Effect of allopurinol in chronic kidney disease progression and cardiovascular risk

Abstract

Background and objectives: Hyperuricemia is associated with hypertension, inflammation, renal disease progression, and cardiovascular disease. However, no data are available regarding the effect of allopurinol in patients with chronic kidney disease.

Design, setting, participants, & measurements: We conducted a prospective, randomized trial of 113 patients with estimated GFR (eGFR) <60 ml/min. Patients were randomly assigned to treatment with allopurinol 100 mg/d (n = 57) or to continue the usual therapy (n = 56). Clinical, biochemical, and inflammatory parameters were measured at baseline and at 6, 12, and 24 months of treatment. The objectives of study were: (1) renal disease progression; (2) cardiovascular events; and (3) hospitalizations of any causes.

Results: Serum uric acid and C-reactive protein levels were significantly decreased in subjects treated with allopurinol. In the control group, eGFR decreased 3.3 +/- 1.2 ml/min per 1.73 m(2), and in the allopurinol group, eGFR increased 1.3 +/- 1.3 ml/min per 1.73 m(2) after 24 months. Allopurinol treatment slowed down renal disease progression independently of age, gender, diabetes, C-reactive protein, albuminuria, and renin-angiotensin system blockers use. After a mean follow-up time of 23.4 +/- 7.8 months, 22 patients suffered a cardiovascular event. Diabetes mellitus, previous coronary heart disease, and C-reactive protein levels increased cardiovascular risk. Allopurinol treatment reduces risk of cardiovascular events in 71% compared with standard therapy.

Conclusions: Allopurinol decreases C-reactive protein and slows down the progression of renal disease in patients with chronic kidney disease. In addition, allopurinol reduces cardiovascular and hospitalization risk in these subjects.

Figure 1.

Patient flow chart.

Figure 2.

Change in UA levels and change in eGFR at the end of study. Values are expressed as mean ± SEM.

Figure 3.

Effect of allopurinol treatment in cardiovascular events. Log rank: 4.25; P = 0.039.