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The arduous road to achieving an immunosuppression-free state in kidney transplant recipients

Nature Clinical Practice Nephrology volume 3, pages 464–465 (2007)Cite this article

Transplantation has come a long way since the first successful procedures around half a century ago, with revolutionary advances having been made in immunosuppressive medications and remarkable improvements seen in early graft outcomes.1 Disappointingly, long-term outcomes remain unsatisfactory: there has been no improvement in long-term graft survival, and grafts are still lost predominantly because of chronic rejection and immunosuppressive drug toxicity.1 Furthermore, the increased risks of cardiovascular disease, hypertension, diabetes, hyperlipidemia, infections and malignancy associated with immunosuppressive therapy limit the long-term success of kidney transplantation. It seems reasonable, therefore, to work towards achieving a state of transplantation tolerance. As there is no precise assay for tolerance in humans, such a state is referred to as 'operational tolerance', indicating stable allograft function in the absence of immunosuppressive therapy in an immunocompetent recipient. The ability to achieve this state would improve transplant longevity and help alleviate the shortage of organs for transplantation. For these reasons, the burning desire of transplantation immunobiologists to be able to predictably induce durable tolerance has become more intense than ever.2,3

In the face of difficulties and repeated failures, the desire to achieve clinical tolerance is nurtured and maintained by rare but encouraging in human occurrences of the phenomenon. Tolerance has been noted in patients receiving total body lymphoid irradiation,4 patients who receive bone marrow transplants and a simultaneous5 or subsequent6 kidney transplant from the same donor, a minority of liver transplant recipients whose immunosuppression is withdrawn intentionally,7 and an even smaller minority of noncompliant patients who have discontinued their immunosuppression.8 These examples illustrate the two differing approaches to induction of tolerance—a radical de novo induction protocol combined with rapid withdrawal of immunosuppression, or gradual withdrawal of immunosuppression in selected recipients—and they fuel the ongoing debate as to which strategy will ultimately allow successful complete withdrawal of immunosuppression.

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References

  1. Sayegh MH and Carpenter CB (2004) Transplantation 50 years later—progress, challenges, and promises. N Engl J Med 351: 2761–2766

    Article  CAS  Google Scholar 

  2. Salama AD et al. (2001) Challenges to achieving clinical transplantation tolerance. J Clin Invest 108: 943–948

    Article  CAS  Google Scholar 

  3. Matthews JB et al. (2003) Clinical trials of transplant tolerance: slow but steady progress. Am J Transplant 3: 794–803

    Article  Google Scholar 

  4. Strober S et al. (1989) Acquired immune tolerance to cadaveric renal allografts: a study of three patients treated with total lymphoid irradiation. N Engl J Med 321: 28–33

    Article  CAS  Google Scholar 

  5. Fudaba Y et al. (2006) Myeloma responses and tolerance following combined kidney and nonmyeloablative marrow transplantation: in vivo and in vitro analyses. Am J Transplant 6: 2121–2133

    Article  CAS  Google Scholar 

  6. Sayegh MH et al. (1991) Immunologic tolerance to renal allografts after bone marrow transplants from the same donors. Ann Intern Med 114: 954–955

    Article  CAS  Google Scholar 

  7. Martinez-Llordella M et al. (2007) Multiparameter immune profiling of operational tolerance in liver transplantation. Am J Transplant 7: 309–319

    Article  CAS  Google Scholar 

  8. Roussey-Kesler G et al. (2006) Clinical operational tolerance after kidney transplantation. Am J Transplant 6: 736–746

    Article  CAS  Google Scholar 

  9. Calne R et al. (1999) Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients. Transplantation 68: 1613–1616

    Article  CAS  Google Scholar 

  10. Kirk AD et al. (2003) Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation 76: 120–129

    Article  CAS  Google Scholar 

  11. Barth RN et al. (2006) Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation. Transpl Int 19: 885–892

    Article  CAS  Google Scholar 

  12. Swanson SJ et al. (2002) Kidney transplantation with rabbit antithymocyte globulin induction and sirolimus monotherapy. Lancet 360: 1662–1664

    Article  CAS  Google Scholar 

  13. Starzl TE et al. (2003) Tolerogenic immunosuppression for organ transplantation. Lancet 361: 1502–1510

    Article  Google Scholar 

  14. Denton MD et al. (1999) Immunosuppressive strategies in transplantation. Lancet 353: 1083–1091

    Article  CAS  Google Scholar 

  15. Neujahr DC et al. (2006) Accelerated memory cell homeostasis during T cell depletion and approaches to overcome it. J Immunol 176: 4632–4639

    Article  CAS  Google Scholar 

  16. Sayegh MH and Remuzzi G (2007) Clinical update: immunosuppression minimisation. Lancet 369: 1676–1678

    Article  Google Scholar 

  17. Najafian N et al. (2006) How can we measure immunologic tolerance in humans? J Am Soc Nephrol 17: 2652–2663

    Article  CAS  Google Scholar 

  18. Chen L et al. (2006) TLR engagement prevents transplantation tolerance. Am J Transplant 6: 2282–2291

    Article  CAS  Google Scholar 

  19. Adams AB et al. (2003) Heterologous immunity provides a potent barrier to transplantation tolerance. J Clin Invest 111: 1887–1895

    Article  CAS  Google Scholar 

  20. Cai J et al. (2004) Correlation between human leukocyte antigen antibody production and serum creatinine in patients receiving sirolimus monotherapy after Campath-1H induction. Transplantation 78: 919–924

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Renal Division, Renal Division, MJ Ansari is a Staff Transplant Nephrologist in the Transplantation Research Center, Brigham and Women's Hospital, and an Instructor in Medicine at Harvard Medical School, and MH Sayegh is the Warren E Grupe and John P Merrill Chair in Transplantation Medicine and Professor of Medicine and Pediatrics at Harvard Medical School, and Director of the Transplantation Research Center, Brigham and Women's Hospital, Boston, MA, USA.,

    M Javeed Ansari & Mohamed H Sayegh

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  1. M Javeed Ansari
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  2. Mohamed H Sayegh
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Correspondence to Mohamed H Sayegh.

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Ansari, M., Sayegh, M. The arduous road to achieving an immunosuppression-free state in kidney transplant recipients. Nat Rev Nephrol 3, 464–465 (2007). https://doi.org/10.1038/ncpneph0568

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