Early events in kidney donation: progression of endothelial activation, oxidative stress and tubular injury after brain death.
Cerebral injury leading to brain death (BD) causes major physiologic derangements in potential organ donors, which may result in vascular-endothelial activation and affect posttransplant graft function. We investigated the kinetic of pro-coagulatory and pro-inflammatory endothelial activation and the subsequent oxidative stress and renal tubular injury, early after BD declaration. BD was induced by slowly inflating a balloon-catheter inserted in the extradural space over a period of 30 min. Rats (n = 30) were sacrificed 0.5, 1, 2 or 4 h after BD-induction and compared with sham-controls. This study demonstrates immediate pro-coagulatory and pro-inflammatory activation of vascular endothelium after BD in kidney donor rats, proportional with the duration of BD. E- and P-Selectins, Aalpha/Bbeta-fibrinogen mRNA were abruptly and progressively up-regulated from 0.5 h BD onwards; P-Selectin membrane protein expression was increased; fibrinogen was primarily visualized in the peritubular capillaries. Plasma von Willebrand factor was significantly higher after 2 h and 4 h BD. Urine heart-fatty-acid-binding-protein and N-acetyl-glucosaminidase, used as new specific and sensitive markers of proximal and distal tubular damage, were found significantly increased after 0.5 h, with a maximum at 4 h. Unexpectedly, oxidative stress was detectable only late, after the installation of tubular injury, suggesting only a secondary role for hypoxia in triggering these injuries.
Morariu
Aurora M
AM
Department of Biomedical Engineering/Artificial Organs, University Medical Center Groningen, The Netherlands. a.m.morariu@med.umcg.nl
Schuurs
Theo A
TA
Leuvenink
Henri G D
HG
van Oeveren
Wim
W
Rakhorst
Gerhard
G
Ploeg
Rutger J
RJ
D001926:Brain Death; D001930:Brain Injuries / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D007668:Kidney; D007684:Kidney Tubules / Q000473:pathology* / Q000502:physiology; D018384:Oxidative Stress; D011180:Postmortem Changes; D014019:Tissue Donors; D009927:Tissue and Organ Procurement / Q000379:methods*