The federally-funded End Stage Renal Disease program was initiated in 1972 with the goal of extending the lives of individuals with kidney disease and allowing them to return to the work force. Though dialysis has prolonged the lives of patients with ESRD, it has not produced the expected degree of occupational and physical rehabilitation. A recent study showed that more than one third of hemodialysis patients had a Karnofsky score below 70, meaning that they were unable to perform the normal activities of daily living without assistance. Investigation into the causes of this striking debility has been limited, but muscle atrophy and concomitant weakness probably contribute. Reduced lean body mass (LBM) and muscle weakness have been demonstrated in this population. Since muscle strength correlates with performance measures such as gait speed in elderly subjects, the reduction in LBM in dialysis patients may affect functional status, and treatments designed to increase muscle size and strength could be of benefit to such individuals. Both anabolic steroid treatment and resistance exercise training (RE) increase strength and muscle mass in healthy subjects. RE also resulted in improved functional status in frail elderly subjects. While there have been no reports of the effects of RE in patients on dialysis, we recently showed that nandrolone decanoate (ND), a 19-nortestosterone derivative, increased LBM and improved walking and stair-climbing time in patients on dialysis. Furthermore, ND was safe in this population and resulted in only occasional mild side effects. In the current application, we propose to perform two studies concurrently. In one, to elucidate the mechanisms of the muscle defects of dialysis patients, healthy control subjects and patients on dialysis will undergo measurement of physical activity levels, and of muscle size, strength, and oxidative capacity. In the second, we will determine whether RE and/or anabolic steroids can increase muscle size and improve muscle strength and physical performance in patients on hemodialysis. In a 12-week study, 80 hemodialysis patients will be randomly assigned to one of 4 groups as follows: ND, weekly ND injections; EX, resistance exercise training plus placebo injections; ND-EX, ND injections plus RE; and PL, placebo injections only.
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