Risk Stratification Before Living Donor Kidney Transplantation in Patients With Preformed Donor-specific Antibodies by Different Crossmatch Methods

Author:

Ziemann Malte1ORCID,Lindemann Monika2,Hallensleben Michael3,Altermann Wolfgang4,Althaus Karina56,Budde Klemens7,Einecke Gunilla8,Eisenberger Ute9,Ender Andrea10,Feldkamp Thorsten11,Grahammer Florian1213,Guthoff Martina14,Holzmann-Littig Christopher15,Hugo Christian16,Kauke Teresa171819,Kemmner Stephan19,Koch Martina20,Lachmann Nils21,Marget Matthias22,Morath Christian23,Nitschke Martin24,Renders Lutz15,Scherer Sabine25,Stumpf Julian16,Schwenger Vedat26,Sommer Florian27,Spriewald Bernd28,Süsal Caner25,Zecher Daniel29,Heinemann Falko M.2,Verboom Murielle3

Affiliation:

1. Institute for Transfusion Medicine, University Hospital of Schleswig-Holstein, Lübeck, Germany.

2. Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.

3. Institute for Transfusion Medicine, Medizinische Hochschule Hannover, Hannover, Germany.

4. Institute for Transfusion Medicine, University Hospital Halle, Halle, Germany.

5. Institute for Clinical and Experimental Transfusion Medicine, University Hospital of Tübingen, Tübingen, Germany.

6. Center for Clinical Transfusion Medicine, Tübingen, Germany.

7. Medizinische Klinik m. S. Nephrologie, Charité–Universitätsmedizin Berlin, Berlin, Germany.

8. Klinik für Nieren- und Hochdruckerkrankungen, Medizinische Hochschule Hannover, Hannover, Germany.

9. Klinik für Nephrologie, University Hospital Essen, Essen, Germany.

10. Institute for Transfusion Medicine, Klinikum der Landeshauptstadt Stuttgart, Stuttgart, Germany.

11. Transplant Center, University Hospital of Schleswig-Holstein, Kiel, Germany.

12. III. Medizinische Klinik und Poliklinik für Nephrologie, Rheumatologie und Endokrinologie, University Hospital Hamburg Eppendorf, Hamburg, Germany.

13. Hamburg Center for Kidney Health, University Hospital Hamburg Eppendorf, Hamburg, Germany.

14. Medizinische Klinik IV, Sektion Nieren- und Hochdruckkrankheiten, University Hospital Tübingen, Tübingen, Germany.

15. Nephrologie, Klinikum Rechts der Isar, Technische Universität München, München, Germany.

16. Medizinische Klinik III, University Hospital Carl Gustav Carus, Dresden, Germany.

17. Abteilung für Transfusionsmedizin, Zelltherapeutika und Hämostaseologie, Labor für Immungenetik, Klinik für Anästhesiologie, Klinikum der Universität München, München, Germany.

18. Abteilung Thoraxchirurgie, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Klinikum der Universität München, München, Germany.

19. Transplant Center, Klinikum der Universität München, München, Germany.

20. Hepatobiliäre Chirurgie und Transplantationschirurgie, University Hospital Hamburg, Hamburg, Germany.

21. HLA-Labor, Charité–Universitätsmedizin Berlin, Berlin, Germany.

22. Institute for Transfusion Medicine, University Hospital Hamburg, Hamburg, Germany.

23. Zentrum für Innere Medizin, Nephrologie, University Hospital Heidelberg, Heidelberg, Germany.

24. Transplant Center, University Hospital of Schleswig-Holstein, Lübeck, Germany.

25. Institut für Immunologie, Transplantationsimmunologie, University Hospital Heidelberg, Heidelberg, Germany.

26. Klinik für Nieren-, Hochdruck- und Autoimmunerkrankungen, Klinikum der Landeshauptstadt Stuttgart, Stuttgart, Germany.

27. Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, University Hospital Augsburg, Augsburg, Germany.

28. Medizinische Klinik 5–Hämatologie und Internistische Onkologie, University Hospital Erlangen, Erlangen, Germany.

29. Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.

Abstract

Background. Preformed donor-specific HLA antibodies (DSA) are a well-known risk factor in kidney transplantation. There is still considerable debate, however, about the optimal risk stratification among patients with preformed DSA. Additionally, data on the prognostic value of different crossmatch assays in DSA-positive patients are scarce. Methods. DSA-positive living kidney transplant recipients were selected from a multicenter study examining 4233 consecutive renal transplants. An additional 7 patients from 2 further centers were included. Flow cytometric crossmatches (FXM), Luminex-based crossmatches, and virtual crossmatches based on C1q- and C3d-binding antibodies (C1qXM and C3dXM) were performed retrospectively using pretransplant sera and lymphocytes isolated from fresh samples. These samples were obtained from 44 donor and recipient pairs from 12 centers. Clinical outcome data and the control group without DSA were compiled from the previous study and were supplemented by data on 10-y death-censored graft survival (10yGS). Results. Between 19% (C3dXM) and 46% (FXM) of crossmatches were positive. Crossmatch-positive patients showed high incidences of antibody-mediated rejection (AMR) within 6 mo (up to 60% in B-cell FXM+ patients). The incidence of AMR in crossmatch-negative patients ranged between 5% (FXM−) and 13% (C1qXM−). 10yGS was significantly impaired in patients with positive T-cell FXM and total FXM compared with both patients without DSA and those with DSA with negative FXM. Conclusions. Especially FXM are useful for risk stratification, as the outcome of DSA-positive, FXM-negative patients is similar to that of DSA-negative patients, whereas FXM-positive patients have both more AMR and decreased 10yGS. Because of their lower sensitivity, the significance of Luminex-based crossmatches, C1qXM, and C3dXM would have to be examined in patients with stronger DSA.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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