Exercise to Prevent Muscle Mass and Functional Loss in Elderly Dialysis Patients

通过运动预防老年透析患者的肌肉质量和功能丧失

• 批准号: 8586711
• 负责人: Jonathan N. Myers
• 金额: --
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8586711
• 关键词: Acidosis; Acute; Aerobic; Aging; Amino Acids; Androgen Receptor; Anemia due to Chronic Disorder; Biochemical; Biopsy; Body Composition; Calories; Cardiac; Cardiopulmonary; Cardiovascular Diseases; Cell physiology; Chronic Kidney Failure; Dialysis patients; Elderly; End stage renal failure; Exercise; Exercise Tolerance; Hemodialysis; Home environment; Hormones; Individual; Inflammatory; Insulin; Insulin-Like Growth Factor I; Intake; Lead; Leucine; Life Style; Lipids; Maintenance; Messenger RNA; Modality; Molecular; Morbidity - disease rate; Muscle; Muscle function; Nutrient; Nutritional; Outcome; Outcome Study; Patients; Pilot Projects; Placebos; Population; Process; Protein Biosynthesis; Proteins; Proteolysis; Quality of life; Randomized; Regimen; Resistance; Signal Pathway; Signal Transduction; Signaling Protein; Skeletal Muscle; Source; Supervision; Supplementation; Surrogate Markers; Testing; Thigh structure; Time; Training; aged; base; cardiovascular risk factor; cognitive function; cost; cost effective; disability; frailty; functional loss; human FRAP1 protein; improved; insight; mTOR Signaling Pathway; middle age; mortality; muscle form; muscle strength; myostatin; novel strategies; older patient; prevent; programs; public health relevance; response; routine care; satellite cell; sedentary; standard of care; treatment as usual; user-friendly; wasting

DESCRIPTION (provided by applicant): Elderly patients comprise half of the end-stage renal disease (ESRD) population and are particularly vulnerable to loss of muscle mass, strength and function - changes that lead to frailty and increased morbidity and mortality. Many factors contribute to the decline in muscle mass and function in the elderly uremic, and apart from aging and co-morbid conditions, wasting is worsened by inactivity. Studies in maintenance hemodialysis (MHD) patients have shown that regular exercise, including aerobic, resistance or combined modalities, can counteract the loss of muscle mass and function in these patients. However, most studies have not specifically targeted the elderly, have involved small numbers or lacked controls, and the impact on long-term outcomes is unknown. Nevertheless, despite substantial evidence indicating that exercise is beneficial and cost-effective, it is not part of the routine care of MHD patients. In contrast, among patients with cardiovascular disease and other conditions associated with muscle wasting, regular exercise is regarded as standard of care. Some protection against uremic muscle wasting can also be afforded by an adequate protein-calorie intake. Amino acids (AA) from this source serve as substrates for protein synthesis and also directly activate the mTOR signaling pathway which further stimulates protein synthesis. In normal subjects, if AA are ingested at the time of resistance exercise, anabolic signaling and protein synthesis are enhanced and this leads to increased muscle mass. Whether the exercise and AA-stimulated signaling response is intact in elderly MHD patients is unknown, and there is little information regarding the cellular processes invoked. Taking this all together, we plan to test the hypothesis that a home-based exercise program, effective in cardiac patients, will improve cardiopulmonary function and muscle mass and function in elderly MHD patients. In addition, in a pilot study we will examine whether a protein supplement acutely enhances exercise- stimulated anabolic signaling. Functionally impaired MHD subjects aged 65-80 years will be randomized into two groups of 30 each, one undergoing exercise training and the other usual care. After 3 months, half of each group will receive a one-time protein-calorie supplement while the other half will receive placebo during an acute bout of exercise, and muscle will be biopsied for examining the signaling response. Assesments at baseline and 3 months will include cardiopulmonary function, muscle strength and function, thigh muscle volume and composition, whole body composition, quality of life (QOL), cognitive function, nutritional, inflammatory, lipid and biochemical status, and morphologic and molecular analyses of biopsied muscle. We anticipate that home-based exercise will counteract muscle wasting, enhance cardiopulmonary and muscle function and QOL, and reduce surrogate markers of long-term outcome. New insights into mechanisms whereby exercise and nutrient supplementation induce an anabolic response in muscle of elderly MHD patients will be provided, which may serve as a basis for devising strategies to counteract loss of muscle mass and function in these individuals. Finally, we anticipate that our exercise program will be "user-friendly" and may thus form part of routine care of elderly, and perhaps younger MHD patients. If short-term benefits are evident from this study in the elderly, it could form the basis for a broader long-term outcomes study.

描述（由申请人提供）： 老年患者占末期肾脏疾病（ESRD）人群的一半，特别容易受到肌肉质量，力量和功能损失的影响 - 导致脆弱，发病率和死亡率增加的变化。许多因素导致老年尿毒症的肌肉质量和功能的下降，除了衰老和合并状况外，浪费会因不活动而恶化。维持血液透析（MHD）患者的研究表明，定期运动，包括有氧，耐药性或联合方式，可以抵消这些患者的肌肉质量和功能的丧失。但是，大多数研究并未专门针对老年人，涉及少量或缺乏对照，并且对长期结局的影响尚不清楚。然而，尽管有大量证据表明运动是有益且具有成本效益的，但它并不是MHD患者常规护理的一部分。相反，在心血管疾病的患者和与肌肉浪费有关的其他疾病中，定期运动被视为护理标准。适当的蛋白质摄入量也可以提供一些防止尿毒症浪费的保护。来自该源的氨基酸（AA）是蛋白质合成的底物，还直接激活MTOR信号通路，从而进一步刺激蛋白质合成。在正常受试者中，如果在抵抗运动时摄入AA，则可以增强合成代谢信号传导和蛋白质合成，这会导致肌肉质量增加。在老年MHD患者中，运动和AA刺激的信号反应是否完整是未知的，并且关于所调用的细胞过程的信息很少。我们计划将所有这些假设综合起来，即对心脏患者有效的家庭运动计划将改善老年MHD患者的心肺功能和肌肉质量以及功能。此外，在一项初步研究中，我们将检查蛋白质补充剂是否急性增强运动的合成代谢信号传导。在功能上受损的65-80岁的MHD受试者将被随机分为两组30组，一组接受运动训练，另一种通常的护理。 3个月后，每组的一半将获得一次性的蛋白质 - 热量补充剂，而另一半将在急性运动期间接受安慰剂，并且肌肉将被活检以检查信号反应。基线和3个月的评估将包括心肺功能，肌肉力量和功能，大腿肌肉体积和组成，全身成分，生活质量（QOL），认知功能，营养，炎症，脂质和生物化学状态，以及对生物型肌肉的形态学和形态学和分子分析。我们预计，基于家庭的运动将抵消肌肉浪费，增强心肺和肌肉功能以及QOL，并减少长期结局的替代标记。对机制的新见解，将提供运动和营养补充剂在老年MHD患者的肌肉中引起合成代谢反应，这可能是设计策略以抵消这些人肌肉质量和功能的策略的基础。最后，我们预计我们的锻炼计划将“用户友好”，因此可能会成为老年人和可能年轻的MHD患者的常规护理的一部分。如果从老年人的这项研究中可以明显看出短期益处，则可能是更广泛的长期结果研究的基础。