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

Abstract

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], > or = 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 graft 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.

Humoral Theory of Transplantation

“…Moreover, this effect was even more marked in patients who had previously rejected a transplant. In the intervening 30 years, many publications have reconfirmed the fact that antibodies, as a measure of presensitization, are important for kidney (14–26), heart (27–30), liver (31–34) and lung (5) transplants.…”

HLA phenotypes of ESRD patients are risk factors in the panel‐reactive antibody (PRA) response

“…Increasing PRA levels are associated with increasing odds of graft failure (6,7), despite the use of crossmatch tests to avoid transplantation when donor-specific HLA antibodies are detected in the transplant candidate. The negative impact of PRA on outcome is further exaggerated with increasing HLA mismatch (8).…”

A prospective 3‐yr evaluation of tacrolimus‐based immunosuppressive therapy in immunological high risk renal allograft recipients

“…Using an aggressive immunosuppressive combination, we demonstrated excellent 3‐yr patient and graft survival in a group of patients presenting multiple risk factors for rejection and ultimate allograft loss. The attributes of our patient group are congruent with the classification of ‘high risk’ for renal transplantation (1–5). Our findings should thus be generalizable to the larger population of highly sensitized renal transplant candidates.…”

“…However, mismatching and older donor organs did appear to be negative predictors of long‐term graft survival (17). Others however have shown a benefit of matching in highly sensitized recipients (5, 18). In our patient group, the paucity of living donors and the presence of some older donors may have been factors in the later graft losses.…”

“…Klouda et al (4) demonstrated a 70% 1 yr graft survival in highly sensitized recipients. More recently in a retospective review, Bryan et al (5) demonstrated 1 and 7 yr graft survival of 76% and 59% respectively in recipients with >80% PRA. However, in those with at least one haplotype DR mismatch survival decreased to 65% at 1 yr and 50% at 6 yr.…”