3654 ABO-INCOMPATIBLE KIDNEY TRANSPLANTATION LOWERS INCIDENCES OF DE NOVO DONOR-SPECIFIC ANTIBODIES AND CHRONIC ANTIBODY-MEDIATED REJECTION

Abstract Background and Aims ABO-incompatible kidney transplantation has been associated with an increased risk for antibody-mediated rejection (ABMR) and early graft loss attributable to isoagglutinins. Its impact on the development of de novo donor-specific HLA antibodies (DSA) and DSA-induced chronic ABMR, however, remains less well studied. Method We analyzed 297 kidney transplant recipients (KTRs) who underwent living donor transplantation at the University Hospital Zurich from 2009 to 2021. 58 ABO-incompatible (iABO) KTRs were compared to 239 ABO-compatible (cABO) KTRs concerning the development of de novo donor-specific antibodies (DSA) and antibody-mediated rejection (ABMR). ABO desensitization was performed using rituximab and antigen-specific immunoadsorption. The HLA-derived epitope-mismatches were calculated per HLA-locus and in total using the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm. High-resolution re-typing was performed from protocol kidney allograft biopsies if necessary. Results The incidence of TCMR/ABMR in the first post-transplant year was comparable between iABO KTRs (19%) and cABO KTRs (13%; p = 0.207). De novo DSA were detected in only 1 of 58 iABO KTRs but 12 of 239 cABO KTRs in the first post-transplant year and 2 of 58 iABO KTRs but 50 of 239 cABO KTRs in the long-term follow-up (p = 0.001). ABMR was diagnosed in only 1 of 58 iABO KTRs but 28 of 239 cABO KTRs after the first post-transplant year (p = 0.021). iABO kidney transplantation decreased the risk of de novo DSA development (HR 7.222, CI 1.755-29.722, p = 0.006) and ABMR (HR 7.362, CI 1.000-54.239; p = 0.050) after the first-post-transplant year independent from the presence of preformed DSA. Total PIRCHE-II scores and PIRCHE-II scores per locus were not associated with the development of de novo DSA in all 297 living-donor KTRs (p>0.05). Conclusion Our findings suggest that iABO kidney transplantation is associated with a lower incidence of de novo DSA and ABMR in the long term, independent from the HLA-derived epitope mismatch load. Whether this protective effect offers new therapeutic options against kidney allograft injury needs to be investigated in future studies.