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Kidney transplantation in highly sensitized patients: are there options to overcome a positive crossmatch?

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Abstract

Presensitization against a broad array of human leukocyte antigens (HLA) is associated with prolonged waiting times and inferior graft survival in kidney transplantation. Since the late 1960s, a positive lymphocytotoxic crossmatch has been considered a contraindication for kidney transplantation and solutions, such as enrollment of eligible patients in the Acceptable Mismatch Program of Eurotransplant and kidney paired donation in the case of living donor kidney transplantation, have been proposed to avoid this barrier. Alternatively, a positive crossmatch might not be considered as a contraindication for kidney transplantation and one can try to overcome this hurdle by desensitization. In principle, there are three different ways to overcome the crossmatch barrier by desensitization. The highly sensitized patient awaiting a cadaveric kidney transplant may be desensitized either immediately pretransplant when an organ is offered or in advance, during the time on the waiting list, to increase his chance of having a negative crossmatch at the time of transplantation. In the case of living donor kidney transplantation, the patient can be desensitized for days to weeks until the positive crossmatch with his intended living kidney donor becomes negative. “Heidelberg algorithm” is a combination of different measures, such as pretransplant risk estimation, good HLA match, inclusion of patients in the Eurotransplant Acceptable Mismatch program, and desensitization, which leads to timely transplantation and excellent survival rates in highly sensitized patients at a low rate of toxicity. We believe that all available options should be utilized in an integrated manner for the transplantation of kidney transplant recipients who are at a high risk of antibody-mediated rejection.

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References

  1. El-Awar N, Terasaki P, Lazda V, Nikaein A, Manning C, Arnold AN (2002) Almost all patients who are waiting for a regraft of a kidney transplant have anti-HLA antibodies. Transplant Proc 34:2531–2532

    Article  PubMed  CAS  Google Scholar 

  2. Opelz G (2005) Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies. Lancet 365:1570–1576

    Article  PubMed  CAS  Google Scholar 

  3. Zou Y, Heinemann FM, Grosse-Wilde H, Sireci G, Wang Z, Lavingia B, Stastny P (2006) Detection of anti-MICA antibodies in patients awaiting kidney transplantation, during the post-transplant course, and in eluates from rejected kidney allografts by Luminex flow cytometry. Hum Immunol 67:230–237

    Article  PubMed  CAS  Google Scholar 

  4. Reinsmoen NL, Lai CH, Heidecke H, Haas M, Cao K, Ong G, Naim M, Wang Q, Mirocha J, Kahwaji J, Vo AA, Jordan SC, Dragun D (2010) Anti-angiotensin type 1 receptor antibodies associated with antibody mediated rejection in donor HLA antibody negative patients. Transplantation 90:1473–1477

    Article  PubMed  CAS  Google Scholar 

  5. Breimer ME, Rydberg L, Jackson AM, Lucas DP, Zachary AA, Melancon JK, Von Visger J, Pelletier R, Saidman SL, Williams WW Jr, Holgersson J, Tyden G, Klintmalm GK, Coultroup S, Sumitran-Holgersson S, Grufman P (2009) Multicenter evaluation of a novel endothelial cell crossmatch test in kidney transplantation. Transplantation 87:549–556

    Article  PubMed  CAS  Google Scholar 

  6. Fuggle SV, Martin S (2008) Tools for human leukocyte antigen antibody detection and their application to transplanting sensitized patients. Transplantation 86:384–390

    Article  PubMed  CAS  Google Scholar 

  7. Süsal C, Döhler B, Opelz G (2009) Presensitized kidney graft recipients with HLA class I and II antibodies are at increased risk for graft failure: a collaborative transplant study report. Hum Immunol 70:569–573

    Article  PubMed  Google Scholar 

  8. Collaborative Transplant Study, University of Heidelberg, Germany, Website. Available from: www.ctstransplant.org. Accessed on 25 January 2011.

  9. Claas FH, Witvliet MD, Duquesnoy RJ, Persijn GG, Doxiadis II (2004) The acceptable mismatch program as a fast tool for highly sensitized patients awaiting a cadaveric kidney transplantation: short waiting time and excellent graft outcome. Transplantation 78:190–193

    Article  PubMed  Google Scholar 

  10. Doxiadis II, Smits JM, Persijn GG, Frei U, Claas FH (2004) It takes six to boogie: allocating cadaver kidneys in Eurotransplant. Transplantation 77:615–617

    Article  PubMed  Google Scholar 

  11. Claas FH, Rahmel A, Doxiadis II (2009) Enhanced kidney allocation to highly sensitized patients by the acceptable mismatch program. Transplantation 88:447–452

    Article  PubMed  Google Scholar 

  12. Morath C, Beimler J, Opelz G, Ovens J, Scherer S, Schmidt J, Schmied B, Gross ML, Schwenger V, Zeier M, Süsal C (2010) An integrative approach for the transplantation of high-risk sensitized patients. Transplantation 90:645–653

    Article  PubMed  Google Scholar 

  13. Beimler JH, Morath C, Schmidt J, Ovens J, Opelz G, Rahmel A, Zeier M, Süsal C (2009) Successful deceased-donor kidney transplantation in crossmatch-positive patients with peritransplant plasma exchange and Rituximab. Transplantation 87:668–671

    Article  PubMed  CAS  Google Scholar 

  14. Bartel G, Wahrmann M, Regele H, Kikic Z, Fischer G, Druml W, Muhlbacher F, Bohmig GA (2010) Peritransplant immunoadsorption for positive crossmatch deceased donor kidney transplantation. Am J Transplant 10:2033–2042

    Article  PubMed  CAS  Google Scholar 

  15. Glotz D, Antoine C, Julia P, Suberbielle-Boissel C, Boudjeltia S, Fraoui R, Hacen C, Duboust A, Bariety J (2002) Desensitization and subsequent kidney transplantation of patients using intravenous immunoglobulins (IVIg). Am J Transplant 2:758–760

    Article  PubMed  CAS  Google Scholar 

  16. Jordan SC, Tyan D, Stablein D, McIntosh M, Rose S, Vo A, Toyoda M, Davis C, Shapiro R, Adey D, Milliner D, Graff R, Steiner R, Ciancio G, Sahney S, Light J (2004) Evaluation of intravenous immunoglobulin as an agent to lower allosensitization and improve transplantation in highly sensitized adult patients with end-stage renal disease: report of the NIH IG02 trial. J Am Soc Nephrol 15:3256–3262

    Article  PubMed  Google Scholar 

  17. Montgomery RA, Zachary AA, Racusen LC, Leffell MS, King KE, Burdick J, Maley WR, Ratner LE (2000) Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into crossmatch-positive recipients. Transplantation 70:887–895

    Article  PubMed  CAS  Google Scholar 

  18. Zachary AA, Montgomery RA, Ratner LE, Samaniego-Picota M, Haas M, Kopchaliiska D, Leffell MS (2003) Specific and durable elimination of antibody to donor HLA antigens in renal transplant patients. Transplantation 76:1519–1525

    Article  PubMed  CAS  Google Scholar 

  19. Stegall MD, Gloor J, Winters JL, Moore SB, Degoey S (2006) A comparison of plasmapheresis versus high-dose IVIG desensitization in renal allograft recipients with high levels of donor specific alloantibody. Am J Transplant 6:346–351

    Article  PubMed  CAS  Google Scholar 

  20. Everly MJ, Everly JJ, Susskind B, Brailey P, Arend LJ, Alloway RR, Roy-Chaudhury P, Govil A, Mogilishetty G, Rike AH, Cardi M, Wadih G, Tevar A, Woodle ES (2008) Bortezomib provides effective therapy for antibody- and cell-mediated acute rejection. Transplantation 86:1754–1761

    Article  PubMed  CAS  Google Scholar 

  21. Perry DK, Burns JM, Pollinger HS, Amiot BP, Gloor JM, Gores GJ, Stegall MD (2009) Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production. Am J Transplant 9:201–209

    Article  PubMed  CAS  Google Scholar 

  22. Stegall M, Tayyab D, Lynn C, Justin B, Patrick D, Gloor J (2010) Terminal complement inhibition decreases early acute humoral rejection in sensitized renal transplant recipients. Am J Transplant 10:39

    Article  Google Scholar 

  23. Higgins RM, Bevan DJ, Carey BS, Lea CK, Fallon M, Buhler R, Vaughan RW, O’Donnell PJ, Snowden SA, Bewick M, Hendry BM (1996) Prevention of hyperacute rejection by removal of antibodies to HLA immediately before renal transplantation. Lancet 348:1208–1211

    Article  PubMed  CAS  Google Scholar 

  24. Haas M, Bohmig GA, Leko-Mohr Z, Exner M, Regele H, Derfler K, Horl WH, Druml W (2002) Peri-operative immunoadsorption in sensitized renal transplant recipients. Nephrol Dial Transplant 17:1503–1508

    Article  PubMed  Google Scholar 

  25. Lorenz M, Regele H, Schillinger M, Kletzmayr J, Haidbauer B, Derfler K, Druml W, Bohmig GA (2005) Peritransplant immunoadsorption: a strategy enabling transplantation in highly sensitized crossmatch-positive cadaveric kidney allograft recipients. Transplantation 79:696–701

    Article  PubMed  Google Scholar 

  26. Watanabe J, Scornik JC (2005) IVIG and HLA antibodies. Evidence for inhibition of complement activation but not for anti-idiotypic activity. Am J Transplant 5:2786–2790

    Article  PubMed  CAS  Google Scholar 

  27. Vo AA, Lukovsky M, Toyoda M, Wang J, Reinsmoen NL, Lai CH, Peng A, Villicana R, Jordan SC (2008) Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med 359:242–251

    Article  PubMed  CAS  Google Scholar 

  28. Patel R, Terasaki PI (1969) Significance of the positive crossmatch test in kidney transplantation. N Engl J Med 280:735–739

    Article  PubMed  CAS  Google Scholar 

  29. Süsal C, Opelz G (2002) Kidney graft failure and presensitization against HLA class I and class II antigens. Transplantation 73:1269–1273

    Article  PubMed  Google Scholar 

  30. Süsal C, Ovens J, Mahmoud K (2011) No association of kidney graft loss with HLA antibodies detected exclusively by sensitive Luminex single antigen testing .Transplantation (in press)

  31. Gupta A, Iveson V, Varagunam M, Bodger S, Sinnott P, Thuraisingham RC (2008) Pretransplant donor-specific antibodies in cytotoxic negative crossmatch kidney transplants: are they relevant? Transplantation 85:1200–1204

    Article  PubMed  CAS  Google Scholar 

  32. van den Berg-Loonen EM, Billen EV, Voorter CE, van Heurn LW, Claas FH, van Hooff JP, Christiaans MH (2008) Clinical relevance of pretransplant donor-directed antibodies detected by single antigen beads in highly sensitized renal transplant patients. Transplantation 85:1086–1090

    Article  PubMed  Google Scholar 

  33. Qiu J, Cai J, Terasaki PI, El-Awar N, Lee JH (2005) Detection of antibodies to HLA-DP in renal transplant recipients using single antigen beads. Transplantation 80:1511–1513

    Article  PubMed  CAS  Google Scholar 

  34. Kinukawa T, Kato M, Terasaki PI, Ozawa M (2006) Retrospective antibody analysis of thirty patients with kidney graft failure. Clin Transpl 291–303

  35. Dittrich E, Schmaldienst S, Derfler K (2007) Plasma exchange and immunoadsorption. Wien Klin Wochenschr 119:39–53, quiz 54

    PubMed  Google Scholar 

  36. Yeh JH, Chiu HC (2000) Comparison between double-filtration plasmapheresis and immunoadsorption plasmapheresis in the treatment of patients with myasthenia gravis. J Neurol 247:510–513

    Article  PubMed  CAS  Google Scholar 

  37. Terasaki PI (2003) Humoral theory of transplantation. Am J Transplant 3:665–673

    Article  PubMed  Google Scholar 

  38. Einecke G, Sis B, Reeve J, Mengel M, Campbell PM, Hidalgo LG, Kaplan B, Halloran PF (2009) Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transplant 9:2520–2531

    Article  PubMed  CAS  Google Scholar 

  39. Meier-Kriesche HU, Scornik JC, Susskind B, Rehman S, Schold JD (2009) A lifetime versus a graft life approach redefines the importance of HLA matching in kidney transplant patients. Transplantation 88:23–29

    Article  PubMed  Google Scholar 

  40. Thielke JJ, West-Thielke PM, Herren HL, Bareato U, Ommert T, Vidanovic V, Campbell-Lee SA, Tzvetanov IG, Sankary HN, Kaplan B, Benedetti E, Oberholzer J (2009) Living donor kidney transplantation across positive crossmatch: the University of Illinois at Chicago experience. Transplantation 87:268–273

    Article  PubMed  Google Scholar 

  41. Haririan A, Nogueira J, Kukuruga D, Schweitzer E, Hess J, Gurk-Turner C, Jacobs S, Drachenberg C, Bartlett S, Cooper M (2009) Positive cross-match living donor kidney transplantation: longer-term outcomes. Am J Transplant 9:536–542

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology, University of Heidelberg, Im Neuenheimer Feld 162, 69120, Heidelberg, Germany

    Christian Morath & Martin Zeier

  2. Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

    Jan Schmidt

  3. Transplantation Immunology, University of Heidelberg, Heidelberg, Germany

    Gerhard Opelz & Caner Süsal

Authors
  1. Christian Morath
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  2. Jan Schmidt
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  3. Gerhard Opelz
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  4. Martin Zeier
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  5. Caner Süsal
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Correspondence to Christian Morath.

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Morath, C., Schmidt, J., Opelz, G. et al. Kidney transplantation in highly sensitized patients: are there options to overcome a positive crossmatch?. Langenbecks Arch Surg 396, 467–474 (2011). https://doi.org/10.1007/s00423-011-0759-x

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  • DOI: https://doi.org/10.1007/s00423-011-0759-x

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