COLD ISCHEMIA TIME INCREASES HLA CLASS I ANTIBODIES AFTER REJECTION OF A PRIMARY CADAVERIC RENAL ALLOGRAFT

Abstract

679 Ischemic injury to kidneys up-regulates many of the molecules, cytokines, and co-stimulatory molecules that may precipitate, or be involved with an immune response to the kidney. Such up-regulation due to ischemic injury may contribute to delayed graft function (DGF) and/or acute rejection. To extend our understanding of the mechanism(s) involved in the injury/stress, inflammation, immunity triad, we measured the production of HLA Class I antibodies (PRA) in 90 recipients of primary cadaveric renal transplants done between 1985 and 1997 who were unsensitized before transplantation (each had at least 3 PRAs, all ≤9%); rejected their first kidney; and had at least three PRA tests performed after this rejection. The data in the table below show the effect of increasing cold ischemia time (CIT) of the rejected primary kidney on Class I antibody production.TableThe data show that Class I PRA levels are lower in the group of patients with CITs of less than 14 hours compared with each of the other CIT groups (< 0.02 for > 14 to ≤ 18; <0.001 for > 18 to ≤ 24; and <0.05 for ≥ 24 hours). The only other major influence on PRA levels was the number of HLA Class I mismatches between donor and recipient, with the 1 to 2 antigen mismatched group having lower PRA levels (28% ± 31; n=39) than those with 3 or 4 mismatches (51% ± 38; n=49) (p< 0.01). Furthermore, multivariate analysis showed that a CIT > 15 hours (odds ratio=3.5; 95% CI=1.2 to 10.1; p=0.01) and an HLA-A & B mismatch >2 (odds ratio=2.9; 95% CI=1.1 to 7.5; p=0.02) independently influenced the risk of developing anti-HLA Class I peak PRA > 20% after rejecting a first cadaveric kidney. Conclusion: These data suggest one additional explanation for the known association between CIT and DGF and/or acute rejection. They are also consistent with the possibility that once certain CIT levels are passed, the immunologic load induces more antibodies to donor HLA Class I antigens.