Effect of Blood Transfusion on Renal Allograft Survival: Immunologic Considerations

Abstract

DETERMINATION of immunologic factors relevant to renal allograft survival may allow identification of high risk potential recipients who will experience poor allograft survival. These factors may include histocompatibility matching, determination of recipient anti donor immune responsiveness and finally, the general, nonspecific state of recipient immunocompetence. Well matched cadaveric grafts, in recipients with no known donor alloantigen pre sensitivity , may be rejected because the recipient is a high-risk strong immune responder. 1 We cannot yet determine whether these recipients are strong responders to all alloantigens or whether they are presensitized to a donor antigen not tested for, such as kidney specific or enothelial antigens. For recipients of living related donor (LRD) organs a high donor specific mixed lymphocyte culture (MLC) stimulation index (SI) is a risk factor. As has been reported by the UCSF transplant group and others, graft survival, in haplotype matched related renal allograft recipients with a high MLC SI, is comparable to the results of cadaveric transplantation with a l-yr graft survival rate of 45%-55%.2 The data imply that high MLC responders are at risk when they receive the LRD organ. Potential recipients of LRD grafts, with strong donor specific MLC responsiveness, may be relegated to receive a cadaveric allograft as one alternative. A second alternative is to be transplanted with the LRD graft and to be treated with adjunctive immunosuppressive medications postoperatively, such as antithymocyte globulin (ATG) or cyclosporin A, to dampen the potentially destructive immune response. These medications may modify the immune response and improve strong immune responder graft survivals so that they are comparable to weak MLC LRD graft survivals. 1 However, the patient morbidity and mortality attendant with the use of these medications is still to be determined. A third alternative is for the strong MLC responder recipient to be treated with purposeful blood transfusions from the prospective kidney donor prior to transplant. Transfused recipients who do not respond by developing deleterious anti-Tor B antibodies can be transplanted and a clear cut positive influence on allograft survival has been reported. 3•4 However, before recommending wholesale donor specific transfusions (DST) of strong responder recipients of LRD grafts, a detailed examination of the protocol is necessary to determine the appropriateness of such a protocol to other patients and to compare these data with data obtained from random donor transfusions in cadaveric transplantation. It is possible that consideration of these points may result in an appreciation of what has been accomplished, arid more significantly, may direct our attention to improving graft survival for those positive responders who are excluded from receiving an LRD graft following transfusion and for recipients of cadaveric grafts. Since initiating the DST protocol, the UCSF transplant team has reported that approximately 30% of the transfused patients developed donor specific anti-T or B antibodies, which was taken as a contraindication to transplantation. Recipients v.'ith a negative cross-match who received a kidney from their blood donors had approximately a 95% graft survival. 3.4 As indicated, the mechanism(s) operative in the DST protocol may be: (1) selection and segregation of responders from nonresponders by antibody development; or (2) modification of the host immune response by the development of suppressor cells or the development of antiidiotypic (enhancing) antibodies. As reported, approximately 65% of the patients receiving DST also received random donor transfusions. 3 It is now widely accepted that increasing numbers of random pretransplant transfusions can improve cadaveric allograft survival. 5 Moreover, haplotype matched recipients of LRD