Recent studies indicate that maintenance hemodialysis (MHD) patients in the United States (U.S.) have a high mortality rate as compared to MHD patients reported in the EDTA Registry or in Japan who are matched according to age or for the presence or absence of diabetes mellitus. Moreover, the mortality rate among U.S. MHD patients has been increasing progressively since 1984. Several lines of evidence suggest, but do not prove, that the increased mortality is related to a reduced dialysis dose, and also that malnutrition may play a role. The present study is designed in response to an RFA for a pilot study to evaluate potential methods for reducing morbidity and mortality in MHD patients. This application proposes to test the hypothesis that increased dialysis treatment, increased protein and calorie intake and, particularly, the combination of these two treatments will reduce morbidity and mortality in adult MHD patients. The study will have a 2x2 factorial design in which clinically stable MHD patients will be randomly assigned to receive either a MHD dose that is similar to that commonly used in the U.S. or to a more intensive MHD dose. Also, patients assigned to either dialysis treatment will be prescribed a dietary protein and calorie intake similar to that ingested by many MHD patients or to a higher intake. Morbidity will be defined as the proportion of patients who remain free of evidence for medical complications, such as the frequency of hospitalizations or adverse cardiovascular or infectious events. In addition to testing the primary hypothesis concerning morbidity and mortality, the study will also examine other important secondary hypotheses concerning the effects of the four treatments on other adverse medical events, echocardiographic parameters of cardiac anatomy and function, nutritional status, serum lipids and lipoproteins, glucose tolerance, blood pressure, rehabilitation, psychosocial status, and quality of life scales. Interactions between these effects also will be analyzed. For example, a key secondary hypothesis to be tested will be that improvement in specific parameters of nutritional status will reduce morbidity or mortality.
