Document Detail

Extracorporeal ("ex vivo") connection of pig kidneys to humans. III. Studies of plasma complement activation and complement deposition in the kidney tissue.
MedLine Citation:
PMID:  9741455     Owner:  NLM     Status:  MEDLINE    
The complement system is one of the important factors involved in the hyperacute rejection of xenografts. This report deals with the activation of the complement system in a clinical trial where pig kidneys were extracorporeally connected to two volunteer dialysis patients who were pretreated with plasmapheresis in order to substantially reduce anti-pig xenoantibodies. The clinical data of the perfusion experiments and the patients humoral immune response to pig xenoantigens have been reported in detail (Xenotransplantation 1996; 3:328-339, 340-353). Three consecutive daily plasmapheresis treatments of the patients reduced the plasma complement protein (C3, C4, and C5) concentrations to 8-27% of the baseline values. The perfusion of the pig kidney connected to patient 1 was terminated at 65 min due to graft rejection and this patient was not hemodynamically affected by the experiment. The second experiment was terminated at 15 min due to an anaphylactic like reaction of the patient. In patient 1 a slight reduction of plasma C3, C4, and C5 and an increase of C5a and SC5b-9 occurred, while C3a decreased during the perfusion. Patient 2 had an increase of all complement parameters, most prominent for C4d and SC5b-9, which occurred concomitant with the appearance of the anaphylactic like side effects. In general, plasma levels of PMN elastase, IL6 and IL8 increased in both patients during the perfusion. Immunohistochemical investigation of the kidney tissues revealed deposition of human complement factors C1q, C4c, and C3c in a congruent pattern with the vasculature of the kidney in patient 1. In kidney 2 only trace amounts of C1q and C3c were found. Both kidneys were negative for properdin. Therefore, in this experimental set up with extracorporeal connection of pig kidneys to the human circulation the human complement cascade is activated mainly through the classical pathway.
A Bengtsson; C T Svalander; J Mölne; L Rydberg; M E Breimer
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Xenotransplantation     Volume:  5     ISSN:  0908-665X     ISO Abbreviation:  Xenotransplantation     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-11-17     Completed Date:  1998-11-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9438793     Medline TA:  Xenotransplantation     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  176-83     Citation Subset:  IM    
Department of Anesthesiology and Intensive Care, Sahlgrenska universitetssjukhuset, Göteborg, Sweden.
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MeSH Terms
Complement Activation*
Complement System Proteins / immunology*
Graft Rejection*
Kidney / immunology*
Kidney Transplantation / immunology*,  methods*
Middle Aged
Renal Dialysis
Transplantation, Heterologous
Reg. No./Substance:
9007-36-7/Complement System Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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