Protein-energy malnutrition, a well-established major risk factor for morbidity and mortality, is found in 40% of patients with end-stage-renal disease. Investigators have shown that malnutrition develops before the initiation of dialysis in a large portion of patients, particularly when residual renal function declines to less than 25% of normal. Despite advances in renal replacement therapy, no significant improvement has been observed in the nutritional status of ESRD patients. To overcome this problem, three promising interventions have been highlighted. These include: 1) timely initiation of dialysis; 2) increased dose of hemodialysis; and 3) treatment with anabolic agents. The applicant proposed to investigate these three approaches to improve nutritional status of patients with chronic renal failure (CRF). The applicant will test a hypothesis that using """"""""early"""""""" versus """"""""conventional"""""""" criteria for initiation of dialysis preserves nutrient homeostasis and subsequent morbidity. Patients with moderate CRF will be randomized to dialysis using either early or conventional criteria for initiation to evaluate how nutritional status, hospitalization rate and death are altered over a two-year period. The applicant will also test the hypothesis that a higher than """"""""adequate"""""""" dose of dialysis improves nutritional status in patients with CRF using patients who will be randomized to receive two doses of dialysis over a two-year period. Furthermore, the effect of the administration of recombinant-human- growth hormone on nutritional status will be evaluated in patients with ESRD. These three studies will establish the link between malnutrition and renal failure, and provide the basis for intervention to improve nutritional status.
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