e-Article
A porcine model of hemodialyzer reactions: roles of complement activation and rinsing back of extracorporeal blood.
Document Type
Academic Journal
Author
Pethő Á; Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary.; Piecha D; Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.; Mészáros T; SeroScience Ltd, Budapest, Hungary.; Urbanics R; SeroScience Ltd, Budapest, Hungary.; Moore C; Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.; Canaud B; Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.; School of Medicine, Montpellier University, Montpellier, France.; Rosivall L; International Nephrology Research and Training Center, Institute of Translational Medicine, Semmelweis University, Budapest, Hungary.; Mollnes TE; Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; Research Laboratory, Nordland Hospital Bodø and Faculty of Health Sciences and TREC, University of Tromsø, Tromsø, Norway.; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.; Steppan S; Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.; Szénási G; International Nephrology Research and Training Center, Institute of Translational Medicine, Semmelweis University, Budapest, Hungary.; Szebeni J; SeroScience Ltd, Budapest, Hungary.; Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, Budapest, Hungary.; Dézsi L; SeroScience Ltd, Budapest, Hungary.; Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, Budapest, Hungary.
Source
Publisher: Informa Healthcare Country of Publication: England NLM ID: 8701128 Publication Model: Print Cited Medium: Internet ISSN: 1525-6049 (Electronic) Linking ISSN: 0886022X NLM ISO Abbreviation: Ren Fail Subsets: MEDLINE
Subject
Language
English
Abstract
Hemodialysis reactions (HDRs) resemble complement-activation-related pseudoallergy (CARPA) to certain i.v. drugs, for which pigs provide a sensitive model. On this basis, to better understand the mechanism of human HDRs, we subjected pigs to hemodialysis using polysulfone (FX CorDiax 40, Fresenius) or cellulose triacetate (SureFlux-15UX, Nipro) dialyzers, or Dialysis exchange-set without membranes, as control. Experimental endpoints included typical biomarkers of porcine CARPA; pulmonary arterial pressure (PAP), blood cell counts, plasma sC5b-9 and thromboxane-B2 levels. Hemodialysis (60 min) was followed by reinfusion of extracorporeal blood into the circulation, and finally, an intravenous bolus injection of the complement activator zymosan. The data indicated low-extent steady rise of sC5b-9 along with transient leukopenia, secondary leukocytosis and thrombocytopenia in the two dialyzer groups, consistent with moderate complement activation. Surprisingly, small changes in baseline PAP and plasma thromboxane-B2 levels during hemodialysis switched into 30%-70% sharp rises in all three groups resulting in synchronous spikes within minutes after blood reinfusion. These observations suggest limited complement activation by dialyzer membranes, on which a membrane-independent second immune stimulus was superimposed, and caused pathophysiological changes also characteristic of HDRs. Thus, the porcine CARPA model raises the hypothesis that a second "hit" on anaphylatoxin-sensitized immune cells may be a key contributor to HDRs.