Background/Purpose: Chronic kidney disease (CKD) is a cause and consequence of hyperuricemia. While clinicians are often cautious about using allopurinol in patients with CKD, there is emerging evidence that urate-lowering therapy (ULT) may be beneficial in subjects with renal dysfunction. Whether patients with gout may experience less CKD with allopurinol is not clear.

Methods: We conducted a cohort study in The Health Improvement Network (THIN), which is a general practitioner electronic medical records database representative of the UK general population. We included subjects aged 18-89 with incident gout between 01/01/2000-12/31/2014 who had had at least 1 GP contact in the year prior to study entry. We excluded individuals with CKD stage ≥3 prior to gout diagnosis. We identified allopurinol initiators after their incident gout diagnosis. We computed propensity scores (PS) to minimize effects of confounding by indication using logistic regression, with incident allopurinol use as the dependent variable and potential confounders that reflect indication for allopurinol use and/or risk of CKD (table) as the independent variables. Each incident allopurinol user was matched 1:1 with an unexposed subject with greedy matching using the PS within 1-year cohort accrual blocks. Follow-up started from the index date (date of 1^stallopurinol prescription for the exposed, and randomly assigned date for the unexposed within the one-year accrual block), and continued until CKD stage ≥3, death, or end of study. The relation of incident allopurinol use among subjects with incident gout to development of CKD ≥3 was assessed using Cox proportional hazard models. Since allopurinol initiators may stop using allopurinol or non-users may start using allopurinol during the follow-up period, we performed a sensitivity analysis in which subjects were censored if their exposure status changed.

Results: There were 13,727 allopurinol initiators who were PS-matched with 13,727 non-users, among whom 1401 and 1319, respectively, developed CKD stage ≥3, with mean follow-up time of 4 years for both groups. Overall, covariates were well-balanced in the two groups, with mean age of 58 years and mean BMI of 30 kg/m². Allopurinol use was not associated with an increased risk of developing CKD ≥3 compared with non-users, with a hazards ratio (HR) of 1.05 (95% CI 0.97-1.13). When additionally adjusted for the potential confounders included in the original PS model, the effect estimate remained unchanged (table). In the sensitivity analysis the adjusted HR did not change materially (HR=1.04, 95% CI 0.96-1.14).

Conclusion: In this large cohort, the prescription of allopurinol was not associated with increased risk of renal function deterioration. This is an important message for health care providers, highlighting that therapy for gout with allopurinol should not have a harmful effect on renal function.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/no-increased-risk-of-chronic-kidney-disease-with-allopurinol-use/