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. 2022 Apr;175(4):461-470.
doi: 10.7326/M21-2347. Epub 2022 Jan 25.

Allopurinol Initiation and All-Cause Mortality Among Patients With Gout and Concurrent Chronic Kidney Disease : A Population-Based Cohort Study

Jie Wei  1 , Hyon K Choi  2 , Tuhina Neogi  3 , Nicola Dalbeth  4 , Robert Terkeltaub  5 , Lisa K Stamp  6 , Houchen Lyu  7 , Natalie McCormick  8 , Jingbo Niu  9 , Chao Zeng  10 , Guanghua Lei  11 , Yuqing Zhang  2
Affiliations

Allopurinol Initiation and All-Cause Mortality Among Patients With Gout and Concurrent Chronic Kidney Disease : A Population-Based Cohort Study

Jie Wei et al. Ann Intern Med. 2022 Apr.

Abstract

Background: Two 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.

Objective: To 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.

Design: Cohort study.

Setting: The Health Improvement Network U.K. primary care database (2000 to 2019).

Participants: Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD.

Measurements: The 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.

Results: Mortality 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).

Limitation: Residual confounding cannot be ruled out.

Conclusion: In 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 source: Project Program of National Clinical Research Center for Geriatric Disorders.

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Figures

Appendix Figure 1.
Appendix Figure 1.
Flow chart of eligible persons for examining the relation of allopurinol initiation and allopurinol dose escalation to all-cause mortality, THIN 2000 to 2019. PS = propensity score; THIN = The Health Improvement Network.
Appendix Figure 2.
Appendix Figure 2.
Five-year risk for death between patients achieving target SU level and those not achieving target SU level with allopurinol in the target trial emulation study. SU = serum urate.
Appendix Figure 3.
Appendix Figure 3.
Five-year risk for death between allopurinol dose escalation and no allopurinol dose escalation in the target trial emulation study.
Figure 1.
Figure 1.
Flow chart of eligible persons for examining the relation of allopurinol initiation and achieving target SU level with allopurinol to all-cause mortality, THIN 2000 to 2019. PS= propensity score; SU= serum urate; THIN= The Health Improvement Network.
Figure 2.
Figure 2.
Five-year cumulative mortality between allopurinol initiators and noninitiators in the propensity score–matched study.
See this image and copyright information in PMC

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