Kinetics of Pretransplant DSA, Post-Transplant Histology, and Graft Failure after Kidney Transplantation

A. Senev¹, E. Lerut², V. Van Sandt³, J. Callemeyn¹, M. Coemans¹, B. Sprangers², D. Kuypers², M. Emonds¹, M. Naesens²

¹Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium, ²University Hospitals Leuven, Leuven, Belgium, ³Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross-Flanders, Mechelen, Belgium

Meeting: 2019 American Transplant Congress

Abstract number: 116

Keywords: Graft survival, Histology, HLA antibodies, Kidney transplantation

Session Information

Session Name: Concurrent Session: Kidney Acute Antibody Mediated Rejection

Session Type: Concurrent Session

Date: Sunday, June 2, 2019

Session Time: 4:30pm-6:00pm

Presentation Time: 5:42pm-5:54pm

Location: Ballroom B

*Purpose: The association between the kinetics of pretransplant DSA levels and outcome after kidney transplantation is currently not well known. In this large cohort study (N=924 with 4260 post-transplant biopsies), we investigated the evolution and clinical significance of pretransplant donor specific antibodies (preDSA), positive with the single antigen beads assay but negative in complement-dependent cytotoxicity crossmatch.

*Methods: The donor specificity of the preDSA (N=107 patients with 500 biopsies) was determined by retrospective high-resolution genotyping of all donor-recipient pairs and evaluating all HLA A/B/C/DRB1/DRB345/DQA1/DQB1/DPA1 and DPB1 loci.

*Results: We found that in 52% of the patients with preDSA, the DSA spontaneously resolved within the first 3 months after transplantation, without receiving specific therapy for removal of the preDSA. PreDSA that persisted after transplantation had higher pretransplant MFI values (6143±4565 vs. 2874±2391, p<.0001) and more specificity against HLA class II (78.5%), especially against locus DQ (49%). Although patients with resolved and persistent preDSA both had a high incidence (53.6% and 58.8%, respectively) of histological picture of antibody-mediated rejection (ABMR_h) with similar histological appearance, the patients with preDSA that persisted after transplantation had worse 10-year graft survival compared to resolved preDSA and DSA-negative patients (43.9% vs. 81.2% vs. 87.4%, p<.0001). Compared to cases without DSA, Cox modeling revealed an increased risk of graft failure in the patients with persistent preDSA, in the presence (HR=8.3, p<.0001) but also in the absence (HR=4.3, p=0.001) of ABMR_h. In contrast, no increased risk of graft failure was seen in patients with resolved preDSA, again independent of the presence or absence of ABMR_h (HR=1.5, p=0.47 and HR=1.4, p=0.62, respectively).

*Conclusions: We conclude that persistence of preDSA after transplantation has a negative impact on graft survival, beyond the diagnosis of ABMR_h according to the current Banff classification. Even in the absence of antibody-targeting therapy, low-MFI DSA, and non-DQ DSA often disappear early after transplantation and are not deleterious for graft outcome, despite the association with transient histological abnormalities.

To cite this abstract in AMA style:

Senev A, Lerut E, Sandt VVan, Callemeyn J, Coemans M, Sprangers B, Kuypers D, Emonds M, Naesens M. Kinetics of Pretransplant DSA, Post-Transplant Histology, and Graft Failure after Kidney Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/kinetics-of-pretransplant-dsa-post-transplant-histology-and-graft-failure-after-kidney-transplantation/. Accessed November 22, 2024.

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