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30万的患者正在接受慢性透析治疗，预计到2010年这一人群将迅速增加到60万以上，到2030年将超过200万。透析患者的预期寿命仅为普通人群的1/3至1/6，心血管疾病约占死亡率的50%。目前，没有任何治疗方法被证明可以降低透析人群心血管发病率和死亡率的风险。在Framingham研究中，传统的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和尿毒症的发病机制，最近已确定为氧化应激增加状态。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治疗，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结合起来。辅酶Q10在治疗充血性心力衰竭和改善II型糖尿病患者内皮功能和保留肾功能方面具有显著的临床益处。血浆中辅酶Q10的浓度似乎反映了净总体代谢需求，我们的初步数据表明，血液透析患者血浆中辅酶Q10的水平较低，这表明辅酶Q10可能是这些患者理想的抗氧化剂。本应用的中心假设是辅酶Q10作为靶向抗氧化治疗将是安全且耐受性良好的，并将改善血液透析患者过度的氧化应激负担。这反过来将导致心血管风险替代标志物的改善。我们建议通过以下具体目的来检验这一假设：A.1。探讨不同剂量辅酶Q10膳食补充剂对血液透析患者的安全性和耐受性。由信用证。研究膳食补充剂辅酶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。

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.