REPEATED HLA MISMATCHES AND 2ND RENAL GRAFT-SURVIVAL IN CENTERS OF THE SOUTH-EASTERN-ORGAN-PROCUREMENT-FOUNDATION

To determine if repeated HLA mismatches and other putative risk factor s were predictive of second graft failure in second grafts performed a t Southeastern Organ Procurement Foundation (SEOPF) member centers, we identified a cohort of 753 retransplants in which one or more HLA ant igens were mismatched in primary grafts. Of this group, 158 (21.1%) re ceived second grafts with repeated mismatches of one or more HLA-A, B, or DR antigens that were previously mismatched in the primary graft ( RMMs). All regrafts were cadaveric kidneys transplanted between 1982 a nd 1995. Multivariate analysis of 19 covariates in 438 regrafts identi fied four independent factors that were predictive of graft survival f requency in second transplants. Three of the four factors were associa ted with a reduced risk for graft loss in retransplants: cyclosporin A (CsA) use in regrafts (p=0.0001, RR=0.26), peak PRA<50% (p=0.008, RR= 0.52) and white donor race (p=0.035, RR=0.63). One factor was associat ed with an increased risk of second graft failure, namely, blood trans fusion prior to the first graft (p=0.026, RR=5.14). None of the other 15 factors exerted significant additional risk to regraft survival fre quency in these SEOPF data. In multivariate analysis, RMMs were not as sociated with altered graft survival frequency in regrafts (p=0.944, R R=0.99). We then used univariate analyses to determine whether RMMs ha d adverse effects on GS in particular subsets of recipients that were thought to be at increased risk for the second transplant failure. Uni variate analyses were performed with methods that are sensitive to ear ly events (Wilcoxon) and late events (log-rank), The variables tested were CsA use for the regraft, duration of primary graft function, pane l reactive antibody levels (PRA), immunopathologic cause of first graf t failure, and HLA mismatch of the second graft. These analyses indica ted that repeated HLA mismatches were not an associated risk factor in any of these subgroups, These SEOPF data indicate that RMMs are not p redictive of increased frequency of graft loss in cadaveric donor seco nd transplants. We conclude that our results do not support a policy o f routine avoidance of RMMs, which may result in increased waiting tim e for a second donor without providing an improved graft survival rate . The available literature suggests that HLA antibody identification, the use of sensitive flow cytometric and antiglobulin-augmented cross- match tests, together with appropriate donor selection, optimal immuno suppression and patient management may be sufficient to avoid the earl y loss of second grafts.