Application of an epitope‐based allocation system in pediatric kidney transplantation

Abstract

Donor-recipient HLA mismatch remains a leading cause for sensitization and graft loss in kidney transplantation. HLA compatibility at an epitope level is emerging as an improved method of matching compared with current HLA antigen allocation. A novel epitope-based allocation approach to prospectively exclude donors with high-level mismatches was implemented for pediatric KTRs on the DD waiting list. Nineteen consecutive transplants were followed for 12 months, including eight DD KTRs listed with eplet exclusions, as well as three DD KTRs and eight LD KTRs without exclusions. KTRs with eplet exclusions had estimated GFR of 78.5 mL/min/1.73 m , no episodes of rejection, and time to transplant 6.55 months. HLA-A, HLA-B, HLA-DR antigen mismatches were similar between all groups. KTRs with exclusions had significantly lower class II eplet mismatches (20.4) than the contemporary DD KTRs without exclusions (63.7) and DD KTRs transplanted in the preceding decade (46.9). dnDSAs were identified in two of eight DD KTRs with exclusions, two of three DD KTRs without exclusions and five of eight LD KTRs. Epitope-based allocation achieved timely access to transplantation, low class II eplet mismatches, and low rates of dnDSAs in the first year. This strategy requires longer follow-up and larger numbers, but has the potential to reduce anti-HLA sensitization and improve both graft survival and opportunities for future retransplantation.

Performance of an allele‐level multi‐locus HLA genotype imputation tool in hematopoietic stem cell donors from Quebec

“…In summary, while HaploStats may be used for imputing allele‐level HLA class I types in Caucasian Quebecer HSCD, it may contribute to greater misclassification of class II first two field HLA types. The growing interest in evaluating donor‐recipient compatibility at the epitope level and their role in predicting transplant outcomes make it imperative to ensure accurate allele‐level HLA type assignment . Despite the undeniable advantages of imputation tools, including the ability to decrease ambiguity at low cost and a quick turnaround time in comparison to resource‐intensive DNA‐based typing methods , our findings suggest that genotyping at the first two field level should be conducted whenever possible.…”

Allocation of deceased donor kidneys: A review of international practices

“…Alternatively, rather than promoting HLA matching in a minority of paediatric recipients, the Royal Children's Hospital in Melbourne, Australia established prospective exclusions of donors with HLA associated with high eplet mismatches for each individual patient. This approach significantly lowered class 2 eplet mismatches while a paediatric point bonus still allowed timely access to transplantation …”

Human leukocyte antigen eplet mismatches and long‐term clinical outcomes in pediatric renal transplantation: A pragmatic, registry‐based study

“…As a result, many children will require multiple transplants throughout their lives and therefore the proposed benefits of improved epitope matching are of particular importance in this patient population. These potential benefits have already prompted us, and other pediatric transplantation units, to integrate eplet matching into clinical practice 31‐33 . However, additional evidence is required to support the ongoing role of eplet matching in improving long‐term outcomes particularly when the potential benefits of improved immunological matching must be weighed against other factors in donor choice including donor age and organ quality.…”