European Guideline for the Management of Kidney Transplant Patients With HLA Antibodies: By the European Society for Organ Transplantation Working Group

Abstract

This guideline, from a European Society of Organ Transplantation (ESOT) working group, concerns the management of kidney transplant patients with HLA antibodies. Sensitization should be defined using a virtual parameter such as calculated Reaction Frequency (cRF), which assesses HLA antibodies derived from the actual organ donor population. Highly sensitized patients should be prioritized in kidney allocation schemes and linking allocation schemes may increase opportunities. The use of the ENGAGE 5 ((Bestard et al., Transpl Int, 2021, 34: 1005–1018) system and online calculators for assessing risk is recommended. The Eurotransplant Acceptable Mismatch program should be extended. If strategies for finding a compatible kidney are very unlikely to yield a transplant, desensitization may be considered and should be performed with plasma exchange or immunoadsorption, supplemented with IViG and/or anti-CD20 antibody. Newer therapies, such as imlifidase, may offer alternatives. Few studies compare HLA incompatible transplantation with remaining on the waiting list, and comparisons of morbidity or quality of life do not exist. Kidney paired exchange programs (KEP) should be more widely used and should include unspecified and deceased donors, as well as compatible living donor pairs. The use of a KEP is preferred to desensitization, but highly sensitized patients should not be left on a KEP list indefinitely if the option of a direct incompatible transplant exists.

Tocilizumab Evaluation in HLA-Desensitization before Kidney Transplantation as an Add-On Therapy to Apheresis: The TETRA Study

“…We prospectively included kidney transplant candidates who had elevated levels of calculated panel-reactive antibodies (of >80%) and no potential living kidney donor, or candidates who had (a) donor-specific HLA antibody(ies) (DSA) against their future donor (in cases with a living donor) and had been referred to our center for HLA desensitization before kidney transplantation (KT). Following the ENGAGE guidelines [ 10 , 11 ], all patients receiving a kidney from a living donor started from category 1 (cross-match positive) before desensitization and reached category 2–3 (lymphocytotoxicity [LCT] cross-match negative, historical DSA), while patients receiving a kidney from a deceased donor started from category 1–3 (DSA positive before desensitization) and reached category 2–3.…”

Strategies to Overcome HLA Sensitization and Improve Access to Retransplantation after Kidney Graft Loss

“…If these antibodies are directed against an highly frequent antigen, it extremely restricts the chance of finding a donor [ 39 ]. The 2022 European Guideline for the Management of Kidney Transplant Patients with HLA Antibodies recommends that defining unacceptable mismatches in highly sensitized patients on the base of weak antibody reactivity in solid-phase assays must be cautious and weight the poorly defined risk of antibody-mediated versus prolonged waiting time and associated mortality and morbidity [ 16 ].…”

“…The European Guideline for the Management of Kidney Transplant Patients with HLA Antibodies, published in 2022, recommends an active policy of prioritizing highly sensitized patients for organ transplantation. For patients without an available living donor, prioritization schemes and acceptable mismatch programs are the first options [ 16 ].…”

“…Several groups are focusing on the management of the failing graft and strategies to increase the transplant success on the sensitized patients are highlights in the KT community, with new recommendations and guidelines being published [ 15 , 16 ].…”

Chimeric HLA antibody receptor T cells for targeted therapy of antibody‐mediated rejection in transplantation

“…Currently, there are several desensitization protocols, which can include the elimination of DSA through plasma exchange or immunoadsorption and subsequent immunoglobulin replacement. 17 In some centers, the elimination of B cells using anti-CD20 antibodies, or proteasome inhibitors (bortezomib or carfilzomib) to eliminate plasma cells has been assessed to eliminate the antibody-producing cells. 18 These therapies have also been used to treat ABMR 19 with variable success rates; in some patients, a remission of the rejection episode can be achieved, but in others, an acute or chronic deterioration of graft function with subsequent graft loss persists.…”