Introduction to Kidney Transplantation in sensitized patients

  • Duck Jong HanEmail author


Renal transplantation is widely accepted as the best therapeutic treatment modality for the patients with end stage renal disease. However sensitization to previous antigen exposure still remains one of the major clinical hurdles for successful kidney transplantation. In this book pre op evaluation for sensitized patients, pre op desensitization, post-transplant management, post-operative complications, and finally results are reviewed with our own data. As an introduction, this chapter deals with definition of sensitization, brief illustration of donor specific antibody(HLA and non HLA antibody), prevalence and cause of sensitization, and approach to the highly sensitized patients such as modification of deceased organ allocation system, acceptable mismatch program, and kidney paired exchange in addition to desensitization.


Sensitization Desensitization Organ allocation Acceptable mismatch Kidney paired exchange 


  1. 1.
    Wolfe RA, Ashby VB, Milford EL, 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(23):1725–30.PubMedCrossRefGoogle Scholar
  2. 2.
    McDonald SP, Russ GR. Survival of recipients of cadaveric kidney transplants compared with those receiving dialysis treatment in Australia and New Zealand, 1991–2001. Nephrol Dial Transplant. 2002;17(12):2212–9.CrossRefGoogle Scholar
  3. 3.
    Wyld M, Morton RL, Hayen A, et al. A systematic review and meta-analysis of utility-based quality of life in chronic kidney disease treatments. PLoS Med. 2012;9(9):e1001307.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Tonelli M, Wiebe N, Knoll G, et al. Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes. Am J Transplant. 2011;11(10):2093–109.PubMedCrossRefGoogle Scholar
  5. 5.
    Howard K, Salkeld G, White S, et al. The cost-effectiveness of increasing kidney transplantation and home-based dialysis. Nephrology (Carlton). 2009;14(1):123–32.CrossRefGoogle Scholar
  6. 6.
    Wong G, Howard K, Chapman JR, et al. Comparative survival and economic benefits of deceased donor kidney transplantation and dialysis in people with varying ages and co-morbidities. PLoS One. 2012;7(1):e29591.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Clayton PA, Coates PT. Are sensitized patients better off with a desensitization transplant or waiting on dialysis? Kidney Int. 2017;91(6):1266–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Reynolds BC, Tinckam KJ. Sensitization assessment before kidney transplantation. Transplant Rev (Orlando). 2017;31(1):18–28.CrossRefGoogle Scholar
  9. 9.
    Lim WH, Chapman JR, Wong G. Peak panel reactive antibody, cancer, graft, and patient outcomes in kidney transplant recipients. Transplantation. 2015;99(5):1043–50.PubMedCrossRefGoogle Scholar
  10. 10.
    Huber L, Lachmann N, Dürr M, et al. Identification and therapeutic management of highly sensitized patients undergoing renal transplantation. Drugs. 2012;72(10):1335–54.PubMedCrossRefGoogle Scholar
  11. 11.
    Pham TA, Lee JI, Melcher ML. Kidney paired exchange and desensitization: Strategies to transplant the difficult to match kidney patients with living donors. Transplant Rev (Orlando). 2017;31(1):29–34.CrossRefGoogle Scholar
  12. 12.
    Valenzuela NM, Reed EF. Antibodies in transplantation: The effects of HLA and non-HLA antibody binding and mechanisms of injury. Methods Mol Biol. 2013;1034:41–70.PubMedCrossRefGoogle Scholar
  13. 13.
    Kosmoliaptsis V, Sharples LD, Chaudhry AN, et al. Predicting HLA class II alloantigen immunogenicity from the number and physiochemical properties of amino acid polymorphisms. Transplantation. 2011;91:183–90.PubMedCrossRefGoogle Scholar
  14. 14.
    Loupy A, Vernerey D, Tinel C, et al. Subclinical rejection phenotypes at 1 year post-transplant and outcome of kidney allografts. J Am Soc Nephrol. 2015;26:1721–31.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Kumbala D, Zhang R. Essential concept of transplant immunology for clinical practice. World J Transplant. 2013;3(4):113–8.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    van den Berg-Loonen EM, EVA B, CEM V, et al. Clinical relevance of pretransplant donor-directed antibodies detected by single antigen beads in highly sensitized renal transplant patients. Transplantation. 2008;85:1086–90.PubMedCrossRefGoogle Scholar
  17. 17.
    Wehmeier C, Hönger G, Cun H, et al. Donor Specificity but Not Broadness of Sensitization Is Associated With Antibody-Mediated Rejection and Graft Loss in Renal Allograft Recipients. Am J Transplant. 2017;17(8):2092–102.PubMedCrossRefGoogle Scholar
  18. 18.
    Gupta A, Murillo D, Yarlagadda SG, et al. Donor-specific antibodies present at the time of kidney transplantation in immunologically unmodified patients increase the risk of acute rejection. Transpl Immunol. 2016;37:18–22.PubMedCrossRefGoogle Scholar
  19. 19.
    Hill B. Proceedings of the meeting. J R Stat Soc. 1956. Published 1956
  20. 20.
    Lonze BE. Histocompatibility and management of the highly sensitized kidney transplant candidate. Curr Opin Organ Transplant. 2017;22(4):415–20.PubMedCrossRefGoogle Scholar
  21. 21.
    Bartel G, Wahrmann M, Exner M, et al. Determinants of the complement-fixing ability of recipient presensitization against HLA antigens. Transplantation. 2007;83(6):727–33.PubMedCrossRefGoogle Scholar
  22. 22.
    Narayan S, Tsai EW, Zhang Q, et al. Pediatr Transplant. 2011;15(1):E1–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Terasaki PI, Ozawa M, Castro R. Four year follow up of a prospective trial of HLA and MICA antibodies on kidney graft survival. Am J Transplant. 2007;7(2):408–15.PubMedCrossRefGoogle Scholar
  24. 24.
    Lunz J, Hinsdale L, King C, et al. The coordination of allocation: Logistics of kidney organ allocation to highly sensitized patients. Hum Immunol. 2017;78(1):16–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Kumar V. Current status on the evaluation and management of the highly sensitized kidney transplant recipient. Curr Opin Nephrol Hypertens. 2015;24(6):570–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Tambur AR, Claas FH. HLA epitopes as viewed by antibodies: what is it all about? Am J Transplant. 2015;15(5):1148–54.PubMedCrossRefGoogle Scholar
  27. 27.
    Claas FH, Rahmel A, Doxiadis II. Enhanced kidney allocation to highly sensitized patients by the acceptable mismatch program. Transplantation. 2009;88(4):447–52.PubMedCrossRefGoogle Scholar
  28. 28.
    Keith DS, Vranic GM. Approach to the highly sensitized kidney transplant candidate. Clin J Am Soc Nephrol. 2016;11(4):684–93.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Duquesnoy RJ. Antibody-reactive epitope determination with HLAMatchmaker and its clinical applications. Tissue Antigens. 2011;77(6):525–34.PubMedCrossRefGoogle Scholar
  30. 30.
    Network OPTN. Scientific registry of transplant recipients. 2016.Google Scholar
  31. 31.
    Sethi S, Choi J, Toyoda M, et al. Desensitization: overcoming the immunologic barriers to transplantation. J Immunol Res. 2017;2017:6804678.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Marfo K, Lu A, Ling M, Akalin E. Desensitization protocol and their outcome. Clin J Am Soc Nephrol. 2011;6(4):922–36.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Lawrence C, Willicombe M, Brookes PA, et al. Preformed complement-activating low-level donor-specific antibody predicts early antibody-mediated rejection in renal allografts. Transplantation. 2013;95:341–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Filippone EJ, Farber JL. Humoral immune response and allograft function in kidney transplantation. Am J Kidney Dis. 2015;66:337–47.PubMedCrossRefGoogle Scholar
  35. 35.
    Bromberger B, Spragan D, Hashmi S, et al. Pregnancy-induced sensitization promotes sex disparity in living donor kidney transplantation. J Am Soc Nephrol. 2017;28(10):3025–33.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Brakemeier S, Schweiger B, Lachmann N, et al. Immune response to an adjuvanted influenza A H1N1 vaccine (Pandemrix(®)) in renal transplant recipients. Nephrol Dial Transplant. 2012;27(1):423–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Katerinis I, Hadaya K, Duquesnoy R, et al. De novo anti-HLA antibody after pandemic H1N1 and seasonal influenza immunization in kidney transplant recipients. Am J Transplant. 2011;11(8):1727–33.PubMedCrossRefGoogle Scholar
  38. 38.
    Tinckam KJ, Rose C, Hariharan S, Gill J. Re-examining risk of repeated HLA mismatch in kidney transplantation. J Am Soc Nephrol. 2016;27:2833–41.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Matignon M, Leibler C, Moranne O, et al. Anti-HLA sensitization after kidney allograft nephrectomy: changes one year post-surgery and beneficial effect of intravenous immunoglobulin. Clin Transpl. 2016;30(6):731–40.CrossRefGoogle Scholar
  40. 40.
    Del Bello A, Congy N, Sallusto F, et al. Anti-human leukocyte antigen immunization after early allograft nephrectomy. Transplantation. 2012;93(9):936–41.PubMedCrossRefGoogle Scholar
  41. 41.
    Tran TH, Dohler B, Heinold A, et al. Deleterious impact of mismatching for human leukocyte antigen-C in presensitized recipients of kidney transplants. Transplantation. 2011;92(4):419–25.PubMedCrossRefGoogle Scholar
  42. 42.
    Marrari M, Duquesnoy RJ. Detection of donor-specific HLA antibodies before and after removal of a rejected kidney transplant. Transpl Immunol. 2010;22(3–4):105–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Budde K, Dürr M. About incidence and timing of donor-specific antibodies after graft nephrectomy. Transplantation. 2012;93(9):865–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Redfield RR, Scalea JR, Zens TJ, et al. The mode of sensitization and its influence on allograft outcomes in highly sensitized kidney transplant recipients. Nephrol Dial Transplant. 2016;31(10):1746–53.PubMedCrossRefGoogle Scholar
  45. 45.
    Israni AK, Salkowski N, Gustafson S, et al. New national allocation policy for deceased donor kidneys in the United States and possible effect on patient outcomes. J Am Soc Nephrol. 2014;25:1842–8.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Nahin P. Digital dice: computational Solutions to Practical Probability Problems. Princeton, NJ: Princeton University Press; 2008. p. 30.Google Scholar
  47. 47.
    Dello Strologo L, Murer L, Guzzo I, et al. Renal transplantation in sensitized children and young adults: a nationwide approach. Nephrol Dial Transplant. 2017;32(1):191–5.Google Scholar
  48. 48.
    Heidt S, Witvliet MD, Haasnoot GW, Claas FH. The 25th anniversary of the Eurotransplant Acceptable Mismatch program for highly sensitized patients. Transpl Immunol. 2015;33(2):51–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Morath C, Opelz G, Zeier M, Süsal C. Recent developments in desensitization of crossmatch-positive kidney transplant recipients. Transplant Proc. 2012;44(6):1648–51.PubMedCrossRefGoogle Scholar
  50. 50.
    Inui M, Miyazato T, Furusawa M, et al. Successful kidney transplantation after stepwise desensitization using rituximab and bortezomib in a highly HLA-sensitized and ABO incompatible high titer patient. Transplant Direct. 2016;2(8):e92.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Marfo K, Lu A, Ling M, Akalin E. Desensitization protocols and their outcome. Clin J Am Soc Nephrol. 2011;6(4):922–36.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Montgomery RA, Lonze BE, King KE, et al. Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med. 2011;365(4):318–26.PubMedCrossRefGoogle Scholar
  53. 53.
    Orandi BJ, Luo X, Massie AB, et al. Survival benefit with kidney transplants from HLA-incompatible live donors. N Engl J Med. 2016;374(10):940–50.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Kahwaji J, Jordan SC, Najjar R, et al. Six-year outcomes in broadly HLA-sensitized living donor transplant recipients desensitized with intravenous immunoglobulin and rituximab. Transpl Int. 2016;29(12):1276–85.PubMedCrossRefGoogle Scholar
  55. 55.
    Abu Jawdeh BG, Cuffy MC, Alloway RR, et al. Desensitization in kidney transplantation: review and future perspectives. Clin Transpl. 2014;28(4):494–507.CrossRefGoogle Scholar
  56. 56.
    Manook M, Koeser L, Ahmed Z, et al. Post-listing survival for highly sensitised patients on the UK kidney transplant waiting list: a matched cohort analysis. Lancet. 2017;389(10070):727–34.PubMedCrossRefGoogle Scholar
  57. 57.
    Montgomery RA, Lonze BE, Jackson AM. Using donor exchange paradigms with desensitization to enhance transplant rates among highly sensitized patients. Curr Opin Organ Transplant. 2011;16(4):439–43.PubMedCrossRefGoogle Scholar
  58. 58.
    Jordan SC, Choi J, Vo A. Kidney transplantation in highly sensitized patients. Br Med Bull. 2015;114:113–25.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of General SurgeryAsan Medical CenterSeoulSouth Korea

Personalised recommendations