AUTHOR=Kälble Florian , Süsal Caner , Pego da Silva Luiza , Speer Claudius , Benning Louise , Nusshag Christian , Pham Lien , Tran Hien , Schaier Matthias , Sommerer Claudia , Beimler Jörg , Mehrabi Arianeb , Zeier Martin , Morath Christian 

TITLE=Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption

JOURNAL=Frontiers in Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.781491

DOI=10.3389/fmed.2021.781491

ISSN=2296-858X

ABSTRACT=Due to the organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival.

Thirty-eight desensitized living donor kidney transplant recipients were included in the study. Nineteen patients had a positive CDC crossmatch result with their donor and 36 patients had Luminex-detected donor-specific HLA antibodies (DSA). The patients were successfully desensitized with a median of 8 immunoadsorption treatments; 12 patients received additional plasma exchange. After desensitization but before transplantation, the patients received the anti-CD20 antibody rituximab (N=36) in combination with thymoglobulin (N=20) or anti-IL2 receptor antibody (N=18). The results of the 38 desensitized patients were retrospectively compared to the results of 76 1:2-matched standard-risk recipients.

Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P=0.55 and P=0.16 respectively). There was a trend towards reduced death-censored graft survival in desensitized patients (P=0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P=0.43). 
The incidence of rejection episodes without borderline changes were with 21% in desensitized patients similar to 18% in standard-risk patients (P=0.74). 
Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85% and 81%, respectively, during pretransplant desensitization (P<0.001 for both). On day 360 after transplantation, 18 of 36 (50%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and de novo DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without de novo DSA had an AMR rate of 18% without graft loss.

Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss.