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 membranes with different biocompatibilities, we will study these interaction 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 study the effects of chronic complement activation and release of the Membrane Attack Complex (MAC) on red blood cell (RBC) survival in hemodialysis patients. (2) To study the effects of chronic complement activation and release of MAC on platelet function in hemodialysis patients. (3) To study the effects of chronic complement and granulocyte activation with release of ROS on lipid peroxidation. (4) To continue or study of the effects of the dialysis membrane on the recovery of patients with acute renal failure. (5) To study the reversibility of these phenomena in the same patient population with biocompatible, non-complement activating dialysis membranes.
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