title: The additional detrimental effects of cold preservation on transplantation-associated injury in kidneys from living and brain-dead donor rats.
abstract: BACKGROUND
  Brain death and cold preservation are major alloantigen-independent risk factors for transplantation outcome. The present study was conducted to assess the influence of these factors on transplantation-associated injury independently or in combination.
  
  
  METHODS
  Brain death was induced in F344 rats. Renal grafts were harvested after 6 hr and either directly transplanted in unilateral nephrectomized Lewis recipient or subjected to 24 hr of cold preservation in University of Wisconsin solution before implantation. Allografts obtained from living donor rats were also subjected to cold preservation or not. DNA damage was assessed before implantation by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining. Ten days after transplantation, renal histology was performed according to Banff '97 classification. The expressions of cytokines and adhesion molecules were analyzed by quantitative polymerase chain reaction.
  
  
  RESULTS
  Cold preservation significantly increased the number of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling positive cells in renal allografts. Ten days after transplantation, histology revealed a higher degree of tubulitis and vasculitis scores when the grafts were subjected to cold storage. Vasculitis was aggravated when the graft was obtained from brain death (BD) donors. BD, but not cold preservation alone, was associated with papillary necrosis. This was more frequently observed after cold preservation. Immunohistology showed an increase in MHC class II+ cells after cold preservation. The combination of BD and cold preservation revealed a higher degree of VEGF and IL-10 expression.
  
  
  CONCLUSIONS
  Our Study emphasizes that cold ischemia time should be limited when renal allografts from brain-dead donors are transplanted.
authors.affiliation: Department of Medicine V (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany. simone.hoeger@urz.uni-heidelberg.de
authors.forename: Simone
authors.initials: S
authors.lastname: Hoeger
authors.forename: Kiril
authors.initials: K
authors.lastname: Petrov
authors.forename: Anke
authors.initials: A
authors.lastname: Reisenbuechler
authors.forename: Johann
authors.initials: J
authors.lastname: Fontana
authors.forename: Jochen
authors.initials: J
authors.lastname: Selhorst
authors.forename: Christine
authors.initials: C
authors.lastname: Hanusch
authors.forename: Grietje
authors.initials: G
authors.lastname: Beck
authors.forename: Marc A
authors.initials: MA
authors.lastname: Seelen
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van Son
authors.forename: Ruediger
authors.initials: R
authors.lastname: Waldherr
authors.forename: Peter
authors.initials: P
authors.lastname: Schnuelle
authors.forename: Benito A
authors.initials: BA
authors.lastname: Yard
mesh_terms: D000818:Animals; D001926:Brain Death; D003080:Cold Temperature; D015925:Cryopreservation / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007511:Ischemia; D007668:Kidney / Q000276:immunology / Q000293:injuries* / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D051381:Rats; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D004247:DNA