Saturday, June 26, 2010: Free Communications

Introduction and Aims: Oxidative stress (OS) causing endothelial dysfunction (ED) is thought to be a major reason why renal patients suffer more cardiovascular (CV) events than would be expected from their conventional risk factors such as BP. One way to reduce OS is to prevent its formation by using allopurinol to block xanthine oxidase (XO)-induced OS. In this study, we examined if allopurinol really does improve ED in renal patients. Methods: A randomised, double-blind, placebo-controlled, parallel study was conducted in 67 patients with chronic kidney disease (CKD) stage 3. Subjects received 100mg Allopurinol once a day for the initial 2 weeks, and then increased to 300mg Allopurinol once a day for the remaining 9 months, or placebo. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery, while central arterial stiffness was assessed by pulse wave analysis (PWA) and pulse wave velocity (PWV). Results: 50 patients completed the study (24 active, 26 placebo). Mean age, estimated glomerular filtration rate (eGFR) and clinic BP were 72±8 years, 45±11 ml/min/1.73m2, and 144/74 (± 18/8) mmHg respectively. Allopurinol significantly improved brachial artery FMD [ FMD was +1.3% (± 3.1%) in the active group and -0.8% (±2.9%) in the placebo group (p=0.020)]. There was no difference in response to glyceryl trinitrate between both treatment arms. The central augmentation index (AIx) improved significantly on allopurinol [ AIx was -4.7% (±9.9%) in the active group and +1.7% (±7.0%) in the placebo group (P=0.011)]. PWV also significantly improved in patients on allopurinol [ PWV was -0.3 m/sec (±1.1) in the active group and +0.4 m/sec (±1.5) in the placebo group (P=0.048)]. Renal function remained stable in both groups throughout the whole study period. Conclusions: This is the first study to demonstrate that in patients with mild to moderate CKD, treatment with allopurinol significantly improved endothelial function when assessed using 3 contemporary but different modalities. As ED is an important surrogate marker that predicts future CV events, allopurinol could potentially reduce the adverse prognosis associated with renal dysfunction.