Malte Ziemann1, Wolfgang Altermann2, Katharina Angert3, Wolfgang Arns4, Anette Bachmann5, Tamam Bakchoul3, Bernhard Banas6, Annette von Borstel7, Klemens Budde8, Vanessa Ditt7, Gunilla Einecke9, Ute Eisenberger10, Thorsten Feldkamp11, Siegfried Görg3, Martina Guthoff12, Antje Habicht13, Michael Hallensleben14, Falko M Heinemann15, Nicole Hessler16, Christian Hugo17, Matthias Kaufmann18, Teresa Kauke19,20,21, Martina Koch22, Inke R König16, Christine Kurschat23, Claudia Lehmann24, Matthias Marget25, Anja Mühlfeld26, Martin Nitschke27, Luiza Pego da Silva28, Carmen Quick17, Axel Rahmel29, Thomas Rath30, Petra Reinke8, Lutz Renders31, Florian Sommer32, Bernd Spriewald33, Oliver Staeck8, Dirk Stippel34, Caner Süsal35, Bernhard Thiele36, Daniel Zecher6, Nils Lachmann37. 1. Institute for Transfusion Medicine and malte.ziemann@uksh.de. 2. Institute for Transfusion Medicine, University Hospital Halle, Halle, Germany. 3. Institute for Transfusion Medicine and. 4. Clinic for Internal Medicine I, Kliniken der Stadt Köln, Cologne, Germany. 5. Medical Department III - Endocrinology, Nephrology, Rheumatology and. 6. Department of Nephrology, University Hospital Regensburg, Regensburg, Germany. 7. Institute for Transfusion Medicine, Kliniken der Stadt Köln, Cologne, Germany. 8. Division of Nephrology and Internal Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany. 9. Clinic for Renal and Hypertensive Disorders and. 10. Clinic for Nephrology and. 11. Transplant Center, University Hospital of Schleswig-Holstein, Kiel, Germany. 12. Section for Renal and Hypertensive Disorders, Clinic for Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany. 13. Transplant Center. 14. Institute for Transfusion Medicine, Medizinische Hochschule Hannover, Hannover, Germany. 15. Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany. 16. Institute of Medical Biometry and Statistics, University Medical Center Schleswig-Holstein Lübeck, Germany. 17. Clinic for Internal Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany. 18. Regional Office North, German Organ Transplantation Foundation, Hannover, Germany. 19. Department of General, Visceral, Vascular, and Transplant Surgery and. 20. Department for Transfusion Medicine, Hospital of the Ludwig-Maximilians-University München München, Germany. 21. Department for Transfusion Medicine, Hospital of the Ludwigs-Maximilians-University München, München, Germany. 22. Department of Visceral Transplantation and. 23. Second Department of Internal Medicine, Transplant Center and. 24. Institute for Transfusion Medicine, University Hospital Leipzig, Leipzig, Germany. 25. Institute for Transfusion Medicine, University Hospital Hamburg, Hamburg, Germany. 26. Clinic for Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases, University Hospital Aachen, Aachen, Germany. 27. Transplant center, University Hospital of Schleswig-Holstein, Lübeck, Germany. 28. Department of Internal Medicine-Nephrology and. 29. German Organ Transplantation Foundation, Frankfurt, Germany. 30. Department for Nephrology and Transplantation, Westpfalz-Klinikum, Kaiserslautern, Germany. 31. Department for Nephrology, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany. 32. Department of General, Visceral, and Transplant Surgery, Klinikum Augsburg, Augsburg, Germany. 33. Department of Medicine 5 - Hematology and Oncology, University Hospital Erlangen, Erlangen, Germany. 34. Department of General, Visceral Surgery and Surgical Oncology, University Hospital Cologne, Cologne, Germany. 35. Institute of Immunology and Transplant Immunology, University Hospital, Heidelberg, Heidelberg, Germany. 36. Institut für Immunologie und Genetik Kaiserslautern, Kaiserslautern, Germany; and. 37. HLA Laboratory, Institute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
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.
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.
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