Safety, Tolerability and Efficacy of Coenzyme Q10 in Hemodialysis Patients

描述（由申请人提供）：目前在美国有超过30万名患者接受长期透析治疗，预计到2010年，这一人群将迅速增加到超过60万名患者，到2030年将超过200万名患者。透析患者的预期寿命仅为一般人群的1/3至1/6，心血管疾病约占死亡率的50%。目前，尚无经证实可降低透析人群心血管发病率和死亡率风险的疗法。Frachial研究中举例说明的传统心血管危险因素对透析患者的预后价值有限，这表明受尿毒症代谢环境影响的“非传统”危险因素可能特别重要。氧化应激增加有助于动脉粥样硬化的发病机制，尿毒症最近被确定为氧化应激状态增加。辅酶Q10是一种容易获得的膳食补充剂，经常用作替代和补充疗法，是一种有效的亲脂性抗氧化剂，可将线粒体中的电子传递与氧化磷酸化偶联。辅酶Q10给药与治疗充血性心力衰竭的显著临床获益相关，并改善II型糖尿病患者的内皮功能和保留的肾功能。辅酶Q10的血浆浓度似乎反映了净总体代谢需求，我们的初步数据表明，血液透析患者的血浆辅酶Q10水平降低，表明辅酶Q10可能是这些患者理想的抗氧化剂。本申请的中心假设是给予辅酶Q10作为靶向抗氧化剂治疗将是安全的和良好耐受的，并且将改善血液透析患者中过度的氧化应激负荷。这反过来将导致心血管风险的替代标志物的改善。我们建议通过以下具体目标来检验这一假设：确定不同剂量膳食补充剂辅酶Q10在血液透析患者中的安全性和耐受性。A.2.检测膳食补充剂辅酶Q10对血液透析患者氧化应激、全身炎症和内皮功能生物标志物的影响。 公共卫生相关性：接受长期透析治疗的患者因心血管疾病而死亡率很高。该项目旨在测试辅酶Q10（一种现成的膳食补充剂）的给药是否会对透析患者产生临床益处。这项研究还旨在测试辅酶Q10用于透析是否安全且耐受良好。

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.