Hemodialysis is a life-sustaining procedure for more than 100,000 patients in the United States. However, morbidity and mortality due to infection and cardiovascular disease remain high in this patient population. The objective of this proposal is to examine the effects of different hemodialysis membranes on host defenses against infection and risks for cardiovascular disease, by examining the effects of different dialysis membranes on phagocytic cell function. An improved understanding of changes in granulocyte and monocyte function with different dialysis membranes will lead to decreased patient morbidity and mortality, with substantial economic and health implications for this patient population. During every hemodialysis procedure, significant interactions occur at the interface between dialysis membranes and blood components. In particular, cuprophane, the most widely used dialysis membrane in the United States, causes complement activation as well as granulocyte and monocyte activation. Other pathways such as contact activation and direct contact between cells and dialysis membranes may also affect granulocyte and monocyte function during hemodialysis. The objective of this proposal are: 1) to perform a prospective controlled trial examining the effects of different hemodialysis membranes on multiple aspects of granulocyte and monocyte function, including changes in phagocytosis, reactive oxygen species production, binding to and transmigration of endothelium and proteolytic enzyme release; 2) to establish the relationship in a prospective controlled trial between changes in granulocyte and monocyte oxidative metabolism during hemodialysis and the oxidative modification of lipoprotein fractions; and 3) to determine the relative roles of complement activation, contact activation and direct membrane stimulation in causing granulocyte and monocyte functional changes during hemodialysis with different membranes.
| Becker, B N; Himmelfarb, J; Henrich, W L et al. (1997) Reassessing the cardiac risk profile in chronic hemodialysis patients: a hypothesis on the role of oxidant stress and other non-traditional cardiac risk factors. J Am Soc Nephrol 8:475-86 |
| Himmelfarb, J; McMonagle, E; Holbrook, D et al. (1995) Soluble complement receptor 1 inhibits both complement and granulocyte activation during ex vivo hemodialysis. J Lab Clin Med 126:392-400 |
