Local renal complement C3 induction by donor brain death is associated with reduced renal allograft function after transplantation.
BACKGROUND
Kidneys derived from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Strikingly, early and profound serum levels of IL-6 in brain-dead donors are observed. IL-6 is the main regulator of the acute phase response (APR). The aim of this translational study was to investigate the expression of renal acute phase proteins (APPs) following brain death (BD) and to assess the association with renal allograft outcome after transplantation.


METHODS
BD was induced in rats by inflating a subdurally placed balloon catheter. Kidney biopsies were obtained from human living and brain-dead donors at donation, after cold preservation and reperfusion. In vitro, renal proximal tubular epithelial cells (HK-2 cells) were stimulated with IL-6.


RESULTS
Both in human and rat brain-dead donors, C3 and FBG expression was enhanced at donation compared to living donors and sham-operated animals. In human donors, no additional expression was found after cold ischaemia or reperfusion. C3 expression after reperfusion was independently associated with decreased short-term function after transplantation in grafts from brain-dead donors. In cultured HK-2 cells, C3 production was induced in the presence of IL-6.


CONCLUSIONS
In conclusion, BD induces renal C3 and FBG expression. Moreover, C3 expression is associated with a worse allograft function early after transplantation. Therefore, targeting renal APPs in brain-dead donors, especially complement C3, may improve transplant outcome.
Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands. j.damman@chir.umcg.nl
Jeffrey
J
Damman
Willemijn N
WN
Nijboer
Theo A
TA
Schuurs
Henri G
HG
Leuvenink
Aurora M
AM
Morariu
Stefan G
SG
Tullius
Harry
H
van Goor
Rutger J
RJ
Ploeg
Marc A
MA
Seelen
D000328:Adult; D000818:Animals; D015153:Blotting, Western; D001926:Brain Death / Q000503:physiopathology*; D050377:Cold Ischemia; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D011951:Receptors, Complement / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D020858:Tissue and Organ Harvesting
D003176:Complement C3; D015850:Interleukin-6; D012333:RNA, Messenger; D011951:Receptors, Complement