Abstract
Highly sensitized kidney patients accrue on the transplant waiting list due to their broad immunization against non-self Human Leucocyte Antigens (HLA). Although challenging, the best option for highly sensitized patients is transplantation with a crossmatch negative donor without any additional therapeutic intervention. The Eurotransplant Acceptable Mismatch (AM) program was initiated more than 30 years ago with the intention to increase the chance for highly sensitized patients to be transplanted with such a compatible donor. The AM program allows for enhanced transplantation to this difficult to transplant patient group by allocating deceased donor kidneys on the basis of a match with the recipient’s own HLA antigens in combination with predefined acceptable antigens. Acceptable antigens are those HLA antigens towards which the patients has never formed antibodies, as determined by extensive laboratory testing. By using this extended HLA phenotype for allocation and giving priority whenever a compatible donor organ becomes available, organ offers are made for roughly 80% of patients in this program. Up till now, more than 1700 highly sensitized patients have been transplanted through the AM program. Recent studies have shown that the concept of acceptable mismatches being truly immunologically acceptable holds true for both rejection rates and long-term graft survival. Patients that were transplanted through the AM program had a similar rejection incidence and long-term graft survival rates identical to non-sensitized patients transplanted through regular allocation. However, a subset of patients included in the AM program does not receive an organ offer within a reasonable time frame. As these are often patients with a rare HLA phenotype in comparison to the Eurotransplant donor population, extension of the donor pool for these specific patients through further European collaboration would significantly increase their chances of being transplanted. For those patients that will not benefit from such strategy, desensitization is the ultimate solution.
Highlights
Sensitization against Human Leucocyte Antigens (HLA) occurs through pregnancy, blood transfusions or organ transplants
For the Eurotransplant population is has previously been shown that highly sensitized patients that were included in the Acceptable Mismatch (AM) program, but transplanted through regular allocation, had a markedly inferior graft survival compared to highly sensitized patients transplanted through the AM program [16].from March this year, patients included in the AM program will only receive organ offers through AM program allocation
When the AM program started in the late 1980’s, HLA typing was mainly done by serology, and HLA antibody specificities were determined by using complement dependent cytotoxicity (CDC) assays [17]
Summary
Sensitization against Human Leucocyte Antigens (HLA) occurs through pregnancy, blood transfusions or organ transplants. Sensitized patients awaiting a renal transplant are disadvantaged since their broad immunization status results in positive (virtual) crossmatches with almost all organ donors [1] Such broad immunization status precludes timely transplantation through regular deceased donor allocation schemes, which are based on the exclusion of donors carrying HLA to which the antibodies are directed (unacceptable antigens) [2]. One strategy for transplanting highly sensitized patients is to temporarily remove circulating antibodies and/or antibody production by desensitization treatment, creating a window of opportunity for transplantation of either a deceased or living donor organ in the presence of a negative crossmatch [4]. One would like to timely transplant highly sensitized patients without administering additional immunosuppressive drugs beyond the standard immunosuppressive protocols This is not possible if the allocation is based on unacceptable antigens. For the Eurotransplant population is has previously been shown that highly sensitized patients that were included in the AM program, but transplanted through regular allocation (exclusion of unacceptable antigens only), had a markedly inferior graft survival compared to highly sensitized patients transplanted through the AM program [16].from March this year, patients included in the AM program will only receive organ offers through AM program allocation
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