PUBLISHED BY
Strehler, Yara; Lachmann, Nils; Niemann, Matthias; Halleck, Fabian; Budde, Klemens; Pruß, Axel
PUBLISHED IN
Transfusion Medicine and Hemotherapy
PATIENTS
94
ABSTRACT
Introduction: Eurotransplant established the acceptable mismatch (AM) program to facilitate timely kidney transplantations of highly sensitized patients, but long-term granular clinical and immunological outcomes regarding overall graft survival and de novo DSA (dnDSA) formation are still intensively researched. The right choice of induction therapy in patients with differing immunological risk is not conclusively determined, as well as the impact of human leukocyte antigen (HLA) epitope matching on dnDSA formation. Methods: This monocentric, retrospective study analyzed 94 patients transplanted within the AM program between 2000 and 2019 compared to case-control matched cohorts of non- (PRA 0–5%; PRA-0) and intermediately sensitized (PRA 6–84%; PRA-6/84) patients transplanted through Eurotransplant Kidney Allocation System. Results: Estimated 10-year overall graft survival between the PRA-0 and AM cohorts was similar, whereas PRA-6/84 was significantly disadvantageous compared to PRA-0. Estimated 10-year incidence of antibody-mediated rejection rates was significantly lower in the PRA-0 group compared to AM and PRA-6/84 groups. Compared to the AM group, estimated incidence of de novo donor-specific antibody (dnDSA) was significantly lower in PRA-0 patients, with no differences between the AM and PRA-6/84 cohorts. The PRA-6/84 cohort was the only subgroup in which interleukin-2 receptor antagonist (IL2RA) induction was associated with longer overall graft survival, patient survival, and graft survival compared to depleting induction (ATG or OKT3). Broad HLA-A, -B, -DR mismatches (mmABDR) and HLA epitope mismatches determined by Eplets and PIRCHE-II were predictive for dnDSA formation in the total cohort, and the AM subgroup. Discussion: The high efforts expended on AM patients are justified to allow timely organ transplantation with acceptable risk profile and non-inferior outcomes. IL2RA induction in intermediately sensitized patients is associated with superior overall graft survival, patient survival, and graft survival compared to ATG/OKT3 induction, without negative effects on rejection episodes or dnDSA formation. In silico epitope matching might further help reduce dnDSA formation, particularly in high-risk AM patients.
HIGHLIGHTS
- The Eurotransplant AM (acceptable mismatch) program aids timely kidney transplants for highly sensitized patients, with ongoing research into long-term outcomes like graft survival and dnDSA formation.
- This study compared 94 AM patients (2000-2019) to non-sensitized (PRA 0-5%) and intermediately sensitized (PRA 6-84%) patients.
- Similar 10-year graft survival was found between non-sensitized and AM patients, but lower survival for intermediately sensitized patients. dnDSA incidence was lower in non-sensitized patients.
- IL2RA induction improved outcomes in intermediately sensitized patients over ATG/OKT3. HLA and epitope mismatches predicted dnDSA formation, suggesting in silico matching could reduce dnDSA in high-risk AM patients.
