Preformed donor-specific HLA antibodies in living and deceased donor transplantation: A multicenter study

Malte Ziemann*, Wolfgang Altermann, Katharina Angert, Wolfgang Arns, Anette Bachmann, Tamam Bakchoul, Bernhard Banas, Annette von Borstel, Klemens Budde, Vanessa Ditt, Gunilla Einecke, Ute Eisenberger, Thorsten Feldkamp, Siegfried Görg, Martina Guthoff, Antje Habicht, Michael Hallensleben, Falko M. Heinemann, Nicole Hessler, Christian HugoMatthias Kaufmann, Teresa Kauke, Martina Koch, Inke R. König, Christine Kurschat, Claudia Lehmann, Matthias Marget, Anja Mühlfeld, Martin Nitschke, Luiza Pego da Silva, Carmen Quick, Axel Rahmel, Thomas Rath, Petra Reinke, Lutz Renders, Florian Sommer, Bernd Spriewald, Oliver Staeck, Dirk Stippel, Caner Süsal, Bernhard Thiele, Daniel Zecher, Nils Lachmann

*Corresponding author for this work
6 Citations (Scopus)

Abstract

Background and objectives The prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation. Design, setting, participants, & measurements The outcome of 4233 consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays. Using these screening results, DSA against HLA-A,-B,-C,-DRB1 and-DQB1 were determined. Data on clinical outcome and possible covariates were collected retrospectively. Results Pretransplant DSA were associated with lower overall graft survival, with a hazard ratio of 2.53 for living donation (95% confidence interval [95% CI], 1.49 to 4.29; P<0.001) and 1.59 for deceased donation (95% CI, 1.21 to 2.11; P=0.001). ABO-incompatible transplantation was associated with worse graft survival (hazard ratio, 2.09; 95% CI, 1.33 to 3.27; P=0.001) independent from DSA. There was no difference between DSA against class 1, class 2, or both. Stratification into DSA <3000 medium fluorescence intensity (MFI) and DSA ≥3000 MFI resulted in overlapping survival curves. Therefore, separate analyses were performed for 3-month and long-term graft survival. Although DSA <3000 MFI tended to be associated with both lower 3-month and long-term transplant survival in deceased donation, DSA ≥3000 MFI were only associated with worse long-term transplant survival in deceased donation. In living donation, only strong DSA were associated with reduced graft survival in the first 3 months, but both weak and strong DSA were associated with reduced long-term graft survival. A higher incidence of antibody-mediated rejection within 6 months was only associated with DSA ≥3000 MFI. Conclusions Preformed DSA were associated with an increased risk for graft loss in kidney transplantation, which was greater in living than in deceased donation. Even weak DSA <3000 MFI were associated with worse graft survival. This association was stronger in living than deceased donation.

Original languageEnglish
JournalClinical Journal of the American Society of Nephrology
Volume14
Issue number7
Pages (from-to)1056-1066
Number of pages11
ISSN1555-9041
DOIs
Publication statusPublished - 05.07.2019

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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