Kidney transplant outcomes in HLA desensitized patients with pretransplant CDC and/or FCM positive crossmatches

Noble Johan^1,2Céline Dard³Diane Giovannini⁴Hamza Naciri Bennani¹Pierre Fournier³Béatrice Bardy³Anne Bourdin³Farida Imerzoukene¹Lionel Motte¹Florian Terrec¹Paolo Malvezzi¹Thomas JOUVE^1,2Lionel PE Rostaing^1,2*

• ¹Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, Centre Hospitalier Universitaire de Grenoble, Grenoble, Rhône-Alpes, France
• ²Université Grenoble Alpes, Saint Martin d'Hères, Auvergne-Rhone-Alpes, France
• ³HLA laboratory, Etablissement français du sang (EFS), La Tronche, France, La Tronche, France
• ⁴Histopathology Laboratory, Grenoble University Hospital, Grenoble, France, Grenoble, Rhône-Alpes, France

Background: Kidney transplant (KT) candidates with very high calculated panel reactive alloantibody (cPRA >95%) have limited chances to receive an HLA-matched transplant unless they undergo pretransplant desensitization.Objective: To assess the efficacy of immunoadsorption (IA) in desensitizing pretransplant KT candidates with high cPRA and positive crossmatch.Materials and methods: This was a single-center retrospective cohort study involving highly HLA-sensitized patients (cPRA >85%). Forty-nine patients underwent HLA-incompatible (HLAi) KT, of whom 25 (51%) received kidneys from deceased donors. Of these 49 patients, 23 had either a positive complement-dependent cytotoxic cross-match (CDC) and/or a positive flow cytometry cross-match (FCM). The remaining 26 patients had donor-specific anti-HLA (DSAs) detectable only by Luminex (CDC and FCM cross-matches were negative).Only CDC-positive and FCM-positive patients were desensitized. These 49 patients were compared with 160 patients who had cPRA >85% but underwent HLA-compatible (HLAc) KT, i.e., without pretransplant DSAs.Pretransplant desensitization included IA sessions, rituximab, tacrolimus, steroids, and mycophenolate mofetil. Induction therapy consisted of antithymocyte globulins.Results: The mean follow-up duration was 7.4 +/- 4 years. At 1-year and at last follow-up, 43 patient and death-censored graft survival rates were similar between HLAc and HLAi patients.However, HLAi patients experienced significantly more biopsy-proven rejections compared to HLAc patients. These rejections were predominantly antibody-mediated. Finally, the rate of infectious complications was similar between HLAc and HLAi patients. Conclusion: IA in addition to immunosuppression is an effective option for desensitizing HLAi patients, yielding favorable long-term outcomes. Abbreviations: ATG, antithymocyte globulins BPAR, biopsy-proven acute rejection caABMR, chronic active antibody-mediated rejection CDC, complement-dependent cytotoxicity cPRA, calculated panel-reactive alloantibodies DFPP, double filtration plasmapheresis DSA, donor-specific alloantibody DTT, Dithiothreitol FCM, flow cytometry HLA, human leukocyte antigen HLAc, HLA compatible kidney transplant HLAi, HLA incompatible kidney transplant HSP, highly sensitized patients IA, semi-specific immunoadsorption IVIG, polyclonal IV immunoglobulins KT, kidney transplant MFI, mean fluorescence intensity MMF, mycophenolate mofetil MPA, mycophenolic acid POD, post-operative day PP, plasmapheresis TGI, Taux de greffons incompatibles