Safety, Tolerability and Efficacy of Coenzyme Q10 in Hemodialysis Patients

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): There are currently more than 300,000 patients receiving chronic dialysis therapy in the United States, and it is estimated that this population will rapidly rise to over 600,000 patients by 2010 and over 2,000,000 patients by 2030. Life expectancies for dialysis patients are only 1/3 to 1/6 of those of the general population with cardiovascular disease accounting for approximately 50% of mortality. At present, there are no therapies proved to lower the risk for cardiovascular morbidity and mortality in the dialysis population. Conventional cardiovascular risk factors exemplified in the Framingham Study have limited prognostic value in dialysis patients, suggesting that "non-traditional" risk factors influenced by the uremic metabolic milieu may be particularly important. Increased oxidative stress contributes to the pathogenesis of atherosclerosis and uremia has recently been identified as an increased oxidative stress state. Coenzyme Q10, a readily available dietary supplement frequently used as an alternative and complementary therapy is a potent lipophilic antioxidant that couples electron transport to oxidative phosphorylation in the mitochondria. Coenzyme Q10 administration has been associated with significant clinical benefits in the treatment of congestive heart failure and improves endothelial function in patients with type II diabetes mellitus and preserved kidney function. Plasma concentrations of coenzyme Q10 appear to reflect net overall metabolic demand, and our preliminary data demonstrates that plasma coenzyme Q10 levels are depressed in hemodialysis patients, suggesting that coenzyme Q10 may be an ideal antioxidant for these patients. The central hypothesis of this application is that administration of coenzyme Q10 as a targeted antioxidant therapy will be safe and well tolerated, and will ameliorate the excessive oxidative stress burden in hemodialysis patients. This in turn will lead to improvements in surrogate markers for cardiovascular risk. We propose to test this hypothesis through the following Specific Aims: A.1. To determine the safety and tolerability of different doses of dietary supplement coenzyme Q10 in hemodialysis patients. A.2. To test the effect of the dietary supplement coenzyme Q10 on biomarkers of oxidative stress, systemic inflammation and endothelial function in hemodialysis patients. PUBLIC HEALTH RELEVANCE: Patients receiving chronic dialysis therapy have a high death rate due to cardiovascular disease. This project seeks to test whether administration of coenzyme Q10, a readily available dietary supplement, could result in clinical benefits for dialysis patients. This study is also designed to test whether administration of coenzyme Q10 to dialysis is safe and well-tolerated.