title: Donor Desmopressin Treatment Does Not Affect Transplant Outcome in the Fischer to Lewis Rat Renal Transplant Model.
abstract: Retrospective studies suggest that donor desmopressin (DDAVP) treatment improves renal transplant outcome. The present study tests the hypothesis that desmopressin neutralizes the graft's endothelium from proinflammatory angiopoietin 2 containing Weibel-Palade bodies in the donor, resulting in reduced Weibel-Palade body release at the time of reperfusion in the recipient.
  
  
  
  Using rat models, we examined the influence of desmopressin treatment on the expression of vasopressin 2 receptors and adhesion molecules in brain-dead donors, with renal function examined in allogeneic recipients. The influence of desmopressin on the expression of adhesion molecules also was tested in vitro.
  
  
  
  Vasopressin 2 receptors were restricted to collecting ducts and distal tubules and only scarcely found in the renal vasculature. Vasopressin 2 receptor expression was down-regulated in brain-dead rats by desmopressin. Renal expression of vascular cellular adhesion molecule 1 and intercellular adhesion molecule 1 were significantly reduced in these rats. In contrast, angiopoietin 2 did not influence the expression of adhesion molecules in in vitro cultured endothelial cells after tumor necrosis factor ? stimulation. Donor desmopressin treatment improved neither renal function nor histology in allogeneic renal transplant recipients.
  
  
  
  Our data do not support the hypothesis that the clinically observed salutary effect of desmopressin is mediated by depletion of Weibel-Palade bodies in renal allografts.
authors.affiliation: From the Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Hospital Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Heiko M
authors.initials: HM
authors.lastname: Mundt
authors.forename: Simone
authors.initials: S
authors.lastname: Höger
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Waldherr
authors.forename: Peter
authors.initials: P
authors.lastname: Schnuelle
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
authors.forename: Benito A
authors.initials: BA
authors.lastname: Yard
authors.forename: Uwe
authors.initials: U
authors.lastname: Göttmann
authors.forename: Urs
authors.initials: U
authors.lastname: Benck
mesh_terms: D042702:Angiopoietin-2 / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D050377:Cold Ischemia / Q000009:adverse effects; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D023421:Models, Animal; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017483:Receptors, Vasopressin / Q000819:agonists / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D052096:Warm Ischemia / Q000009:adverse effects; D020302:Weibel-Palade Bodies / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D042702:Angiopoietin-2; C000609942:ICAM1 protein, rat; D017483:Receptors, Vasopressin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003894:Deamino Arginine Vasopressin