Overview and epitope matching.

Abstract

1. Kidney graft survival rates have stabilized over the past 4 years, suggesting that gains achieved with CsA have plateaued. The overall 1-year graft survival is 77% for first cadaver donor transplants, 90% for parental donors, and 93% for HLA-identical sibling donors. Patient survival for all categories is now over 95%. 2. The UNOS 6-antigen match program has resulted in outstanding graft survivals. Of 88 kidneys which were transplanted into first graft recipients, the 6-antigen match kidney had a 1-year graft survival of 91% compared to 74% for the contralateral kidney transplanted locally (p less than 0.008). 3. In highly sensitized patients with more than 80% PRA the shipped 6-antigen matched kidney had a 91% 1-year graft survival rate compared to 72% survival in comparable control patients from the registry (p less than 0.005). In patients with less than 80% PRA, 6-antigen matched kidneys had 90% 1-year graft survival compared to 80% in controls (p less than 0.00001). 4. The spread of 1-year graft survival rates at 68 centers that performed more than 100 transplants was 63-94%. The cumulative graft survival of 6-antigen matches performed at 129 different centers was 90%. Thus, the strong center effect was neutralized by the use of matched transplants. 5. In contrast to the 1% of patients who would receive O-B,DR mismatched transplants on a random basis, if kidneys were shared in the national pool, 74% could receive such a transplant. We therefore propose that a keep one-share one policy be adopted for all kidneys harvested in the United States. If no 0-B,DR mismatched patient is available, both kidneys will be kept by the harvesting center. Since 63% of kidneys are currently being shared with other centers for various reasons, the 75% sharing suggested by the new system should not impose a hardship on transplant centers. The UNOS payback agreement will be replaced by this agreement by which shipping will be done only to achieve excellent matches. 6. In order to achieve a better method of excluding the worst mismatches, an attempt was made to develop a new method of mismatching using amino acid sequences of the HLA specificities. Donor and recipient types can be converted to amino acid sequences and the mismatching done on the basis of amino acids of mismatch at each residue or position. For each residue, specific combinations of amino acid substitutions were examined individually to determine their effect on graft survival. From these studies, a list of "immunogenic" amino acids was prepared, and graft survival was then computed for increasing numbers of amino acids of mismatch.(ABSTRACT TRUNCATED AT 400 WORDS)