Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Abstract

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long‐term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995‐2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6‐month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA‐B plus 1 HLA‐DR, or 2 HLA‐DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low‐risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.

Parsing the 100% calculated panel reactive antibody kidney transplant candidates: Who gets transplanted?

“…For hard to match candidates, convincing them to consider accepting Public Health Service (PHS) increased risk donors (25% of pool nationally), donors after cardiac death (DCD) (20% of pool nationally) and Hepatitis B core positive donors will improve chances of a match significantly. Although accepting ECD donors may be beneficial (10% of donors nationally) the acceptance of these donors is a more complex decision and one needs to consider the candidates desire to come off dialysis versus acceptance of a donor with a poorer outcome potentially leading to further sensitization …”

“…HLAMatchmaker has been used with success in Eurotranplant. 8,9 This approach determines acceptable HLA mismatches based on the epitopes of the HLA molecules of the candidate which are present on other HLA molecules not shared by the candidate. By determining acceptable mismatches, unacceptable mismatches can be surmised.…”

“…Although accepting ECD donors may be beneficial (10% of donors nationally) the acceptance of these donors is a more complex decision and one needs to consider the candidates desire to come off dialysis versus acceptance of a donor with a poorer outcome potentially leading to further sensitization. [9][10][11] For the highly sensitized population, time actively listed is very important. The unsensitized or mildly sensitized candidate must percolate up the list until they accumulate enough points to be competitive for an offer.…”

Novel insights into non‐HLA alloimmunity in kidney transplantation

“…The complexity that is introduced by the increasing number of genetically distinct HLA alleles that are recognized makes complete matching on the HLA antigen level impossible. The focus on a limited number of defined polymorphic residues proven to be targets of HLA antibodies may help to reduce complexity and improve matching of kidney allograft donors and recipients to prevent both (i) development of de novo donor specific antibodies (dnDSA) and (ii) identify acceptable mismatches in patients with already established donor specific antibody (DSA) .…”

Pre-existing Alloreactive T and B Cells and Their Possible Relevance for Pre-transplant Risk Estimation in Kidney Transplant Recipients

“…Furthermore, repeat transplantation candidates, as well as those with a history of pregnancy and multiple blood transfusions who have broad HLA sensitization tend to accumulate on transplant waitlists. These patients are not only difficult to pair with a crossmatch negative donor in order to be transplanted but are also more susceptible to develop T cell and/or antibody-mediated acute and chronic rejection unless special allocation algorithms or desensitization treatments are used (8)(9)(10)(11)(12).…”