Successful adaptation to organ allografting occurs under a variety of poorly understood conditions. The use of donor-specific antigen, administered intravenously under immunosuppressive coverage, to induce enhancement or tolerance in a large variety of allograft models is well established. More recently, there is an awareness of the beneficial effects of random blood tranfusion prior to human renal transplantation. The purpose of this project is to confirm previous pilot studies which indicate that administration of donor-specific blood products under immunosuppressive coverage prior to human renal allografting led to no evidence of sensitization and no immunologic graft loss in the postoperate period. One haplotype living-donor renal transplants, will be performed after a six to eight week course of oral azathioprine during which time the recipient will have received 600 ml of donor-specific blood in three aliquots. Immunologic monitoring will include: T- and B-cell crossmatches with temperature variants, ADCC crossmatch, direct CML, one-way MLC (cellular responsiveness), one-way MLC (indirect assay for serum blocking factors), li titer, heterophile titer, T- and B-cell autoantibody with temperature variants and monoclonal antibody characterization of T-cells. Testing will be performed before, and after transfusion and in the postrenal tranplantation period. Posternal transplantation immunosuppression will include azathioprine and prednisone. Randomized control groups will include: (1) neither intentional preoperative blood nor azathioprine treatment, and (2) azathioprine and non-donar-specific blood. Sensitization in the form of donor-specific warm T-cell lymphocytoxic antibody development will preclude transplantation. Results in the experimental and control groups will be analyzed with regard to: (1) allograft survival (absence of immunologic graft failure) at six months as a prediction of long-term function; (2) immunologic monitoring changes and the development of sensitization (warm donor-specific T-cell antibody) during the pretransplantation phase; and (3) during the postransplantation phase. A statistically significant improvement in allograft survival from donor-specific as opposed to non-donor-specific or no blood transfusions may eventually permit the use of related kidney donors with less than one haplotype match thus enlarging the potential pool of donors.
