Chronic uremia in humans, due to end-stage renal disease, is associated with a significant morbidity and mortality. A number of endocrine and metabolic disturbances have been associated with this syndrome. The major objectives of the proposed investigations are to quantify the effects of altered endocrine regulations in chronic uremia on carbohydrate and fuel metabolism. In humans, safe stable isotopic tracers and mass spectrometric methods in combination with indirect respiratory calorimetry will be employed to quantify the contribution of carbohydrate, protein and fat to total energy metabolism. The reversibility of these alterations by idealized dietary and hemodialysis treatment will also be examined. In the long run, it is hoped that these studies will help in better understanding of the altered physiology in uremia and may result in improved clinical care.