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Incompatible kidney transplantation: lessons from a decade of desensitization and paired kidney exchange

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Abstract

Human leukocyte antigen (HLA) sensitization and ABO incompatibility continue to pose significant barriers to further expansion of live donor renal transplantation. However, the recent development of effective desensitization protocols and creative paired donation strategies demonstrates that the presence of circulating donor HLA-specific antibodies and the use of ABO incompatible organs should no longer be considered contraindications for renal transplantation. It is estimated that as many as 6,000 patients on the kidney transplant waiting list have incompatible living donors and could benefit from these treatments. Furthermore, as our understanding of these treatment modalities has improved, it is now possible to predict whether desensitization, kidney paired donation or a combination of both will provide an individual patient with their best chance for successful renal transplantation.

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References

  1. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341:1725–30.

    Article  CAS  PubMed  Google Scholar 

  2. Ratner LE, Ciseck LJ, Moore RG, Cigarroa FG, Kaufman HS, Kavoussi LR. Laparoscopic live donor nephrectomy. Transplantation. 1995;60:1047–9.

    CAS  PubMed  Google Scholar 

  3. Ratner LE, Kavoussi LR, Sroka M, Hiller J, Weber R, Schulam PG, et al. Laparoscopic assisted live donor nephrectomy–a comparison with the open approach. Transplantation. 1997;63:229–33.

    Article  CAS  PubMed  Google Scholar 

  4. Ratner LE, Montgomery RA, Maley WR, Cohen C, Burdick J, Chavin KD, et al. Laparoscopic live donor nephrectomy: the recipient. Transplantation. 2000;69:2319–23.

    Article  CAS  PubMed  Google Scholar 

  5. Kissmeyer-Nielsen F, Olsen S, Petersen VP, Fjeldborg O. Hyperacute rejection of kidney allografts, associated with pre-existing humoral antibodies against donor cells. Lancet. 1966;2:662–5.

    Article  CAS  PubMed  Google Scholar 

  6. Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med. 1969;280:735–9.

    CAS  PubMed  Google Scholar 

  7. Rydberg L. ABO-incompatibility in solid organ transplantation. Transfus Med. 2001;11:325–42.

    Article  CAS  PubMed  Google Scholar 

  8. Williams GM, Hume DM, Hudson RP Jr, Morris PJ, Kano K, Milgrom F. “Hyperacute” renal-homograft rejection in man. N Engl J Med. 1968;279:611–8.

    Article  CAS  PubMed  Google Scholar 

  9. Segev DL, Gentry SE, Warren DS, Reeb B, Montgomery RA. Kidney paired donation and optimizing the use of live donor organs. JAMA. 2005;293:1883–90.

    Article  CAS  PubMed  Google Scholar 

  10. Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med. 2001;345:747–55.

    Article  CAS  PubMed  Google Scholar 

  11. Glotz D, Antoine C, Julia P, Pegaz-Fiornet B, Duboust A, Boudjeltia S, et al. Intravenous immunoglobulins and transplantation for patients with anti-HLA antibodies. Transpl Int. 2004;17:1–8.

    Article  CAS  PubMed  Google Scholar 

  12. Glotz D, Antoine C, Julia P, Suberbielle-Boissel C, Boudjeltia S, Fraoui R, et al. Desensitization and subsequent kidney transplantation of patients using intravenous immunoglobulins (IVIg). Am J Transplant. 2002;2:758–60.

    Article  CAS  PubMed  Google Scholar 

  13. Jordan S, Tyan D, Stablein D, Mcintosh M, Rose S, Vo A, et al. 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. 2004;15:3256–62.

    Article  PubMed  Google Scholar 

  14. Jordan SC, Vo A, Peng A, Toyoda M, Tyan D. Intravenous gammaglobulin (IVIG): a novel approach to improve transplant rates and outcomes in highly HLA-sensitized patients. Am J Transplant. 2006;6:459–66.

    Article  CAS  PubMed  Google Scholar 

  15. Montgomery RA, Zachary AA, Racusen LC, Leffell MS, King KE, Burdick J, et al. Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients. Transplantation. 2000;70:887–95.

    Article  CAS  PubMed  Google Scholar 

  16. Gloor JM, Lager DJ, Moore SB, Pineda AA, Fidler ME, Larson TS, et al. ABO-incompatible kidney transplantation using both A2 and non-A2 living donors. Transplantation. 2003;75:971–7.

    Article  CAS  PubMed  Google Scholar 

  17. Gloor JM, Lager D, Fidler M, Grande JP, Moore SB, Winters J, et al. A Comparison of splenectomy versus intensive posttransplant antidonor blood group antibody monitoring without splenectomy in ABO-incompatible kidney transplantation. Transplantation. 2005;80:1572–7.

    Article  PubMed  Google Scholar 

  18. Montgomery R, Locke J, King K, Segev D, Warren DS, Kraus E, et al. ABO incompatible renal transplantation: a paradigm ready for broad implementation. Transplantation. 2009;87:1246–55.

    Article  PubMed  Google Scholar 

  19. Segev DL, Simpkins C, Warren D, King K, Shirey R, Maley W, et al. ABO incompatible high-titer renal transplantation without splenectomy or anti-CD20 treatment. Am J Transplant. 2005;5:2570–5.

    Article  PubMed  Google Scholar 

  20. Sonnenday CJ, Warren DS, Cooper M, Samaniego M, Haas M, King KE, et al. Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy. Am J Transplant. 2004;4:1315–22.

    Article  CAS  PubMed  Google Scholar 

  21. Alexandre GP, Squifflet JP, De Bruyere M, Latinne D, Reding R, Gianello P, et al. Present experiences in a series of 26 ABO-incompatible living donor renal allografts. Transplant Proc. 1987;19:4538–42.

    CAS  PubMed  Google Scholar 

  22. Hume DM, Merill JP, Miller BF, Thorn DW. Experiences with renal allotransplantation in the human: report of nine cases. J Clin Invest. 1955;34:327–32.

    Article  CAS  PubMed  Google Scholar 

  23. Starzl TE, Machioro TL, Holmes JH, Hermann G, Brittain RS, Stonington OH, et al. Renal homograft’s in patients with major donor-recipient blood group incompatibilities. Surgery. 1964;55:195–200.

    CAS  PubMed  Google Scholar 

  24. Tanabe K, Takahashi K, Tokumoto T, Ishikawa N, Oshima T, Kanematsu A, et al. Infectious complications in ABO-incompatible living donor kidney transplantation: a single center experience. Transplant Proc. 1998;30:3130–2.

    Article  CAS  PubMed  Google Scholar 

  25. Alexandre GP, Squifflet JP, De Bruyere M, Latinne D, Moriau M, Ikabu N, et al. Splenectomy as a prerequisite for successful human ABO-incompatible renal-transplantation. Transplant Proc. 1985;17:138–43.

    Google Scholar 

  26. Locke J, Magro CM, Singer A, Segev D, Haas M, Hillel A, et al. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection. Am J Transplant. 2009;9:231–5.

    Article  CAS  PubMed  Google Scholar 

  27. Locke J, Zachary A, Haas M, Melancon J, Warren D, Simpkins C, et al. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection. Am J Transplant. 2007;7:842–6.

    Article  CAS  PubMed  Google Scholar 

  28. Everly M, Everly J, Susskind B, Brailey P, Arend L, Alloway R, et al. Bortezomib provides effective therapy for antibody- and cell-mediated acute rejection. Transplantation. 2008;86:1754–61.

    Article  CAS  PubMed  Google Scholar 

  29. Tyden G, Kumlien G, Genberg H, Sandberg J, Lundgren T, Fehrman I. ABO-incompatible kidney transplantation and rituximab. Transplant Proc. 2005;37:3286–7.

    Article  CAS  PubMed  Google Scholar 

  30. Terasaki P, Gjertson D, Cecka J. Paired kidney exchange is not a solution to ABO incompatibility. Transplantation. 1998;65:291.

    Article  CAS  PubMed  Google Scholar 

  31. Montgomery RA, Zachary AA, Ratner LE, Segev DL, Hiller JM, Houp J, et al. Clinical results from transplanting incompatible live kidney donor/recipient pairs using kidney paired donation. JAMA. 2005;294:1655–63.

    Article  CAS  PubMed  Google Scholar 

  32. Segev D, Kucirka LM, Gentry SE, Montgomery R. Utilization and outcomes of kidney paired donation in the United States. Transplantation. 2008;86:502–10.

    Article  PubMed  Google Scholar 

  33. Montgomery R, Gentry SE, Marks W, Warren D, Hiller J, Houp J, et al. Domino paired kidney donation: a strategy to make best use of live non-directed donation. Lancet. 2006;368:419–21.

    Article  PubMed  Google Scholar 

  34. Rees M, Kopke J, Pelletier R, Segev D, Rutter M, Fabrega AJ, et al. A nonsimultaneous, extended, altruistic-donor chain. N Engl J Med. 2009;360:1096–101.

    Article  CAS  PubMed  Google Scholar 

  35. Gentry SE, Montgomery R, Swihart B, Segev D. The roles of dominos and nonsimultaneous chains in kidney paired donation. Am J Transplant. 2009;9:1330–6.

    Article  CAS  PubMed  Google Scholar 

  36. Segev DL, Gentry SE, Melancon JK, Montgomery RA. Characterization of waiting times in a simulation of kidney paired donation. Am J Transplant. 2005;5:2448–55.

    Article  PubMed  Google Scholar 

  37. Gentry SE, Segev DL, Montgomery RA. A comparison of populations served by kidney paired donation and list paired donation. Am J Transplant. 2005;5:1914–21.

    Article  PubMed  Google Scholar 

  38. Warren DS, Zachary AA, Sonnenday CJ, King KE, Cooper M, Ratner LE, et al. Successful renal transplantation across simultaneous ABO incompatible and positive cross match barriers. Am J Transplant. 2004;4:561–8.

    Article  PubMed  Google Scholar 

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Correspondence to Robert A. Montgomery.

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Warren, D.S., Montgomery, R.A. Incompatible kidney transplantation: lessons from a decade of desensitization and paired kidney exchange. Immunol Res 47, 257–264 (2010). https://doi.org/10.1007/s12026-009-8157-y

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