Acute but transient release of terminal complement complex after reperfusion in clinical kidney transplantation.
BACKGROUND
Ischemia/reperfusion (I/R) injury has a major impact on kidney graft function and survival. Animal studies have suggested a role for complement activation in mediating I/R injury; however, results are not unambiguous. Whether complement activation is involved in clinical I/R injury in humans is still unclear.


METHODS
In the present study, we assessed the formation and release of C5b-9 during early reperfusion in clinical kidney transplantation in living donor, brain-dead donor, and cardiac dead donor kidney transplantation. By arteriovenous measurements and histologic studies, local terminal complement activation in the reperfused kidney was assessed.


RESULTS
There was no release of soluble C5b-9 (sC5b-9) from living donor kidneys, nor was there a release of C5a. In contrast, instantly after reperfusion, there was a significant but transient venous release of sC5b-9 from the reperfused kidney graft in brain-dead donor and cardiac dead donor kidney transplantation. This short-term activation of the terminal complement cascade in deceased-donor kidney transplantation was not reflected by renal tissue deposition of C5b-9 in biopsies taken 45 min after reperfusion.


CONCLUSIONS
This systematic study in human kidney transplantation shows an acute but nonsustained sC5b-9 release on reperfusion in deceased-donor kidney transplantation. This instantaneous, intravascular terminal complement activation may be induced by intravascular cellular debris and hypoxic or injured endothelium.
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. d.k.de_vries@lumc.nl
Dorottya K
DK
de Vries
Pieter
P
van der Pol
Gerritje E
GE
van Anken
Danielle J
DJ
van Gijlswijk
Jeffrey
J
Damman
Jan H
JH
Lindeman
Marlies E J
ME
Reinders
Alexander F
AF
Schaapherder
Cees van
Cv
Kooten
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy / Q000379:methods; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000033:anatomy & histology; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015424:Reperfusion / Q000379:methods*; D015427:Reperfusion Injury / Q000628:therapy; D014019:Tissue Donors
D015938:Complement Membrane Attack Complex