This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Maintenance hemodialysis (MHD) patients often complain of malaise, weakness and exercise intolerance and display a myopathy. Endurance exercise training (ET) and erythropoietin improve their endurance capacity, but not to normal. Our pilot study in MHD patients indicates that endurance exercise training (ET) decreases gene expression for myostatin, a protein that suppresses skeletal muscle hypertrophy, and increases mRNA for insulin-like growth factor-I (IGF-I) and the IGF-receptor (IGF-R). This project will examine the primary hypothesis that in MHD patients strength training (ST), ET or a combination of ST and ET, as compared to no training (NT), leads, in skeletal muscle, to decreased mRNA for myostatin. The main secondary hypothesis are that, in skeletal muscle, ST, ET and a combination of ET and St, as compared to NT, increase mRNA for IGF-I, IGF-R, and myosin heavy chains and the IGF-I, IGF-R, and myosin heavy chain proteins and decrease myostatin. It is further hypothesized that ET, ST and a combination of ET and ST will alter nRNA for IGF binding proteins, cause skeletal muscle hypertrophy (as determined by cross-sectional muscle fiber area, DEXA, anthropometry), and improve skeletal muscle morphology (as indicated by a more normal proportion of type IIa/IIx fibers and mitochondrial structure) and biochemistry (e.g., increased succinate dehydrogenase activity); also that endurance and strength capacity and other clinical variables will improve. It is hypothesized that ST will have a greater effect on muscle strength and processes associated with skeletal muscle hypertrophy, whereas ET will promote greater endurance exercise capacity and muscle aerobic enzyme activity (e.g., succinate dehydrogenase activity). The combination of ET and ST, by combining the elements of both exercise training regimens, will improve both types of processes. Also, a combination of ET and ST and, to a lesser degree, ST and ET employed separately, will make most of these measures more similar to those of healthy, non-exercise trained adults. Clinically stable MHD patients will enter a baseline phase where initial measurements are obtained and relevant clinical variables are standardized. Patients will then be randomized to receive ST, ET, ET and ST or NT (20 patients per group) for 6 months. ST, ET or the combination of ET and ST will be performed thrice-weekly for up to 40 minutes, before or during the first 90 minutes of MHD. Outcome measures will then be repeated; measures from the four treatment groups will be compared to each other and to healthy adults.
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