Allopurinol initiation and dose escalation does not appear to increase the risk for all-cause mortality in patients with chronic kidney disease (CKD), according to new study findings published in the Annals of Internal Medicine.

The PERL (Preventing Early Renal Loss in Diabetes) and CKD-FIX (Controlled trial of slowing of Kidney Disease progression From the Inhibition of Xanthine oxidase) trials indicated that allopurinol treatment was associated with a 2-fold increased risk for death in patients with CKD.

To gauge excess death risk, investigators of the current study performed a propensity-score matched analysis of 5277 allopurinol initiators and 5277 noninitiators from the 2009-2019 Health Improvement Network UK primary care database. Patients aged 40 to 89 years had diagnosed gout and stage 3 to 5 CKD with no kidney transplantation.

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In an intent-to-treat analysis, the all-cause mortality rate was 4.9 vs 5.8 per 100 person-years among allopurinol initiators and noninitiators, respectively, Guanghua Lei, MD, PhD, of Xiangya Hospital, Central South University in Hunan, China, and colleagues reported. Allopurinol initiation was associated with a significant 15% reduced risk for death over 5 years. Significantly lower mortality risks were also found in subgroup analyses of patients on treatment and newly diagnosed with gout.

In a trial emulation analysis, Dr Lei’s team found a 13% reduced mortality risk among patients achieving vs not achieving target serum uric acid levels less than 0.36 mmol/L. They also found a 12% lower mortality risk among patients with allopurinol dose escalation to 150 to 600 mg/d compared with no escalation. Neither result was statistically significant.

It is possible that other factors biased survival, according to the investigators. Frail and ill patients, for example, may have been less likely to initiate allopurinol or receive dose escalation. Patients achieving target serum urate levels may have had increased contact with health care providers.

“Our study found that neither allopurinol use, nor achieving target [serum uric acid] level with allopurinol, nor allopurinol dose escalation seem to increase mortality in participants with gout and concurrent CKD,” Dr Lei’s team concluded. “These findings provide empirical evidence that adopting current gout treatment guidelines does not seem to have a detrimental effect on mortality in patients with both gout and CKD.”


Wei J, Choi HK, Neogi T, et al. Allopurinol initiation and all-cause mortality among patients with gout and concurrent chronic kidney disease: a population-based cohort study. Ann Intern Med. Published online January 24, 2022. doi:10.7326/M21-2347