title: Deceased donor kidney transplantation across donor-specific antibody barriers: predictors of antibody-mediated rejection.
abstract: Apheresis-based desensitization allows for successful transplantation across major immunological barriers. For donor-specific antibody (DSA)- and/or crossmatch-positive transplantation, however, it has been shown that even intense immunomodulation may not completely prevent antibody-mediated rejection (ABMR).
  
  
  
  In this study, we evaluated transplant outcomes in 101 DSA+ deceased donor kidney transplant recipients (transplantation between 2009 and 2013; median follow-up: 24 months) who were subjected to immunoadsorption (IA)-based desensitization. Treatment included a single pre-transplant IA session, followed by anti-lymphocyte antibody and serial post-transplant IA. In 27 cases, a positive complement-dependent cytotoxicity crossmatch (CDCXM) was rendered negative immediately before transplantation. Seventy-four of the DSA+ recipients had a negative CDCXM already before IA.
  
  
  
  Three-year death-censored graft survival in DSA+ patients was significantly worse than in 513 DSA- recipients transplanted during the same period (79 versus 88%, P = 0.008). Thirty-three DSA+ recipients (33%) had ABMR. While a positive baseline CDCXM showed only a trend towards higher ABMR rates (41 versus 30% in CDCXM- recipients, P = 0.2), DSA mean fluorescence intensity (MFI) in single bead assays significantly associated with rejection, showing 20 versus 71% ABMR rates at <5000 versus >15 000 peak DSA MFI. The predictive value of MFI was moderate, with the highest accuracy at a median of 13 300 MFI (after cross-validation: 0.72). Other baseline variables, including CDC assay results, human leukocyte antigen mismatch, prior transplantation or type of induction treatment, did not add independent predictive information.
  
  
  
  IA-based desensitization failed to prevent ABMR in a considerable number of DSA+ recipients. Assessing DSA MFI may help stratify risk of rejection, supporting its use as a guide to organ allocation and individualized treatment.
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schwaiger
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria Alberta Transplant Applied Genomics Centre, ATAGC, University of Alberta, Edmonton, AB, Canada.
authors.forename: Farsad
authors.initials: F
authors.lastname: Eskandary
authors.affiliation: Department of Clinical Pathology, Medical University Vienna, Vienna, Austria.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kozakowski
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Bond
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: Željko
authors.initials: Ž
authors.lastname: Kikić
authors.affiliation: Transcriptome Sciences Inc., 250 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yoo
authors.affiliation: Center for Medical Statistics, Informatics and Intelligent Systems, Medical University Vienna, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Rasoul-Rockenschaub
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: Oberbauer
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology*; D001317:Austria / Q000453:epidemiology; D001781:Blood Component Removal / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000639:trends*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D006680:HLA Antigens
keywords: antibody-mediated rejection; crossmatch; donor-specific antibodies; immunoadsorption; kidney transplantation