Stamp of reassurance for allopurinol in gout + CKD

3 minute read

A large study found a lower mortality rate among gout patients with chronic kidney disease treated with allopurinol compared to those not treated with it.

Doubts about the safety of allopurinol in patients with concurrent chronic kidney disease and gout may have been laid to rest with a study finding no increase in all-cause mortality – and even a possible decrease – associated with the drug in this group.

A paper published in the Annals of Internal Medicine described the outcomes of a retrospective population-based study involving 5277 adults with gout and moderate-to-severe chronic kidney disease who were initiated on allopurinol, and the same number of propensity-matched individuals not on allopurinol.

Five years after starting allopurinol, the study found the mortality rate was actually a significant 15% lower among patients treated with allopurinol compared to those who were never treated with it.

The study also created two simulated randomised controlled trials using the same patient data, to examine whether patients who achieved a specific urate target or those who had their dose of allopurinol escalated over time had any difference in mortality with those who didn’t achieve that target or didn’t have dose-escalation.

Again, the study found no significant differences in mortality at five years between those who achieved a serum urate target and those who didn’t, or those who had dose escalation and those who didn’t.

The questions about allopurinol stemmed from two randomised controlled trials published in 2020, both involving patients with chronic kidney disease but not gout, which found a doubling of mortality in those treated with allopurinol.

However, rheumatologists have been cautious in accepting those earlier findings, says Professor Peter Youssef, clinical professor at Royal Prince Alfred Hospital and Sydney University. The two previous studies were investigating whether lowering serum urate might have renal or cardiac benefits or prevented progression of kidney disease, but excluded people with gout.

This new study not only included people with gout but propensity-matched the control group to ensure the two arms were balanced in their overall risk factors and comorbidities.

“I think it’s a stamp of reassurance for allopurinol in patients with gout,” he said. “If you’ve got gout and chronic kidney disease, not only is allopurinol safe, not only is mortality not increased but there may be a reduction in mortality.”

Professor Youssef also pointed out that people with gout and chronic kidney disease – which represents around one fifth of gout patients – have generally been undertreated because of concerns about the risk of toxicity with allopurinol. However, this study included a range of dosages, from 100 mg/d to 900 mg/d, and there was no increased mortality even among those who had escalation of their allopurinol dose.

Ann Intern Med 2022, online 25 January

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