title: Improvements in early behavior of rat kidney allografts after treatment of the brain-dead donor.
abstract: OBJECTIVE
  To improve the quality of organs from brain-dead donors by assessing the influence of alternative strategies on the early behavior of kidneys after transplantation into unmodified hosts.
  
  
  BACKGROUND
  Kidneys transplanted from living donors perform consistently better than those from cadaver sources. The authors have recently shown that donor brain death produces inflammatory changes in peripheral organs within hours, amplifies coincident ischemia-reperfusion injury, and accelerates acute and chronic rejection. Normalization of the graft by donor hormone treatment has hitherto been unsuccessful.
  
  
  METHODS
  A standardized rat model of brain death was used. Experimental groups included recipients of allogeneic grafts from living and brain-dead donors (F344-->LEW). Donors were treated immediately after induction of brain death either with intravenous steroids, which block inflammatory cytokine release, or a soluble P-selectin glycoprotein ligand (sPSGL), which blocks initial selectin-mediated cellular adhesion. Kidney grafts were examined serially up to 10 days by morphology, immmunohistology, and reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  Overall survival of ummodified recipients of kidneys from brain-dead donors was significantly reduced versus living donors. Animals with organs from brain-dead donors that had received steroids or sPSGL survived significantly longer than those from untreated brain-dead donors. The intensity of ischemia-reperfusion injury and of acute rejection was reduced. Cellular infiltration and transcription of mRNA of representative proinflammatory mediators were diminished.
  
  
  CONCLUSIONS
  Treatment of organ donors at the time of brain death markedly improves organ quality after kidney transplantation, upgrading it to that from a living donor.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Humboldt University Berlin, Charité, Campus Virchow, Augustenburgerplatz 1, 13353 Berlin, Germany. johann.pratschke@charite.de
authors.forename: J
authors.initials: J
authors.lastname: Pratschke
authors.forename: G
authors.initials: G
authors.lastname: Kofla
authors.forename: M J
authors.initials: MJ
authors.lastname: Wilhelm
authors.forename: A
authors.initials: A
authors.lastname: Vergopoulos
authors.forename: I
authors.initials: I
authors.lastname: Laskowski
authors.forename: G D
authors.initials: GD
authors.lastname: Shaw
authors.forename: S G
authors.initials: SG
authors.lastname: Tullius
authors.forename: H D
authors.initials: HD
authors.lastname: Volk
authors.forename: P
authors.initials: P
authors.lastname: Neuhaus
authors.forename: N L
authors.initials: NL
authors.lastname: Tilney
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001926:Brain Death; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology*; D006085:Graft Survival; D006681:HLA-D Antigens / Q000032:analysis; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014019:Tissue Donors
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D005938:Glucocorticoids; D006681:HLA-D Antigens; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein