Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


HLA matching and graft survival in kidney transplantation

INTRODUCTION

The evidence that antigens of the human leukocyte antigen (HLA) system provide the major barrier to acceptance of renal transplants was first obtained with living related donor transplants. Graft survival was superior in sibling pairs having both the same serologically defined HLA antigens and a nonreactive in vitro mixed lymphocyte proliferative response when compared with randomly matched cadaveric donors treated with the same immunosuppressive drugs, principally azathioprine and prednisone. (The mixed lymphocyte response [MLR] is an in vitro estimate of incompatibility in which the degree of proliferation of the recipient lymphocytes to donor lymphocytes is measured.) There was an intermediate level of graft survival in haploidentical parent-to-child or sibling-to-sibling transplants, in which one but not both of the haplotypes matched.

The most valuable databases now in existence are those representing pooling of information from a large number of collaborating centers. Although such pooled data may suffer from variations in protocols and undocumented selection factors, the power of univariate analyses becomes compelling when thousands of patients are included. These large databases include the United Network for Organ Sharing (UNOS), the Collaborative Transplant Study (CTS), Scientific Registry of Transplant Recipients (SRTR), the American Southeast Organ Procurement Foundation (SEOPF), the United Kingdom Transplant Service, Eurotransplant, the Australian New Zealand Data (ANZDATA), and others.

RELATIVE IMPORTANCE OF HLA-A,-B, AND -DR

The simple assumption that each mismatch for HLA antigens has equal weight has not been borne out. The initial Collaborative Transplant Study (CTS) analysis showed that the major impact comes from the DR and B antigens, with little additional effect from the A antigens [1,2]. The UK Transplant and Eurotransplant data are somewhat similar, with DR matching having a much greater effect than that of B or A [3,4]. Another study found that HLA-DR mismatches (and the number of rejection episodes) correlated with poor long-term survival [5]. Each antigen also appears to exert its effect at different times posttransplant, with the maximal effect of DR and B mismatching occurring within the first six months and two years posttransplant, respectively [6].

A related issue is whether specific HLA mismatch combinations are associated with decreased renal allograft survival [7,8]. A retrospective study addressed this issue by examining 2877 unrelated renal transplants with one mismatch of either HLA-A, -B, or -DR [7]. Seven unique combinations ("taboo" mismatches) of recipient HLA antigen and donor HLA antigen were associated with significant decreases in graft survival when compared with survival among transplant groups with either no mismatch or one indifferent mismatch. At five years, graft survival among the groups without a mismatch, with one indifferent mismatch, or with one taboo mismatch was 72, 69, and 50 percent, respectively. The mechanism by which "taboo" HLA mismatches may result in diminished allograft survival is unknown.

When trying to match a donor to a recipient, avoidance of mismatches is used in preference to matching of HLA antigens. This approach maximizes the number of patients offered well-matched grafts because the same antigen may be present twice. As an example, HLA-A2 is a common antigen, and homozygosity is frequent. Such a patient can receive a graft with no mismatches; however, he or she cannot be matched for six HLA antigens since only five are present.

           

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2014. | This topic last updated: Nov 2, 2012.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Opelz G. Correlation of HLA matching with kidney graft survival in patients with or without cyclosporine treatment. Transplantation 1985; 40:240.
  2. Opelz, G. Collaborative Transplant Study Newsletter 1988; number 3.
  3. Gilks WR, Bradley BA, Gore SM, Klouda PT. Substantial benefits of tissue matching in renal transplantation. Transplantation 1987; 43:669.
  4. Doxiadis II, de Fijter JW, Mallat MJ, et al. Simpler and equitable allocation of kidneys from postmortem donors primarily based on full HLA-DR compatibility. Transplantation 2007; 83:1207.
  5. Coupel S, Giral-Classe M, Karam G, et al. Ten-year survival of second kidney transplants: impact of immunologic factors and renal function at 12 months. Kidney Int 2003; 64:674.
  6. Dialysis and Transplantation, Owen WF, Pereira BJ, Sayegh MH (Eds), WB Saunders, Philadelphia 2000. p.504.
  7. Doxiadis II, Smits JM, Schreuder GM, et al. Association between specific HLA combinations and probability of kidney allograft loss: the taboo concept. Lancet 1996; 348:850.
  8. Reisaeter AV, Leivestad T, Vartdal F, et al. A strong impact of matching for a limited number of HLA-DR antigens on graft survival and rejection episodes: a single-center study of first cadaveric kidneys to nonsensitized recipients. Transplantation 1998; 66:523.
  9. Cecka JM, Terasaki PI. The UNOS Renal Transplant Registry. In: Clinical Transplants 1993, Terasaki PI, Cecka JM (Eds), UCLA Tissue Typing Laboratory, Los Angeles 1994. p.1.
  10. Takemoto SK, Terasaki PI, Gjertson DW, Cecka JM. Twelve years' experience with national sharing of HLA-matched cadaveric kidneys for transplantation. N Engl J Med 2000; 343:1078.
  11. The Scientific Registry of Transplant Recipients http://www.ustransplant.org (Accessed on February 02, 2010).
  12. Hariharan S, Johnson CP, Bresnahan BA, et al. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med 2000; 342:605.
  13. Meier-Kriesche HU, Ojo AO, Leichtman AB, et al. Interaction of mycophenolate mofetil and HLA matching on renal allograft survival. Transplantation 2001; 71:398.
  14. Andresdottir MB, Hoitsma AJ, Assmann KJ, et al. The impact of recurrent glomerulonephritis on graft survival in recipients of human histocompatibility leucocyte antigen-identical living related donor grafts. Transplantation 1999; 68:623.
  15. Lee CM, Carter JT, Alfrey EJ, et al. Prolonged cold ischemia time obviates the benefits of 0 HLA mismatches in renal transplantation. Arch Surg 2000; 135:1016.
  16. Schnitzler MA, Hollenbeak CS, Cohen DS, et al. The economic implications of HLA matching in cadaveric renal transplantation. N Engl J Med 1999; 341:1440.
  17. Su X, Zenios SA, Chakkera H, et al. Diminishing significance of HLA matching in kidney transplantation. Am J Transplant 2004; 4:1501.
  18. Opelz G, Döhler B. Effect of human leukocyte antigen compatibility on kidney graft survival: comparative analysis of two decades. Transplantation 2007; 84:137.
  19. http://www.ustransplant.org (Accessed on February 02, 2010).
  20. Meier-Kriesche HU, Scornik JC, Susskind B, et al. A lifetime versus a graft life approach redefines the importance of HLA matching in kidney transplant patients. Transplantation 2009; 88:23.
  21. Young CJ, Gaston RS. Renal transplantation in black Americans. N Engl J Med 2000; 343:1545.
  22. Roberts JP, Wolfe RA, Bragg-Gresham JL, et al. Effect of changing the priority for HLA matching on the rates and outcomes of kidney transplantation in minority groups. N Engl J Med 2004; 350:545.
  23. Mutinga N, Brennan DC, Schnitzler MA. Consequences of eliminating HLA-B in deceased donor kidney allocation to increase minority transplantation. Am J Transplant 2005; 5:1090.
  24. Bahram S, Bresnahan M, Geraghty DE, Spies T. A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci U S A 1994; 91:6259.
  25. Zwirner NW, Marcos CY, Mirbaha F, et al. Identification of MICA as a new polymorphic alloantigen recognized by antibodies in sera of organ transplant recipients. Hum Immunol 2000; 61:917.
  26. Zou Y, Heinemann FM, Grosse-Wilde H, et al. 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 2006; 67:230.
  27. Sumitran-Karuppan S, Tyden G, Reinholt F, et al. Hyperacute rejections of two consecutive renal allografts and early loss of the third transplant caused by non-HLA antibodies specific for endothelial cells. Transpl Immunol 1997; 5:321.
  28. Mizutani K, Terasaki P, Rosen A, et al. Serial ten-year follow-up of HLA and MICA antibody production prior to kidney graft failure. Am J Transplant 2005; 5:2265.
  29. 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; 7:408.
  30. Zou Y, Stastny P, Süsal C, et al. Antibodies against MICA antigens and kidney-transplant rejection. N Engl J Med 2007; 357:1293.
  31. Gratwohl A, Döhler B, Stern M, Opelz G. H-Y as a minor histocompatibility antigen in kidney transplantation: a retrospective cohort study. Lancet 2008; 372:49.
  32. Burlingham WJ, Grailer AP, Heisey DM, et al. The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors. N Engl J Med 1998; 339:1657.
  33. Sanfilippo F. Transplantation tolerance--the search continues. N Engl J Med 1998; 339:1700.