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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL036015-04
Application #
3350499
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1987-08-01
Project End
1990-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203
Himmelfarb, Jonathan; Evanson, James; Hakim, Raymond M et al. (2002) Urea volume of distribution exceeds total body water in patients with acute renal failure. Kidney Int 61:317-23
Himmelfarb, J; McMonagle, E; Holbrook, D et al. (1999) Increased susceptibility to erythrocyte C5b-9 deposition and complement-mediated lysis in chronic renal failure. Kidney Int 55:659-66
Evanson, J A; Ikizler, T A; Wingard, R et al. (1999) Measurement of the delivery of dialysis in acute renal failure. Kidney Int 55:1501-8
Neyra, N R; Ikizler, T A; May, R E et al. (1998) Change in access blood flow over time predicts vascular access thrombosis. Kidney Int 54:1714-9
Hakim, R; Himmelfarb, J (1998) Hemodialysis access failure: a call to action. Kidney Int 54:1029-40
Himmelfarb, J; Tolkoff Rubin, N; Chandran, P et al. (1998) A multicenter comparison of dialysis membranes in the treatment of acute renal failure requiring dialysis. J Am Soc Nephrol 9:257-66
May, R E; Himmelfarb, J; Yenicesu, M et al. (1997) Predictive measures of vascular access thrombosis: a prospective study. Kidney Int 52:1656-62
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
Hakim, R M; Held, P J; Stannard, D C et al. (1996) Effect of the dialysis membrane on mortality of chronic hemodialysis patients. Kidney Int 50:566-70
Hakim, R M; Wingard, R L; Husni, L et al. (1996) The effect of membrane biocompatibility on plasma beta 2-microglobulin levels in chronic hemodialysis patients. J Am Soc Nephrol 7:472-8

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