Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation

Ziemann, Malte ; Altermann, Wolfgang ; Angert, Katharina ; Arns, Wolfgang ; Bachmann, Anette ; Bakchoul, Tamam ; Banas, Bernhard ; von Borstel, Annette ; Budde, Klemens ; Ditt, Vanessa ; Einecke, Gunilla ; Eisenberger, Ute ; Feldkamp, Thorsten ; Görg, Siegfried ; Guthoff, Martina ; Habicht, Antje ; Hallensleben, Michael ; Heinemann, Falko M. ; Hessler, Nicole ; Hugo, Christian ; Kaufmann, Matthias ; Kauke, Teresa ; Koch, Martina ; König, Inke R. ; Kurschat, Christine ; Lehmann, Claudia ; Marget, Matthias ; Mühlfeld, Anja ; Nitschke, Martin ; Pego da Silva, Luiza ; Quick, Carmen ; Rahmel, Axel ; Rath, Thomas ; Reinke, Petra

; Renders, Lutz ; Sommer, Florian ; Spriewald, Bernd ; Staeck, Oliver ; Stippel, Dirk

; Süsal, Caner ; Thiele, Bernhard ; Zecher, Daniel ; Lachmann, Nils

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Background and objectivesThe prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation.Design, setting, participants, & measurementsThe 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.ResultsPretransplant 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.ConclusionsPreformed 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.

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