title: Cold ischemia time: an independent predictor of increased HLA class I antibody production after rejection of a primary cadaveric renal allograft.
abstract: BACKGROUND
  Cadaveric kidneys experiencing longer cold ischemia time (CIT) are associated with higher levels of delayed graft function, acute rejection, and early graft loss. One mechanism to explain these results is that ischemia/reperfusion (I/R) injury makes the allograft more immunogenic by upregulating molecules involved in the immune response (e.g., HLA Class I/II).
  
  
  METHODS
  We evaluated the influence of CIT on the production of HLA Class I antibody level, measured by an antihuman globulin panel reactive antibody (AHG PRA) level, in 90 unsensitized recipients of primary cadaveric renal transplants (from a total of 1442 between 1985 and 1997) who rejected their kidneys.
  
  
  RESULTS
  By multivariate analysis, a CIT of 15 hr or more (vs. < 15 hr) independently increased the risk of the AHG Class I PRA level being > or = 20% after unsensitized patients rejected their first kidneys (relative risk=3.57; 95% confidence interval=1.26 to 10.14; P=0.01), despite the same degree of Class I/II mismatch between the two CIT groups. The overall mean peak PRA level after primary kidney rejection was significantly lower for the CIT < 15 hr group (25.9%+/-33.9; n=24) compared with the CIT > or = 15 hr group (46.3%+/-36.5; n=66) (P<0.001).
  
  
  CONCLUSIONS
  Longer CIT induces a humorally more immunogenic kidney.
authors.affiliation: Midwest Transplant Network, Inc., Westwood, Kansas 66205, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Bryan
authors.forename: A M
authors.initials: AM
authors.lastname: Luger
authors.forename: J
authors.initials: J
authors.lastname: Martinez
authors.forename: N
authors.initials: N
authors.lastname: Muruve
authors.forename: P W
authors.initials: PW
authors.lastname: Nelson
authors.forename: G E
authors.initials: GE
authors.lastname: Pierce
authors.forename: G
authors.initials: G
authors.lastname: Ross
authors.forename: C F
authors.initials: CF
authors.lastname: Shield
authors.forename: B A
authors.initials: BA
authors.lastname: Warady
authors.forename: M I
authors.initials: MI
authors.lastname: Aeder
authors.forename: T S
authors.initials: TS
authors.lastname: Helling
mesh_terms: D000328:Adult; D000917:Antibody Formation; D002102:Cadaver; D003298:Coombs Test; D015925:Cryopreservation; D005260:Female; D005544:Forecasting; D006084:Graft Rejection / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007511:Ischemia / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008102:Liver Circulation; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I