Several pathways of the inflammatory response are activated at the interface between blood and cuprophane dialysis membrane, the most widely used dialysis membranes. Increasing evidence suggests that these interactions have an adverse effect on the morbidity and mortality of the more than 100,000 chronic hemodialysis patients in the United States and on the recovery of renal function in acute renal failure; therefore, biocompatibility issues in hemodialysis have direct and substantial economic and health implications. Interactions between blood and cuprophane membrane results in the activation of the complement, coagulation and the contact phase pathway, as well as cellular elements such as neutrophils, monocytes and lymphocytes. The broad objective of this proposal is to study these interactions, their biochemical and clinical consequences as well as their modification with different dialysis membranes, with the long term objective of reducing the morbidity and mortality of the hemodialysis patient. Using two membranes with different biocompatibilities, we will study these interactions in prospective, cross-over studies of chronic hemodialysis patients as well as randomized, prospective studies of patients initiating hemodialysis.
Specific aims of this proposal are: 1. to investigate the effects of recurrent activation of neutrophils on their phagocytic ability, the frequency of infection as well as on the recovery from acute renal failure. 2. to investigate the consequences of the recurrent interactions between activated neutrophils and endothelial cells on pulmonary function and on Beta2 amyloid disease in dialysis patients. 3. to investigate the consequences of recurrent monocyte and lymphocyte activation on selected cell-mediated immune responses.
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