: Nutritional status is an important predictor of clinical outcome in chronic hemodialysis (CHD) patients, as uremic malnutrition is strongly associated with increased risk of death and hospitalization events. Decreased muscle mass is the most significant predictor of morbidity and mortality in these patients. Several factors predispose CHD patients to increased catabolism and loss of lean body mass. Chronic hemodialysis patients suffer from profound anorexia and have decreased dietary protein intake. Further, these patients live a sedentary life-style and their physical activity level is low. In combination, these factors predispose CHD patients to a catabolic state leading to loss of muscle mass. These observations led us to hypothesize that supplementing dietary protein intake along with an anabolic intervention such as exercise will collectively improve uremic malnutrition. The broad goal of this proposal is to identify the mechanism(s) by which CHD patients lose muscle mass and test certain interventions that will either prevent whole-body and muscle protein breakdown or enhance muscle growth. We will perform stable isotope tracer techniques to assess protein and energy homeostasis and compliment these studies proinflammatory cytokine profiles in the muscle tissue. This proposal will test the hypotheses that A) Acute exercise protocol combined with adequate nutritional supplementation improves skeletal muscle protein accretion during a single hemodialysis session; B) If performed long-term at increasing intensity, this protocol (exercise combined with adequate nutritional supplementation) will result in net muscle growth in CHD patients.
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