Exercise to Prevent Muscle Mass and Functional Loss in Elderly Dialysis Patients
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Study type: Interventional

Summary: 
      The majority of individuals with advanced ESRD have reduced exercise capacity in part due to
      decreased muscle mass. This leads to a reduced ability to perform daily activities, a greater
      incidence of falls, and a reduced quality of life. The mechanisms responsible for the loss of
      muscle mass in ESRD are not understood very well. This study is designed to determine the
      effectiveness of an exercise program on improving muscle mass, exercise capacity and quality
      of life in persons with ESRD. In addition, the study will attempt to better understand why
      muscle loss occurs in people with ESRD, the influence exercise has on these mechanisms, and
      whether the response to exercise can be enhanced with nutrient supplementation.
    

Detailed description: 
      Elderly patients comprising half the end-stage renal disease (ESRD) population, are
      especially 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 exercise (EX), including endurance, resistance or combined, can counteract the
      loss of muscle mass and function. However most studies have not specifically targeted the
      elderly, involved small numbers or lacked controls and the impact on long-term outcome is
      unknown. Nevertheless, despite substantial evidence indicating that EX is beneficial and low
      cost, EX is not part of the routine care of MHD patients. In contrast EX is regarded as
      standard of care for the wasted elderly and also cardiac patients. 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 (PS) and also directly
      activate the mTOR signaling pathway stimulating PS. In normal subjects if AA are ingested at
      the time of resistance EX, anabolic signaling and PS is enhanced and this leads to increases
      in muscle mass. Whether the EX and AA stimulated signaling response is intact in elderly MHD
      patients is unknown and there is little information about the cellular processes invoked.
      Taking this all together, the investigators plan to test the hypothesis that a home-based EX
      program, effective in cardiac patients, will improve cardiopulmonary function and muscle mass
      and function in elderly MHD patients. Also, in a pilot study the investigators will examine
      whether a protein supplement acutely enhances EX stimulated anabolic signaling. Functionally
      impaired MHD subjects aged 65-80 yrs are randomized into 2 groups of 30 each, one undergoing
      EX and the other usual care. After 3 months, half in each group receive a one-time
      protein-calorie supplement or placebo during an acute bout of EX and muscle biopsied for
      examining the signaling response. Assays at baseline and at 3 months include cardiopulmonary
      function, muscle strength and function, body composition by DEXA, thigh muscle volume and
      composition by CT, quality of life (QOL) and cognitive function, and nutritional,
      inflammatory, lipid and biochemical status and morphologic and molecular analysis of biopsied
      muscle. The investigators anticipate that home-based EX will counteract muscle wasting,
      enhance cardiopulmonary and muscle function and QOL, and reduce surrogate markers of
      long-term outcome. New insights into the mechanisms whereby EX and nutrients induce an
      anabolic response in muscle of elderly uremics will be provided and may serve as a basis for
      devising strategies to counteract loss of muscle mass and function. Finally, the
      investigators anticipate that the EX program will be "user friendly" and may thus form a part
      of the routine care of elderly and perhaps younger MHD patients. If short-term benefits are
      evident from this study in elderly MHD patients, it could form the basis for a comprehensive
      long-term outcomes study.
    

Intervention name(s): Exercise training; Usual Care
Intervention type(s): Other; Other
Intervention description(s): Subjects will participate in a center-based and home exercise training program for 3 months.; This group will serve as control subjects. They will receive only usual clinical care.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Renal failure; Exercise testing; Exercise training; Protein signaling; Skeletal muscle