Effects of brain death on stress and inflammatory response in the human donor kidney.
BACKGROUND
After kidney transplantation, a decreased graft survival is seen in grafts from brain dead donors compared to living donors, possibly related to a progressive inflammatory reaction in the graft. In this study, we focused on the effects of brain death on the inflammatory response (adhesion molecules, leukocyte infiltration, and gene expression) and stress-related heat shock proteins in the human kidney. Research outcomes and clinical donor parameters were linked to outcome data after transplantation.


METHODS
Human kidney biopsy specimens were obtained during organ retrieval from brain dead and living organ donor controls. On these specimens, immunohistochemistry and semiquantitative RT-PCR were performed. Regression analyses were performed connecting results to outcome data of kidney recipients.


RESULTS
In brain death, immunohistochemistry showed an increase of E-selectin and interstitial leukocyte invasion versus controls; RT-PCR showed an increase of gene expression of HO-1 and Hsp70. One and 3 years after transplantation, high ICAM and VCAM expression proved to have a negative effect on kidney function in brain dead and living kidneys, while HO-1 proved to have a strongly positive effect, but only in kidneys from living donors.


CONCLUSIONS
E-selectin expression and interstitial leukocyte accumulation in brain dead donor kidneys indicate an early phase inflammatory state prior to organ retrieval. Also, brain death causes a stress-related response resulting in upregulation of potentially protective heat shock proteins. The upregulation of HO-1 is beneficial in living donor kidneys, but might be inadequate in brain death.
Nijboer
W N
WN
Kidney Transplant Center, University Hospital Groningen, Groningen, The Netherlands. w.n.nijboer@chir.umcg.nl
Schuurs
T A
TA
van der Hoeven
J A B
JA
Leuvenink
H G D
HG
van der Heide
J J Homan
JJ
van Goor
H
H
Ploeg
R J
RJ
D001706:Biopsy; D001926:Brain Death; D018932:Chemokine CCL2 / Q000235:genetics; D019040:E-Selectin / Q000235:genetics; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D019520:Living Donors; D008565:Membrane Proteins; D009392:Nephrectomy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting / Q000379:methods; D016212:Transforming Growth Factor beta / Q000235:genetics; D016896:Treatment Outcome
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019040:E-Selectin; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D016212:Transforming Growth Factor beta; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1