Successful cadaveric renal transplantation of patients highly sensitized to HLA Class I antigens

The purpose of our investigation was to evaluate long-term graft survival and the role of histocompatibility in patients who were highly sensitized to human leukocyte antigen (HLA) Class I antigens and received a cadaveric renal transplant. Our multi-institutional study evaluated 7-yr graft outcomes and the histocompatibility requirements of 61 (6.1%) highly sensitized (anti-human globulin panel reactive antibody [AHG PRA], greater than or equal to 80%) cadaveric renal transplantation patients, transplanted between 1988 and 1997, among 999 consecutive cadaveric renal transplants. One- and 7-yr graft survival in the high PRA group (n = 61) was 76 and 59%, and was not significantly different from that in the low PRA group (n = 938), 86 and 59% (Wilcoxon = 0.11; log-rank = 0.45) (died with a functioning graft [DWFG] not censored). When those data were divided into primary and regrafts, 1- and 7-yr graft outcomes for high and low PRA groups were not significantly different [(primary, 1- and 7-yr survival: high PRA = 83 and 74%, n = 30, and low PRA = 87 and 61%, n = 825; log-rank = 0.37 for DWFG not censored) (regrafts, 1- and 7-yr survival: high PRA = 70 and 42%, n = 31, and low PRA = 80 and 43%, n = 113; log-rank = 0.36 for DWFG not censored)]. We did observe a subgroup of the high PRA patient group that had inferior graft outcomes. Graft outcome at 1 and 6 yr in the high PRA group for patients who had one to two DR mismatches (65 and 50%, n = 41) was significantly worse than for high PRA patients who had zero DR mismatches with their donors (100 and 78%, n = 20) (log-rank = 0.01 for DWFG not censored). Furthermore, the mean number of HLA-A and -B mismatches was significantly greater in the high PRA/DR-mismatched group (1.7 +/- 1.2, n = 41) compared with the high PRA/zero DR-mismatched group (0.5 +/- 1.1, n = 19) (p < 0.001). Overall, these data suggest that the patient who is highly sensitized to HLA Class I antigens has a long-term p;raft outcome that is equivalent to less sensitized patients, but that HLA-DR mismatching and a higher degree of Class I mismatching may be poor prognostic indicators in such patients.