Hemodialysis membranes: interleukins, biocompatibility, and middle molecules.
Maintenance hemodialysis patients display evidence of elevated interleukin-1 (IL-1) and tumor necrosis factor alpha release after stimulation either by contaminated dialysate, bioincompatible membrane material, or both. This release is followed by the stimulated secretion of a large number of other interleukins, particularly IL-6, the cytokine principally responsible for acute-phase protein synthesis. It has been shown that high levels of the circulating proinflammatory cytokines IL-1, tumor necrosis factor alpha, IL-6, and IL-13 are associated with mortality in hemodialysis patients. Essential functions of polymorphonuclear leukocytes--that is, phagocytosis, oxygen species production, upregulation of specific cell surface receptor proteins, or apoptosis--are disturbed in patients with end-stage renal disease. These are further altered as a result of complement activation by the hemodialysis procedure, particularly if bioincompatible dialyzers are used. Polymorphonuclear leukocyte degranulation occurring during extracorporeal circulation does not depend on complement activation but rather on intracellular calcium and the presence or absence of the degranulation inhibitory proteins angiogenin and complement factor D. Clinical signs and symptoms of end-stage renal disease patients are at least in part related to the accumulation of middle molecules such as beta(2)-microglobulin, parathyroid hormone, advanced glycation end products, advanced lipoxidation end products, advanced oxidation protein products (formed as a result of oxidative stress, carbonyl stress, or both), granulocyte inhibitory proteins, or leptin. Currently available membrane materials do not provide long-lasting, effective reduction of middle molecules in patients who require maintenance hemodialysis.
Hörl
Walter H
WH
Department of Medicine, Division of Nephrology, University of Vienna, Vienna, Austria. walter.hoerl@nephro.imed3.akh-wien.ac.at
D001672:Biocompatible Materials; D006801:Humans; D007378:Interleukins / Q000097:blood*; D008567:Membranes, Artificial; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D006435:Renal Dialysis / Q000295:instrumentation*; D014118:Toxins, Biological / Q000097:blood*
D001672:Biocompatible Materials; D007378:Interleukins; D008567:Membranes, Artificial; D014118:Toxins, Biological; C026865:uremia middle molecule toxins