Immunized Patients Face Reduced Access to Transplantation in the Eurotransplant Kidney Allocation System

Abstract

Background. The presence of donor-specific HLA antibodies before transplantation is associated with poor transplantation outcomes. Unacceptable antigens can be assigned for Eurotransplant kidney transplant candidates to prevent kidney offers against which the candidate has developed clinically relevant HLA antibodies. This retrospective cohort study aimed to assess to what degree unacceptable antigens affect access to transplantation in the Eurotransplant Kidney Allocation System (ETKAS). Methods. Candidates who underwent kidney-only transplantation between 2016 and 2020 were included (n = 19 240). Cox regression was used to quantify the relationship between the relative transplantation rate and virtual panel-reactive antibodies (vPRAs), which is the percentage of the donor pool with unacceptable antigens. Models used accrued dialysis time as the timescale; were stratified by country and blood group of patient and were adjusted for nontransplantable status, patient age, sex, history of kidney transplantations, and prevalence of 0 HLA-DR–mismatched donors. Results. Transplantation rates were 23% lower for vPRA 0.1% to 50%, 51% lower for vPRA 75% to 85%, and decreased rapidly for vPRA of >85%. Prior studies showed significantly lower ETKAS transplantation rates only for highly sensitized patients (vPRA of >85%). The inverse relationship between transplantation rate and vPRA is independent of Eurotransplant country, listing time, and 0 HLA-DR–mismatched donor availability. Results were similar when quantifying the relationship between vPRA and attainment of a sufficiently high rank for an ETKAS offer, suggesting lower transplantation rates for immunized patients are due to current ETKAS allocation. Conclusions. Immunized patients face lower transplantation rates across Eurotransplant. The current ETKAS allocation mechanism inadequately compensates immunized patients for reduced access to transplantation.

Sensitive HLA antibody testing and the risk of antibody‐mediated rejection and graft failure

“…The above‐mentioned question regarding benefit of the sensitivity of the Luminex methods is of significant importance. Sensitive detection of HLA antibodies without great clinical importance could lead to the definition of many unacceptable HLA mismatches that do not impact graft longevity, but that affect access to transplantation 22 . The more unacceptable HLA mismatches, the less the potential donor kidney will be deemed suitable for a specific recipient.…”

“…However, studies have shown that even when pretransplant DSA led to a negative crossmatch, its significance as a determinant of poor graft outcomes remains 17,19,20 . Thus, unacceptable mismatches are avoided in the donor allocation process and frequently lead to exclusion of the donor organ—leading to increased time on the transplant waiting list for sensitised recipients 21,22 . However, the clinical significance of HLA antibodies that are discovered by more sensitive SAB technology, but not by CDC and/or ELISA, are still a matter of debate 23,24 …”

Significant Long‐Term Prevention of High Sensitization After Kidney Allograft Failure by Maintaining Calcineurin Inhibitor‐Based Immunosuppression

“…High sensitization is a major obstacle to retransplantation and increases WL times [12,14]; both French and German colleagues reported increased WL times and a decreased probability of KT in patients with PRA ≥85%, and even more evidently with PRA ≥95%. In the United States, after the KAS was introduced, offer rates increased for all cPRA groups, except for very highly sensitized patients, with an initial sharp rise for cPRA = 99%-100% patients, but a subsequent tapering of approximately 10% [11][12][13].…”

“…Over the last few decades, several strategies have been developed to mitigate the expected longer WL times in sensitized patients. However, broad national or international donor pool programs, kidney pair exchange, and desensitization protocols have shown minor benefits for very highly sensitized patients, namely those with panel reactive antibodies (PRA) > 98% [12,14]. Therefore, strategies to prevent high sensitization are urgently required.…”

Organtransplantation – Welche spenderspezifischen HLA-Antikörper sind akzeptabel?

“…In einer aktuellen Untersuchung von Eurotransplant zeigte sich bei deutschen Patienten in ETKAS bis zu einem vPRA von etwa 60% keine eindeutige Verschlechterung der Transplantationschancen (s. Fall 1). Ein vPRA über 85% war dagegen mit deutlich reduzierten Transplantationschancen assoziiert 3 .…”