kidney disease, new research shows.
The finding is based on an analysis of two decades worth of British health records. And it may put to rest recent concerns regarding a well-known drug that both gout patients and kidney disease patients have used for decades to rein in harmfully high uric acid levels.
"Allopurinol is the most widely used urate-lowering medication," said study author Yuqing Zhang. He's a professor of medicine in residence with the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, in Boston.
The problem, said Zhang, is that two recent studies reported "that allopurinol was associated with a twofold increased risk [for death] in patients with renal [kidney] disease but without gout."
But in the new report, published Jan. 25 in the Annals of Internal Medicine, study author Jie Wei said that the researchers "found that allopurinol initiation was not associated with a higher mortality than non-allopurinol use in patients with gout and moderate-to-severe renal disease." Wei is an associate professor with the Health Management Center of Xiangya Hospital at Central South University in Changsha, China.
Gout is the most common type of inflammatory arthritis, the study team noted. It's characterized by high uric acid levels that, if left uncontrolled, are associated with the lightning-fast triggering of often excruciating and debilitating joint pain.
Allopurinol -- first approved for use by the U.S. Food and Drug Administration in 1966 -- is often prescribed as a cheap and effective way to control uric acid levels and prevent such attacks from happening in the first place.
Allopurinol can also be prescribed to chronic kidney disease patients as a way to slow down disease progression, the study authors said. In addition, about one in five gout patients -- many of whom take allopurinol on a daily basis -- have chronic kidney disease as well.
Still, the two studies published in 2020 in the New England Journal of Medicine rang alarm bells. The studies found no evidence that allopurinol helps to preserve kidney function among kidney patients who do not have gout. In addition, investigations unexpectedly uncovered what appeared to be a doubling of the risk for dying among kidney patients who took the medication.
To see whether a similar risk might exist among patients with both kidney disease and gout, Zhang's team analyzed electronic health records on nearly 5,300 British patients between the ages of 40 and 89. All had both gout and moderate-to-severe kidney disease.
After following the incidence of death over five-year tracking periods, the investigators determined there was no higher death risk among those who were just starting to take allopurinol. Nor was any elevated risk seen among those who had gotten their uric acid levels to their target goal by using allopurinol. Increasing allopurinol dosage was also found to be safe.
"Our findings are clinically relevant in gout care, and provide reassurance that allopurinol treatment does not have an apparent detrimental effect on mortality in patients with both gout and chronic kidney disease," Zhang said.
Howard Feinberg, a professor of rheumatology and assistant medical director at Touro University California, said this new study is one of many that have sought to weigh the pros and cons of a drug that has been a treatment mainstay for the last 55 years.
"There was fear early in its use that it would cause kidney damage," noted Feinberg, who was not involved with the study. "Recently, testing was done to see if it could prevent kidney damage. Neither of these proved true," he said.
"During these tests some of the patients died from their illnesses," he acknowledged, but "most tests showed that allopurinol did not change the risk of death from the illnesses suffered by these patients. In two research studies, when they looked at the patients who had died during the research, more of the patients taking allopurinol died. [But] there was no proof that this was because of the allopurinol. The numbers were very small and could easily be a coincidence."
Feinberg said coming to the conclusion that allopurinol is risky based solely on those earlier findings would be "just like seeing a lot of car accidents at the same spot may make you think it is a dangerous road, when it is really due to drunk drivers from the bar down the street."
His take: "There is so much information that shows that allopurinol is safe, and so little information showing a risk, this is not an important area for research. We can't research everything. There are many bigger risks to test."
There's more on allopurinol at the U.S. National Library of Medicine.
SOURCES: Yuqing Zhang, DSc, professor, medicine in residence, division of rheumatology, allergy and immunology, department of medicine, Massachusetts General Hospital and Harvard Medical School, Boston; Jie Wei, PhD, associate professor, Health Management Center, Xiangya Hospital, Central South University, Changsha, China; Howard Feinberg, DO, professor, rheumatology, associate dean, graduate medical education and program development, and assistant medical director, Touro University California, Mare Island, Vallejo, Calif.; Annals of Internal Medicine, March 2022