Allopurinol and Progression of CKD and Cardiovascular Events: Long-term Follow-up of a Randomized Clinical Trial

• Published in: American journal of kidney diseases Vol. 65; no. 4; pp. 543 - 549
• Main Authors: Goicoechea, Marian, MD, PhD, Garcia de Vinuesa, Soledad, MD, Verdalles, Ursula, MD, Verde, Eduardo, MD, Macias, Nicolas, MD, Santos, Alba, MD, Pérez de Jose, Ana, MD, PhD, Cedeño, Santiago, MD, Linares, Tania, MD, Luño, Jose, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2015
• Subjects: Aged; Aged, 80 and over; Allopurinol - pharmacology; Allopurinol - therapeutic use; allopurinol treatment; cardiovascular (CV) risk; Cardiovascular Diseases - epidemiology; Chronic kidney disease (CKD) progression; Creatinine - blood; Disease Progression; Female; Follow-Up Studies; Glomerular Filtration Rate - drug effects; Gout Suppressants - pharmacology; Gout Suppressants - therapeutic use; Humans; hyperuricemia; Incidence; Longitudinal Studies; Male; Middle Aged; Nephrology; renal disease; Renal Insufficiency, Chronic - drug therapy; Renal Insufficiency, Chronic - mortality; Risk Factors; Treatment Outcome; Uric Acid - blood; uric acid concentration; hyperuricemia; cardiovascular (CV) risk; uric acid concentration; Chronic kidney disease (CKD) progression; allopurinol treatment; renal disease
• ISSN: 0272-6386; 1523-6838
• DOI: 10.1053/j.ajkd.2014.11.016

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.