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Clinical Relevance of Posttransplant DSAs in Patients Receiving Desensitization for HLA-incompatible Kidney Transplantation

Vo, Ashley A. PharmD1; Aubert, Olivier MD2; Haas, Mark MD, PhD3; Huang, Edmund MD1; Zhang, Xiaohai PhD4; Choi, Jua PharmD1; Peng, Alice MD1; Najjar, Reiad MD1; Sethi, Supreet MD1; Ammerman, Nori PharmD1; Lim, Kathlyn PharmD1; Jordan, Stanley C. MD1

doi: 10.1097/TP.0000000000002691
Original Clinical Science—General
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Background. Highly HLA-sensitized (HS) patients have an increased risk for the development of donor-specific antibodies (DSA) and antibody-mediated rejection (AMR) posttransplant. Here, we examined the risk for AMR in HS patients transplanted after desensitization (DES) who were DSA+ versus DSA− at transplant. We also examined the incidence and clinical impact of de novo DSAs (dnDSAs) and compared with dnDSA− patients.

Methods. From January 2013 to October 2016, 90 HS patients (PRA > 80%, DSA+ = 50 versus DSA− = 40) received kidney transplantation after DES with IVIG + rituximab ± PLEX (plasma exchange) ± tocilizumab. DSAs were monitored at transplant and at 1, 3, 6, 12, 24, 36, and 48 months posttransplant.

Results. Patients were divided into 4 groups: DSA+/+ (n = 31), DSA+/− (n=19), DSA−/+ (n=10), and DSA−/− (n = 30). Median follow-up time was 2.9 years. DSA-negative patients who developed dnDSA had the highest incidence of AMR (70%) compared with the DSA+/+ (45%), DSA+/− (11%), and DSA−/− (10%) patients (P < 0.0001). Among patients who developed AMR, Banff 2013 AMR scores did not differ among the 4 groups. Graft survival and estimated glomerular filtration rate determinations at 4 years were similar.

Conclusions. Persistence of preexisting DSAs or development of dnDSA after transplant is associated with an increased risk for AMR. Despite this, we did not observe a difference in Banff biopsy scores, graft survival, or patient survival compared with those without DSAs after transplant. Thus, for HS patients undergoing HLA-incompatible kidney transplant, DES therapy and frequent monitoring for dnDSAs appears critical for good long-term survival in at-risk groups.

1 Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.

2 Paris Translational Research Center for Organ Transplantation, INSERM U970, Biostatistics Department, Paris, France.

3 Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA.

4 Department of HLA and Immunogenetics Lab, Cedars-Sinai Medical Center, Los Angeles, CA.

Received 10 August 2018. Revision received 3 January 2019.

Accepted 19 January 2019.

S.C.J. received grant/research support from Hansa Medical, Vitaeris, and Genentech. The authors declare no conflicts of interest.

A.A.V. and O.A. are cofirst authors.

A.A.V., O.A., and S.C.J. participated in research design, the writing of the paper, the performance of the research, and data analysis. M.H. participated in the writing of the paper. E.H. participated in the writing of the paper and data analysis. X.Z., J.C., A.P., R.N., S.S., N.A., and K.L. participated in the performance of the research.

Correspondence: Ashley A. Vo, PharmD, Cedars-Sinai Medical Center, 8900 Beverly Blvd., Los Angeles, CA 90048. (Ashley.vo@cshs.org).

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.