Abstract
Immunosuppression is the mayor mechanism to prevent allograft rejection and to induce tolerance. Since the first solid organ transplant, the development of safe and effective immunosuppressive regimens was a constant over the last decades. A lot of immunosuppressants have been discovered, and today the immunosuppressive agents are classified in two broad groups: Xenobiotic immunosuppressants and biological immunosuppressants. Xenobiotics, like corticoids and calcineurin and mTOR inhibitors, mainly interfere with the intracellular molecular mechanisms of the various types of cells involved in the immune response and generally these immunosuppressants are used early on in the transplantation process to prevent rejection as well as in long-term maintenance therapy. On the other hand, target molecules of biological immunosuppressants are on the surface of these immunological cells and normally in clinical immunosuppressive protocols have been used as auxiliary agents of xenobiotics to prevent rejection as well as in the treatment of acute rejection. However, these xenobiotics and biological agents have multiple side effects; that is why there has been a search for new drugs to minimise these side effects and to improve patients’ quality of life. In this way, new biological agents have been proposed as maintenance immunosuppressive agents. The majority of these new immunosuppressive agents are polyclonal or monoclonal antibodies and recently the so-called fusion proteins may be the start of a new era of biological immunosuppression for maintenance regimens.
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References
Chan GL, Canafax DM, Johnson CA. The therapeutic use of azathioprine in renal transplantation. Pharmacotherapy 1987; 7(5):165–177.
Mele TS, Halloran PF. The use of mycophenolate mofetil in transplant recipients. Immunopharmacology 2000; 47(2–3):215–245.
Wenger R. Cyclosporine and analogues: structural requirements for immunosuppressive activity. Transplant Proc 1986; 18(6 Suppl 5):213–218.
Reichenspurner H. Overview of tacrolimus-based immunosuppression after heart or lung transplantation. J Heart Lung Transplant 2005; 24(2):119–130.
Knight SR, Morris PJ. The clinical benefits of cyclosporine C2-level monitoring: a systematic review. Transplantation 2007; 83(12):1525–1535.
Chapman JR, Nankivell BJ. Nephrotoxicity of ciclosporin A: short-term gain, long-term pain? Nephrol Dial Transplant 2006; 21(8):2060–2063.
Guba M, Graeb C, Jauch KW et al. Pro. and anti-cancer effects of immunosuppressive agents used in organ transplantation. Transplantation 2004; 77(12):1777–1782.
Saunders RN, Metcalfe MS, Nicholson ML. Rapamycin in transplantation: a review of the evidence. Kidney Int 2001; 59(1):3–16.
Pascual J. Everolimus in clinical practice—renal transplantation. Nephrol Dial Transplant 2006; 21 Suppl 3:iii18–iii23.
Lopez M, Clakson MR, Albin M et al. A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T-cells. J Am Soc Nephrol 2006; 17:2844–2853.
Naujokat C, Berges C, Fuchs D et al. Antithymocyte globulins suppress dendritic cell function by multiple mechanisms. Transplantation 2007; 83:485–497.
Webster AC, Pankhurst T, Rinaldi F et al. Monoclonal and polyclonal antibody therapy for treating acute rejection in kidney transplant recipients: a systematic review of randomized trial data. Transplantation 2006; 81:953–965.
de Fijter JW, Mallat MJ, Doxiadis II et al. Increased immunogenicity and cause of graft loss of old donor kidneys. J Am Soc Nephrol 2001; 12:1538–1546.
Hammer C, Thein E. Visualization of the effect of polyclonal antithymocyte globulins on adhesion of leukocytes. Transplant Proc 2002; 34:2486–2487.
Goggins WC, Pascual MA, Powelson JA et al. A prospective, randomized, clinical trial of intraoperative versus postoperative thymoglobulin in adult cadaveric renal transplant recipients. Transplantation 2003; 76:798–802.
Brennan DC, Daller JA, Lake KD et al. Thymoglobulin induction study group. Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J Med 2006; 355:1967–1977.
Stratta RJ, Sundberg AK, Rohr MS et al. Optimal use of older donors and recipients in kidney transplantation. Surgery 2006; 139:324–333.
Cruzado JM, Bestard O, Riera L et al. Immunosuppression for dual kidney transplantation with marginal organs: the old is better yet. Am J Transplant 2007; 7:639–644.
Matas AJ, Kandaswamy R, Gillingham KJ et al. Prednisone-free maintenance immunosuppression-a 5-year experience. Am J Transplant 2005; 5:2473–2478.
Kandaswamy R, Melancon JK, Dunn T et al. A prospective randomized trial of steroid-free maintenance regimens in kidney transplant recipients—an interim analysis. Am J Transplant 2005; 5:1529–1536.
Laftavi MR, Stephan R, Stefanick B et al. Randomized prospective trial of early steroid withdrawal compared with low-dose steroids in renal transplant recipients using serial protocol biopsies to assess efficacy and safety. Surgery 2005; 137:364–371.
Woodle ES, Alloway RR, Buell JF et al. Multivariate analysis of risk factors for acute rejection in early corticosteroid cessation regimens under modern immunosuppression. Am J Transplant 2005; 5:2740–2744.
Zanker B, Schneeberger H, Rothenpieler U et al. Mycophenolate mofetil-based, cyclosporine-free induction and maintenance immunosuppression: first-3-months analysis of efficacy and safety in two cohorts of renal allograft recipients. Transplantation 1998; 66:44–49.
Grinyó JM, Gil-Vernet S, Seron D et al. Primary immunosuppression with mycophenolate mofetil and antithymocyte globulin for kidney transplant recipients of a suboptimal graft. Nephrol Dial Transplant 1998; 13:2601–2604.
Larson TS, Dean PG, Stegall MD et al. Complete avoidance of calcineurin inhibitors in renal transplantation: a randomized trial comparing sirolimus and tacrolimus. Am J Transplant 2006; 6:514–522.
Lo A, Egidi MF, Gaber LW et al. Comparison of sirolimus-based calcineurin inhibitor-sparing and calcineurin inhibitor-free regimens in cadaveric renal transplantation. Transplantation 2004; 77:1228–1235.
Büchler M, Caillard S, Barbier S et al. SPIESSER group. Sirolimus versus cyclosporine in kidney recipients receiving thymoglobulin, mycophenolate mofetil and a 6-month course of steroids. Am J Transplant 2007; 7:2522–2531.
Ellis D, Shapiro R, Moritz M et al. Renal transplantation in children managed with lymphocyte depleting agents and low-dose maintenance tacrolimus monotherapy. Transplantation 2007; 83:1563–1570.
Swanson SJ, Hale DA, Mannon RB et al. Kidney transplantation with rabbit antithymocyte globulin induction and sirolimus monotherapy. Lancet 2002; 360:1662–1664.
Bestard O, Cruzado JM, Mestre M et al. Achieving donor-specific hyporesponsiveness is associated with FOXP3+ regulatory T-cell recruitment in human renal allograft infiltrates. J Immunol 2007; 179:4901–4909.
Flechner SM, Goldfarb D, Modlin C et al. Kidney transplantation without calcineurin inhibitor drugs: a prospective, randomized trial of sirolimus versus cyclosporine. Transplantation 2002; 74(8):1070–1076.
Vincenti F, Ramos E, Brattstrom C et al. Mlticenter trial exploring calcineurin inhibitors avoidance in renal transplantation. Transplantation 2001; 1:1282–1287.
Ekberg H, TedescoSilva H, Demirbas A et al. ELITE-symphony study. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007; 357:2562–2575.
Vincenti F, Schena FP, Paraskevas S et al. FREEDOM study group. A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients. Am J Transplant 2008; 8:307–316.
Akalin E. Immunosuppression minimization protocols: how should they be monitored? Nat Clin Pract Nephrol 2008; 4:484–485.
Larsen CP, Pearson TC, Adams AB et al. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant 2005; 5:443–453.
Vincenti F, Larsen C, Durrbach A et al. Belatacept study group. Costimulation blockade with belatacept in renal transplantation. N Engl J Med 2005; 353:770–781.
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Grinyó, J.M., Cruzado, J.M., Bestard, O., Vidal Castiñeira, J.R., Torras, J. (2012). Immunosuppression in the ERA of Biological Agents. In: López-Larrea, C., López-Vázquez, A., Suárez-Álvarez, B. (eds) Stem Cell Transplantation. Advances in Experimental Medicine and Biology, vol 741. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-2098-9_5
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