Significant interactions occur at the interface between dialysis membranes and blood during every hemodialysis. Increasing evidence suggests that these interactions have an adverse effect on the morbidity and mortality of the more than 80,000 chronic hemodialysis patients in the United States; Therefore biocompatibility issues in hemodialysis have direct and substantial economic and health implications. Interactions between blood and cuprophane, the most widely used dialysis membrane results in the activation of the complement as well as the coagulation cascade and the contact phase (kallikrein) pathway; activation of neutrophils as well as platelets has also been demonstrated. The objectives of this proposal are several: 1. To investigate the functional characteristics of neutrophils (phagocytosis, metabolic activity) during and after chronic dialysis with different membranes. 2. To investigate the activation of platelets during dialysis with different dialysis membranes and its relationship to uremic bleeding. 3. To identify the interactions between activated neutrophils and platelets in whole blood. 4. To continue work on animal models to investigate the effects of different pharmacological agents and metabolic inhibitors on the acute response to blood/membrane interaction. 5. To investigate the biocompatibility of membranes in terms of their adsorption of various biologically active products. 6. To identify and investigate the activation of other pathways that may be important in the long term morbidity of dialysis patients such as Interleukin-I, and tumor necrosis factor.
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