MUNICH, GERMANY—Allopurinol, a drug long used to treat gout, can cause regression of left ventricular hypertrophy (LVH) and improvement of endothelial dysfunction in CKD patients, a study found.
The study is the first to show that allopurinol treatment is associated with these positive effects in CKD patients. Investigators postulate that these effects may be mediated by a reduction in oxidative stress.
Prior studies have demonstrated that allopurinol can decrease oxidative stress, which promotes development of LVH and endothelial dysfunction, said lead investigator Michelle P. Kao, MD, a nephrology trainee at the University of Dundee in Dundee, UK. LVH and endothelial dysfunction are key pathophysiological processes that lead to cardiovascular events in CKD patients, according to Dr. Kao, who presented her study’s findings at the European Renal Association-European Dialysis and Transplant Association 2010 Congress.
If future studies demonstrate that allopurinol-induced regression of LVH and endothelial dysfunction translates into a reduced risk of cardiovascular events, allopurinol has the potential to provide an inexpensive way to prevent them, she said.
In a double-blind study, Dr. Kao and her colleagues randomized patients with stage 3 CKD to receive 100 mg allopurinol once daily for the initial two weeks and then 300 mg once daily for the remaining nine months, or placebo. The investigators used cardiac magnetic resonance to measure the left ventricular mass index (LVMI) and flow-mediated dilatation (FMD) of the brachial artery to assess endothelial function.
A total of 53 patients completed the study (27 in the allopurinol group and 26 in the placebo group). At nine months, the allopurinol-treated patients experienced a significant 1.42 g/m2 mean decrease in LVHI, whereas the placebo recipients had a 1.28 g/m2 increase, Dr. Kao reported. In addition, the allopurinol group had a significant 1.26% improvement in FMD compared with a 1.05% deterioration in the placebo arm.
Allopurinol was well tolerated and renal function remained stable in both groups throughout the study period.