[en] Highly sensitized (HS) kidney transplant (KTx) candidates, that is, typically considered internationally as those with panel-reactive antibody levels of >85%, remain a substantial subpopulation of patients with low chance of receiving a compatible organ. Among its many objectives, Eurotransplant-an international transplant organ allocation network serving 8 European countries-aims to improve the management of HS KTx candidates through its prioritized "acceptable mismatch" (AM) program. However, despite this program, some HS patients within the Eurotransplant network who have panel-reactive antibodies >85% still cannot access donor kidneys. For patients who remain in the AM program for ≥3 y without undergoing transplantation, an additional prioritization strategy has been implemented. This involves defining further AMs to allow for desensitization with imlifidase within the AM program. While the AM desensitization program was being developed, the Belgian Imlifidase Scientific Expert Group within the Eurotransplant network independently recognized the need for guidelines on imlifidase desensitization for real-world use in HS KTx candidates (including both AM and Eurotransplant Kidney Allocation System patients). This article describes the consensus guidelines they subsequently developed, which represent a model that any center within the Eurotransplant region could adapt or apply in clinical practice when treating HS KTx candidates who require imlifidase desensitization. The consensus guidelines include patient eligibility criteria for imlifidase treatment that align with Eurotransplant allocation rules and incorporate posttransplant management strategies for HS patients. These guidelines are dynamic and will be reviewed and updated regularly as Eurotransplant rules change and imlifidase experience grows.
Disciplines :
Urology & nephrology
Author, co-author :
Kuypers, Dirk R J; Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Belgium ; Department of Microbiology, Immunology and Transplantation, University Hospitals Leuven, Belgium
Claas, Frans H J; University Hospitals Antwerpen, Antwerp, Belgium ; Leiden University Medical Center, Leiden, the Netherlands
Bouquegneau, Antoine ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie
Buemi, Antoine; University Clinic Saint-Luc, Brussels, Belgium
de Fijter, Johan W; University Hospitals Antwerpen, Antwerp, Belgium
Emonds, Marie-Paule; Red Cross-Flanders, Mechelen, Brussels
Gambino, Giuseppe; University Hospitals Brussels, Belgium
Gervais, Thibaut; University Clinic Saint-Luc, Brussels, Belgium
Gothot, André ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la coagulation et de l'hémostase
Holovska, Vanda; University Hospitals Brussels, Belgium
Le Moine, Alain; University Hospitals Brussels, Belgium
Massart, Annick; University Hospitals Antwerpen, Antwerp, Belgium
Mikhalski, Dimitri; University Hospitals Brussels, Belgium
Naesens, Maarten; Department of Microbiology, Immunology and Transplantation, University Hospitals Leuven, Belgium
Pipeleers, Lissa; University Hospitals Brussels, Belgium
Schmitt, Justine ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la coagulation et de l'hémostase
Streel, Corentin; University Clinic Saint-Luc, Brussels, Belgium
Van Laecke, Steven; University Hospital Gent, Gent, Belgium
Weekers, Laurent ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie
Wissing, Karl Martin; University Hospitals Brussels, Belgium
Kanaan, Nada; University Clinic Saint-Luc, Brussels, Belgium
Mamode N, Bestard O, Claas F, et al. European guideline for the management of kidney transplant patients with HLA antibodies: by the European Society for Organ Transplantation Working Group. Transpl Int. 2022;35:1-16.
Jackson KR, Motter JD, Kernodle A, et al. How do highly sensitized patients get kidney transplants in the United States? Trends over the last decade. Am J Transplant. 2020;20:2101-2112.
Heidt S, Claas FHJ. Transplantation in highly senstitized patients: challenges and recommendations. Expert Rev Clin Immunol. 2018;14:673-679.
Eurotransplant International Foundation. Statistics Report Library (2024). Available at https://statistics.eurotransplant.org. Accessed November 26, 2024.
Ferrari P, Weimar W, Johnson RJ, et al. Kidney paired donation: principles, protocols and programs. Nephrol Dial Transplant. 2015;30:1276-1285.
Heidt S, Haasnoot GW, van der Linden-van Oevelen MJH, et al. Highly sensitized patients are well served by receiving a compatible organ offer based on acceptable mismatches. Front Immunol. 2021;12:687254.
de Ferrante H, Smeulders B, Tieken I, et al. Immunized patients face reduced access to transplantation in the Eurotransplant Kidney Allocation System. Transplantation. 2023;107:2247-2254.
Perosa M, Ferreira GF, Modelli LG, et al. Disparity in the access to kidney transplantation for sensitized patients in the state of Sao Paulo-Brazil. Transpl Immunol. 2021;68:101441.
Noble J, Metzger A, Daligault M, et al. Immortal time-bias-corrected survival of highly sensitized patients and HLA-desensitized kidney transplant recipients. Kidney Int Rep. 2021;6:2629-2638.
Park Y, Ko EJ, Chung BH, et al. Kidney transplantation in highly sensitized recipients. Kidney Res Clin Pract. 2021;40:355-370.
Zecher D, Zeman F, Drasch T, et al. Impact of sensitization on waiting time prior to kidney transplantation in Germany. Transplantation. 2022;106:2448-2455.
Vo A, Ammerman N, Jordan SC. Advances in desensitization for human leukocyte antigen incompatible kidney transplantation. Curr Opin Organ Transplant. 2024;29:104-120.
Eurotransplant Manual. Version 2024.1 January 23, 2024. Chapter 4: Kidney (ETKAS and ESP). Available at https://www.eurotransplant.org/allocation/eurotransplant-manual/?highlight=Eurotransplant%20 Manual. Accessed April 10, 2025.
Idefirix® SmPC. Available at https://www.ema.europa.eu/en/documents/product-information/idefirix-epar-product-information_en.pdf. Accessed November 26, 2024.
Sethi S, Choi J, Toyoda M, et al. Desensititization: overcoming the immunologic barriers to transplantation. J Immunol Res. 2017;2017:6804678.
Jordan SC, Lorant T, Choi J, et al. Endopeptidase in highly sensitized patients undergoing transplantation. N Engl J Med. 2017;377:442-453.
Jordan SC, Legendre C, Desai NM, et al. Imlifidase desensitization in crossmatch-positive, highly sensitized kidney transplant recipients: results of an international phase 2 trial (highdes). Transplantation. 2021;105:1808-1817.
Kjellman C, Maldonado AQ, Sjöholm K, et al. Outcomes at 3 years post-transplant in imlifidase desensitized kidney transplant patients. Am J Transplant. 2021;21:3907-3918.
Mumford L, Fuggle SV, Martorell J, et al. A Europe wide acceptable mismatch program will enable transplantation of long waiting highly sensitized patients with a compatible donor. Transpl Immunol. 2021;64:101354.
Huang E, Maldonado AQ, Kjellman C, et al. Imlifidase for the treatment of anti-HLA antibody-mediated processes in kidney transplantation. Am J Transplant. 2022;22:691-697.
European Society for Organ Transplantation (ESOT). Management of transplant patients with HLA antibodies' Workshop Final Report. 14 April 2023, Vienna, Austria. Available at https://esot.org/wp-content/uploads/2023/07/ESOT_Workshop_Final_Report_Austria.pdf. Accessed November 26, 2024.
European Federation for Immunogenetics (EFI). Standards for histocompatibility and immunogenetics testing. Version 8. Available at https://efi-web.org/fileadmin/Efi_web/EFI_Standards_version_5_6. pdf. Accessed November 26, 2024.
Eurotransplant Manual. Version 5.5, July 9, 2024. Chapter 10 Kidney (histocompatibility). Available at https://www.eurotransplant.org/allocation/eurotransplant-manual/?highlight=Eurotransplant%20Manual. Accessed April 10 2025.
emc. Prograf® SmPC. Available at https://www.medicines.org.uk/emc/product/6720/smpc#gref. Accessed November 26, 2024.
emc. Advagraf® SmPC. Available at https://www.medicines.org.uk/emc/product/345/smpc#gref. Accessed November 26, 2024.
emc. CellCept® SmPC. Available at https://www.medicines.org.uk/emc/search?q=cellcept. Accessed November 26, 2024.
SoluMedrol® SmPC. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011856s103s104lbl.pdf. Accessed November 26, 2024.
Medrol® SmPC. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/011153s075lbl.pdf. Accessed November 26, 2024.
HPRA. Grafalon® SmPC. Available at https://www.fannin.eu/wp-content/uploads/2018/06/Grafalon-SPC.pdf. Accessed April 10, 2025.
Thymoglobulin® SmPC. Available at http://products.sanofi.us/thymoglobulin/thymoglobulin.pdf. Accessed November 26, 2024.
Milhès J, Marion O, Puissant B, et al. Impact of imlifidase treatment on immunoglobulins in an HLA-hypersensitized lupus nephritis patient with anti-SSA/SSB antibodies after kidney transplantation: a case report. J Transl Autoimmun. 2023;7:100223.
Schrezenmeier E, Choi M, Globke B, et al. Successful desensitization with imlifidase and daratumumab in a highly immunized, crossmatch positive, blood group-incompatible living-donor re-transplant recipient with systemic lupus erythematosus and antiphospholipid syndrome. Transfus Med Hemother. 2024;51:158-163.
Kamar N, Bertrand D, Caillard S, et al. Imlifidase in highly sensitized kidney transplant recipients with a positive crossmatch against a deceased donor. Kidney Int Rep. 2024;9:2927-2936.
Couzi L, Malvezzi P, Amrouche L, et al. Imlifidase for kidney transplantation of highly senstized patients with a positive crossmatch: the French consensus guidelines. Transplant Int. 2023;36:11244.
National Institute for Health and Care Excellence. Imlifidase for desensitisation treatment before kidney transplant in people with chronic kidney disease. Technology appraisal guidance. Reference number:TA809. July 20, 2022. Available at https://www.nice.org.uk/guidance/ta809. Accessed November 26, 2024.
Furian L, Bestard O, Budde K, et al. European consensus on the management of sensitized kidney transplant recipients: A Delphi Study. Transpl Int. 2024;37:12475.