Cold ischemia time: An independent predictor of increased HLA class I antibody production after rejection of a primary cadaveric renal allograft

Background. Cadaveric kidneys experiencing longer cold ischemia time (CIT) are associated with higher levels of delayed graft function, acute rejectio n, and early graft loss. One mechanism to explain these results is that isc hemia/reperfusion (I/R) injury makes the allograft more immunogenic by upre gulating 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 t ransplants (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) indep endently increased the risk of the AHG Class I PRA level being <greater tha n or equal to>20% after unsensitized patients rejected their first kidneys (relative risk=3.57; 95% confidence interval=1.26 to 10.14; P=0.01), despit e the same degree of Class I/II mismatch between the two CIT groups. The ov erall 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<gr eater than or equal to>15 hr group (46.3%+/-36.5; n=66) (P<0.001). Conclusion. Longer CIT induces a humorally more immunogenic kidney.