Nutritional Formulation to Target Muscle Loss in CKD Patients

描述（由申请人提供）：低白蛋白血症和肌肉萎缩是晚期慢性肾脏疾病（CKD）患者死亡率和发病率的重要预测因素。肌肉的持续损失是由于基底肌蛋白代谢的改变或血液透析（HD）引起的变化。慢性肾病患者肌肉蛋白合成减少。我们已经反复证明了必需氨基酸（EAA）配方的合成代谢能力，并开发了一种旨在维持老年人肌肉质量和功能的补充剂。BeneVia(R)是受知识产权保护的产品，与现有产品相比，它有几个优势，即，它是以果汁为基础的，以小体积（不到7盎司）提供基本成分，低卡路里，包装方便。然而，进一步完善该产品是必要的，以满足CKD患者的特殊需求。BeneVia(R) Renal将作为一种营养补充剂上市，旨在维持肌肉质量和功能，并最大限度地减少HD反复发作的分解代谢影响。相应的;成分旨在改善细胞因子的产生和血液酸度。在这个i期申请中，总体目标将是确定BeneVia(R) Renal配方是否比常用配方更能刺激晚期CKD患者的肌肉蛋白质合成。我们假设单剂量（6oz或177ml） BeneVia(R) Renal可以显著刺激CKD患者的肌肉蛋白合成。此外，我们假设单剂量的BeneVia(R) Renal会比单剂量（8oz或237ml）为透析患者设计的流行营养疗法（Nepro(R)）更大程度地刺激肌肉蛋白质合成。两组12名患者将被随机分配接受BeneVia(R) Renal或Nepro(R)治疗2周，然后进行代谢研究，利用稳定同位素方法测定肌肉蛋白质合成。一种旨在恢复最佳蛋白质代谢的营养配方将抵消CKD后期发生的代谢改变，并改善肌肉蛋白质的损失和功能下降。公共卫生相关性：本建议描述了一种旨在改善晚期CKD分解代谢的营养补充剂。如果成功，结果是一种经济的营养产品，可以用来预防肾功能下降和肾脏疾病的发病率。这不仅会提高CKD患者的生活质量，而且对整体医疗保健成本有重大影响。

DESCRIPTION (provided by applicant): Hypoalbuminemia and muscle wasting are important predictors of mortality and morbidity in patients with latter stage chronic kidney disease (CKD). The persistent loss of muscle results from alterations in basal muscle protein metabolism or changes precipitated by hemodialysis (HD). A reduced synthesis of muscle proteins was noted in patients with CKD. We have repeatedly demonstrated the anabolic capacity of a formulation of essential amino acids (EAA) and have developed a supplement designed to maintain muscle mass and function in the elderly. BeneVia(R) is protected under intellectual property and has several advantages over existing products, namely, it is juice based, provides essential ingredients in a small volume (less than 7 oz), is low calorie, and is conveniently packaged. However, further refinement of this product is necessary to address the specific needs of CKD patients. BeneVia(R) Renal will be marketed as a nutritional supplement designed to maintain muscle mass and function and to minimize the catabolic effects of repeated bouts of HD. Accordingly; ingredients are targeted to ameliorate cytokine production and blood acidity. In this Phase 1 application, the general goal will be to determine if the BeneVia(R) Renal formulation stimulates muscle protein synthesis in advanced stage CKD patients to a greater extent than a commonly used formula. We hypothesize that a single dose (6oz or 177ml) of BeneVia(R) Renal will significantly stimulate muscle protein synthesis in CKD patients. Further, we hypothesize that a single dose of BeneVia(R) Renal will stimulate muscle protein synthesis to a greater extent than a single dose (8oz or 237ml) of a popular nutritional therapy designed for dialysis patients (Nepro(R)). Two groups of 12 patients will be randomly assigned to receive either BeneVia(R) Renal or Nepro(R) for 2 weeks prior to a metabolic study utilizing stable isotope methodology to determine muscle protein synthesis. A nutritional formula designed to restore optimal protein metabolism will offset the metabolic alterations that occur during the latter stages of CKD and ameliorate the loss of muscle protein and functional decline. PUBLIC HEALTH RELEVANCE: This proposal describes a nutritional supplement designed to ameliorate the catabolism of advanced CKD. If successful, the result is an economical nutritional product that can be utilized to prevent declines in function and morbidity with renal disease. This will not only improve quality of life in CKD patients, but have a significant impact on overall health care costs.