Human leukocyte antigens DR and AB and kidney retransplantation

Although class II human leukocyte antigen (HLA) DR mismatching has been shown to demonstrate a significant effect on kidney regraft survival, it has not generally been clinically emphasized.

We examined 2,574 kidney retransplants performed in Southeastern Organ Procurement Foundation centers between January 1988 and December 1997 in which there was ABDR typing on both donor and recipient and pretransplant panel reactive antibody (PRA) data.

Cox regression of multiple variables demonstrated that the most important risk factors in descending order were DR mismatching, non-white recipient, female donor, PRA as a continuous variable, and cold ischemia time. Although DR mismatching demonstrated a significant effect in white recipients, the impact was much greater in non-white recipients. In both groups, zero to four AB mismatches demonstrated no significant effect on regraft survival if DR was matched and only a minimal effect when DR was mismatched. The discrepancy of these findings with reports that demonstrate a stepwise decrease in regraft survival on the basis of the total zero to six ABDR mismatches was explained by the fact that the zero to six ABDR mismatches are a combination of AB mismatches with little effect and DR mismatches with a major effect. Regraft survival decreased progressively in association with increasing PRA.

DR matching is critically important in kidney retransplantation. There was no significant difference in survival of zero ABDR mismatched retransplants compared with one to four AB and zero DR mismatched retransplants. On the other hand, kidney graft survival of all one to four AB and zero DR mismatches exceeded that of one or two DR mismatched retransplants. We propose that the association of decreasing regraft survival with increasing PRA reflects undetected sensitization to class II, and possibly class I, antigens.