Biochemical mechanisms involved in blood-hemodialysis membrane interactions
- Jeffrey S Berns, MD
Jeffrey S Berns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Dialysis
- Professor of Medicine
- Perelman School of Medicine at the University of Pennsylvania
The contact of blood with dialysis membranes elicits an organized inflammatory response that involves the activation of the body's defense against "non-self." A biocompatible membrane (BCM) has traditionally been defined as "one that elicits the least amount of inflammatory response in patients exposed to it" . It has been suggested, however, that "adsorption" (ie, binding) of low molecular weight proteins or peptides on certain types of dialysis membranes represents an additional mechanism of clearance during dialysis and may also be important in defining the biocompatibility of the membrane .
This topic will review the pathways activated during the interaction of blood with biomaterials and the contribution of adsorption to modifying the inflammatory response resulting from this interaction. The known interactions between blood and the new hemodialysis membranes will be emphasized, with only limited attention to the effect of reuse. Because hemodialysis is a repetitive procedure, minor reactions induced by the membrane at each treatment can eventually lead to adverse long-term clinical sequelae. The acute and chronic clinical sequelae of blood-membrane interactions are discussed separately. (See "Reactions to the hemodialysis membrane" and "Clinical consequences of hemodialysis membrane biocompatibility".)
In the broadest sense, all aspects of the dialysis treatment affect biocompatibility. These include dialysate composition and temperature, the permeability/porosity of the dialysis membrane, the type of clearance (diffuse or convective), the initial sterilant (eg, ethylene oxide), reuse procedure and sterilant (formaldehyde, hypochlorite, peroxyacetic acid/hydrogen peroxide), and residual materials from the manufacturing process. However, it is the biocompatibility of the membrane itself which is most important and which has been most closely studied.
COMPOSITION OF DIALYSIS MEMBRANES
Dialysis membranes can be classified into multiple groups :
- Hakim RM. Clinical implications of hemodialysis membrane biocompatibility. Kidney Int 1993; 44:484.
- Pascual M, Tolkoff-Rubin N, Schifferli JA. Is adsorption an important characteristic of dialysis membranes? Kidney Int 1996; 49:309.
- Bouré T, Vanholder R. Which dialyser membrane to choose? Nephrol Dial Transplant 2004; 19:293.
- United States Renal Data System. USRDS 1995 Annual Data Report. US Department of Health and Human Services. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, August 1995.
- United States Renal Data System. USRDS 2003 Annual Data Report. US Department of Health and Human Services. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Am J Kidney Dis 2004; 41 (Suppl 2):S187.
- Hakim RM. Complement activation by biomaterials. Cardiovasc Pathol 1993; 2:187S.
- Chenoweth DE. Complement activation in extracorporeal circuits. Ann N Y Acad Sci 1987; 516:306.
- Meri S, Pangburn MK. Discrimination between activators and nonactivators of the alternative pathway of complement: regulation via a sialic acid/polyanion binding site on factor H. Proc Natl Acad Sci U S A 1990; 87:3982.
- Kuwahara T, Markert M, Wauters JP. Biocompatibility aspects of dialyzer reprocessing: a comparison of 3 re-use methods and 3 membranes. Clin Nephrol 1989; 32:139.
- Pascual M, Steiger G, Estreicher J, et al. Metabolism of complement factor D in renal failure. Kidney Int 1988; 34:529.
- Pascual M, Catana E, White T, et al. Inhibition of complement alternative pathway in mice with Fab antibody to recombinant adipsin/factor D. Eur J Immunol 1993; 23:1389.
- Pascual M, Schifferli JA. Adsorption of complement factor D by polyacrylonitrile dialysis membranes. Kidney Int 1993; 43:903.
- Pascual M, Schifferli JA, Pannatier JG, Wauters JP. Removal of complement factor D by adsorption on polymethylmethacrylate dialysis membranes. Nephrol Dial Transplant 1993; 8:1305.
- Deppisch R, Schmitt V, Bommer J, et al. Fluid phase generation of terminal complement complex as a novel index of bioincompatibility. Kidney Int 1990; 37:696.
- Deppisch R, Ritz E, Hänsch GM, et al. Bioincompatibility--perspectives in 1993. Kidney Int Suppl 1994; 44:S77.
- Thomaneck U, Vienken J, Waldschläger U, et al. Detection of charges and their distribution on dialysis membranes with cationic/anionic dyes using confocal laser scanning microscopy. Int J Artif Organs 1991; 14:686.
- Schulman G, Hakim R, Arias R, et al. Bradykinin generation by dialysis membranes: possible role in anaphylactic reaction. J Am Soc Nephrol 1993; 3:1563.
- Krieter DH, Grude M, Lemke HD, et al. Anaphylactoid reactions during hemodialysis in sheep are ACE inhibitor dose-dependent and mediated by bradykinin. Kidney Int 1998; 53:1026.
- Wu CC, Chen JS, Wu WM, et al. Myeloperoxidase serves as a marker of oxidative stress during single haemodialysis session using two different biocompatible dialysis membranes. Nephrol Dial Transplant 2005; 20:1134.
- Arnaout MA, Hakim RM, Todd RF 3rd, et al. Increased expression of an adhesion-promoting surface glycoprotein in the granulocytopenia of hemodialysis. N Engl J Med 1985; 312:457.
- Strasser T, Schiffl H. Generation of leukotriene B4 by hemodialyzer membranes: a novel index of biocompatibility. Klin Wochenschr 1991; 69:808.
- Dinarello CA. Cytokines: agents provocateurs in hemodialysis? Kidney Int 1992; 41:683.
- Cheung AK. Biocompatibility of hemodialysis membranes. J Am Soc Nephrol 1990; 1:150.
- Schindler R, Linnenweber S, Schulze M, et al. Gene expression of interleukin-1 beta during hemodialysis. Kidney Int 1993; 43:712.
- Canivet E, Lavaud S, Wong T, et al. Cuprophane but not synthetic membrane induces increases in serum tumor necrosis factor-alpha levels during hemodialysis. Am J Kidney Dis 1994; 23:41.
- Himmelfarb J, Lazarus JM, Hakim R. Reactive oxygen species production by monocytes and polymorphonuclear leukocytes during dialysis. Am J Kidney Dis 1991; 17:271.
- Zaoui P, Green W, Hakim RM. Hemodialysis with cuprophane membrane modulates interleukin-2 receptor expression. Kidney Int 1991; 39:1020.
- Zaoui P, Hakim RM. Natural killer-cell function in hemodialysis patients: effect of the dialysis membrane. Kidney Int 1993; 43:1298.
- Bariety J, Hinglais N, Bhakdi S, et al. Immunohistochemical study of complement S protein (Vitronectin) in normal and diseased human kidneys: relationship to neoantigens of the C5b-9 terminal complex. Clin Exp Immunol 1989; 75:76.
- Zalman LS, Wood LM, Müller-Eberhard HJ. Isolation of a human erythrocyte membrane protein capable of inhibiting expression of homologous complement transmembrane channels. Proc Natl Acad Sci U S A 1986; 83:6975.
- Himmelfarb J, Lazarus J, Hakim RM. Increased expression of glycoprotein GP IIb/IIIa detected by flow cytometry on platelets during hemodialysis (abstract). Kidney Int 1987; 31:234.
- Hornych A, Rémy P, Luong N, et al. Biocompatibility of haemodialysis membranes: haemodialysis-related leukotriene B4 and C4 generation. France. Nephron 1996; 74:11.
- Kiaii M, Djurdjev O, Farah M, et al. Use of electron-beam sterilized hemodialysis membranes and risk of thrombocytopenia. JAMA 2011; 306:1679.
- COMPOSITION OF DIALYSIS MEMBRANES
- PERMEABILITY OF THE DIALYSIS MEMBRANE
- BLOOD-MEMBRANE INTERACTIONS
- Complement activation
- Importance of factor D
- Importance of terminal complement complex
- Contact pathway activation
- Coagulation pathway activation
- Activation of cellular components
- Thrombocytopenia and electron-beam sterilized membranes