Mortality among patients with end-stage renal disease treated by hemodialysis in the United States is high and increasing, despite recent improvements in dialysis techniques. Principal factors postulated to contribute to the high mortality include 1) inadequate prescription and delivery of dialysis, 2) advanced age, diabetes, and other risk factors for cardiovascular disease, and 3) repeated activation of proinflammatory mediators by exposure to dialysis membranes. NIDDK plans to conduct a controlled trial to determine the effect of interventions to reduce morbidity and mortality in hemodialysis patients. The proposed study is a randomized trial of the effect of three interventions, employing a 2x2x2 factorial design and an intention-to-treat analysis of mortality, morbidity and cost. 1) Prescription of more intensive dialysis and protein nutrition, defined and monitored by parameters from urea kinetic modeling. Experimental therapy includes goals for KT/V of 1.4-1.6 and for PCR(n) of 1.2-1.5 g/kg/day; while standard therapy includes goals for KT/V of 1.0-1.2 and for PCR(n) of 0.8-1.2 g/kg/day. 2) Prescription of a more intensive program of reduction of multiple cardiovascular risk factors. Experimental therapy includes angiotensin converting enzyme inhibitors (ACEI) and lower than usual prescribed goals for blood pressure, serum triglycerides and cholesterol. Standard therapy includes omission of ACEI and usual goals for blood pressure, serum triglycerides and cholesterol. 3) Prescription of more biocompatible dialysis membranes, defined as membranes which do not activate complement and induce leukoagglutination. Experimental therapy includes synthetic high flux membranes. Standard therapy includes conventional or high efficiency cellulose membranes. This study will be conducted at two dialysis units with an out-patient population of 185 patients. Based on chart review. approximately 70 patients would be eligible for entry into the proposed study, which is adequate for participation in the pilot study.