Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial

Abstract

Background: Asymptomatic hyperuricemia increases renal and cardiovascular (CV) risk. We previously conducted a 2-year, single-blind, randomized, controlled trial of allopurinol treatment that showed improved estimated glomerular filtration rate and reduced CV risk.

Study design: Post hoc analysis of a long-term follow-up after completion of the 2-year trial.

Setting & participants: 113 participants (57 in the allopurinol group and 56 in the control group) initially followed up for 2 years and 107 participants followed up to 5 additional years.

Intervention: Continuation of allopurinol treatment, 100mg/d, or standard treatment.

Outcome: Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or ≥50% decrease in estimated estimated glomerular filtration rate) and CV events (defined as myocardial infarction, coronary revascularization or angina pectoris, congestive heart failure, cerebrovascular disease, and peripheral vascular disease).

Results: During initial follow-up, there were 2 renal and 7 CV events in the allopurinol group compared with 6 renal and 15 CV events in the control group. In the long-term follow-up period, 12 of 56 participants taking allopurinol stopped treatment and 10 of 51 control participants received allopurinol. During long-term follow-up, an additional 7 and 9 participants in the allopurinol group experienced a renal or CV event, respectively, and an additional 18 and 8 participants in the control group experienced a renal or CV event, respectively. Thus, during the initial and long-term follow-up (median, 84 months), 9 patients in the allopurinol group had a renal event compared with 24 patients in the control group (HR, 0.32; 95% CI, 0.15-0.69; P=0.004; adjusted for age, sex, baseline kidney function, uric acid level, and renin-angiotensin-aldosterone system blockers). Overall, 16 patients treated with allopurinol experienced CV events compared with 23 in the control group (HR, 0.43; 95% CI, 0.21-0.88; P=0.02; adjusted for age, sex, and baseline kidney function).

Limitations: Small sample size, single center, not double blind, post hoc follow-up and analysis.

Conclusions: Long-term treatment with allopurinol may slow the rate of progression of kidney disease and reduce CV risk.

Keywords: Chronic kidney disease (CKD) progression; allopurinol treatment; cardiovascular (CV) risk; hyperuricemia; renal disease; uric acid concentration.