Original Investigation
Pathogenesis and Treatment of Kidney Disease
Allopurinol and Progression of CKD and Cardiovascular Events: Long-term Follow-up of a Randomized Clinical Trial

https://doi.org/10.1053/j.ajkd.2014.11.016Get rights and content

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, 100 mg/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.

Section snippets

Study Design

The design of the previous randomized controlled trial (RCT) has been described elsewhere.1 Briefly, 113 patients with eGFRs < 60 mL/min/1.73 m2, stable clinical condition (no hospitalizations or cardiovascular events within the 3 months before screening), and stable kidney function were randomly assigned according to a computer-generated list to continue with their standard treatment (control group) or to treatment with allopurinol at 100 mg/d. The dosage of antihypertensive drugs, lipid-lowering

Patient Flow

Baseline characteristics, previous cardiovascular diseases, concomitant medication, and laboratory parameters have been described elsewhere1 and are listed in Table 1. In the original study, 113 participants (57 in the allopurinol group and 56 in the control group) initially were followed up for 2 years. In the long-term follow-up reported here, 107 participants were followed up to 5 additional years (56 in the allopurinol group because 1 patient was lost to follow-up and 51 in the control

Discussion

This post hoc intention-to-treat analysis of previously published study data shows that the beneficial effect of treatment with allopurinol on progression of kidney disease and cardiovascular risk was maintained in the long term.1 After a median follow-up of 7 years, allopurinol was shown to reduce the risk of renal events by 68% and the risk of cardiovascular events by 57%. Our study design is strengthened by the use of a renal end point that included initiation of dialysis therapy and

Acknowledgements

Support: None.

Financial Disclosure: The authors declare that they have no relevant financial interests.

Contributions: Research idea and study design: MG, SMGdV, JL; data acquisition: MG, SMGdV, UV, EV, NM, AS, APdJ, SC, TL; statistical analysis: MG, JL; supervision or mentorship: MG, SMGdV, LJ. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or

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