title: Early events in kidney donation: progression of endothelial activation, oxidative stress and tubular injury after brain death.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering/Artificial Organs, University Medical Center Groningen, The Netherlands. a.m.morariu@med.umcg.nl
authors.forename: Aurora M
authors.initials: AM
authors.lastname: Morariu
authors.forename: Theo A
authors.initials: TA
authors.lastname: Schuurs
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
authors.forename: Wim
authors.initials: W
authors.lastname: van Oeveren
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rakhorst
authors.forename: Rutger J
authors.initials: RJ
authors.lastname: Ploeg
mesh_terms: 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*