Thrombotic events and markers of oxidation and inflammation in hemodialysis

The goal of this study was to determine whether antioxidant therapy with vitamin E would alter the rate of vascular access complications or other macrovascular complications in hemodialysis (HD) patients. A secondary goal of the study was to explore the relationship between baseline pretreatment markers of oxidative stress (the advanced glycation end product pentosidine and basal levels of vitamin Ealpha and gamma) and the subsequent development of access failure. Thirty-five stable patients treated by HD were recruited for the study. Patients were provided with vitamin E (800 IU) or placebo capsules to be taken daily. Clinical variables, vascular access function (flow meter access flow measurements), and circulating blood markers were obtained initially and every 3 months throughout the study. Vitamin Ealpha levels rose in treated patients from 12.7 +/- 4.4 to 25.1 +/- 15.1 microg/mL at 3 months and 28.6 +/- 14.8 microg/mL at 6 months. Vitamin Egamma levels fell in treated patients from 3.9 +/- 1.7 to 2.3 +/- 1.5 microg/mL at 3 months and 1.7 microg/mL at 6 months. Patients who subsequently developed repeated thrombotic vascular access events were characterized by higher baseline pentosidine content of circulating proteins. Patients who developed a myocardial infarction had higher pentosidine, lower vitamin Ealpha, and much lower vitamin Egamma than patients who did not develop thrombotic events. These findings lead to the speculation that the anti-inflammatory effects of vitamin Egamma may play a more important role in thrombotic vascular events than the antioxidant effects of vitamin Ealpha. Additional studies of these interactions are in progress.