Reduction of uric acid levels with allopurinol treatment improves endothelial function in patients with chronic kidney disease

Abstract

Background: Endothelial dysfunction (ED) is a key event in the development of atherosclerotic cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Association of hyperuricemia with CVD has been previously reported in the non-uremic population. In this prospective study, we aimed to evaluate the effects of treatment of hyperuricemia with allopurinol on ED and changes in the serum reactive oxygen species in patients with CKD. Methods: In this study, 19 (13 male) hyperuricemic (UA > 7 mg/dl) nondiabetic CKD patients without any comorbidity, aged < 60 years with creatinine clearance (CrCl) between 20 and 60 ml/min were evaluated. Endothelial functions were assessed by ischemia-induced forearm vasodilatation method (EDD). Oxidative stress was evaluated by measuring the serum oxidized LDL (ox-LDL), advanced oxidation protein products (AOPP) and nitrotyrosine (NT) levels. After measuring all these tests at baseline, allopurinol therapy was commenced for 8 weeks. After 8 weeks of allopurinol treatment, all measurements were repeated. Then, allopurinol treatment was ceased and same measurements were also repeated 8 weeks after ceasing of the treatment. Results: Serum creatinine, total cholesterol, albumin, hs-CRP, CrCl and proteinuria levels of the patients were similar among three study periods. After allopurinol therapy, the mean serum UA and NT levels significantly reduced as compared to baseline. At the 8th week after cessation of allopurinol treatment, serum UA levels were significantly increased. After allopurinol therapy, EDD value increased from 5.42 +/- 8.3% at baseline to 11.37 +/- 9% (p < 0.001). At the 8th week after ceasing allopurinol treatment, EDD returned to baseline values (5.96 +/- 8%, p < 0.001). Conclusion: Treatment of hyperuricemia with allopurinol improve ED in patients with CKD. However, mechanism responsible for this beneficial effect seems to be apart from antioxidant effects of allopurinol.