• Jie Wei, Hyon K Choi, Tuhina Neogi, Nicola Dalbeth, Robert Terkeltaub, Lisa K Stamp, Houchen Lyu, Natalie McCormick, Jingbo Niu, Chao Zeng, Guanghua Lei, and Yuqing Zhang.
• Health Management Center, Xiangya Hospital, Central South University, Changsha, China (J.W.).
• Ann. Intern. Med. 2022 Apr 1; 175 (4): 461470461-470.

BackgroundTwo recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown.ObjectiveTo examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD.DesignCohort study.SettingThe Health Improvement Network U.K. primary care database (2000 to 2019).ParticipantsPatients aged 40 years or older who had gout and concurrent moderate-to-severe CKD.MeasurementsThe association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators.ResultsMortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07).LimitationResidual confounding cannot be ruled out.ConclusionIn this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD.Primary Funding SourceProject Program of National Clinical Research Center for Geriatric Disorders.

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