Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Induction immunosuppressive therapy in renal transplantation in adults

Daniel C Brennan, MD, FACP
Section Editor
Barbara Murphy, MB, BAO, BCh, FRCPI
Deputy Editor
Albert Q Lam, MD


Induction therapy is intense immunosuppressive therapy administered at the time of kidney transplantation to reduce the risk of acute allograft rejection. In general, induction immunosuppressive strategies utilized by kidney transplant centers fall into one of two categories. One strategy relies upon high doses of conventional immunosuppressive agents, while the other utilizes antibodies directed against T-cell antigens in combination with lower doses of conventional agents.

The optimal prophylactic induction immunosuppressive therapy to prevent kidney transplant rejection remains controversial [1,2]. Our approach to induction therapy in adults undergoing kidney transplantation is discussed in this topic. Maintenance immunosuppressive therapy is discussed separately. (See "Maintenance immunosuppressive therapy in renal transplantation in adults".)


Practically all kidney allograft recipients require immunosuppressive therapy to prevent rejection and loss of the allograft. The optimal regimen, including induction therapy, is not clear. A large number of controlled, randomized trials and meta-analyses indicate that induction therapy consisting of biologic antibodies plus conventional immunosuppressive agent therapy is superior to conventional agent therapy alone in reducing kidney allograft rejection and allograft failure [3-6]. (See 'rATG-Thymoglobulin versus no induction' below.)

Among patients undergoing kidney transplantation, we therefore recommend induction therapy consisting of antibody therapy plus conventional immunosuppressive therapy (table 1). One exception is Caucasian recipients of two-haplotype-identical, living, related allografts. Such patients do not generally require induction therapy with antibodies given their markedly decreased immunologic risk of acute rejection. (See 'Patients who do not require antibody induction therapy' below.)

Conventional immunosuppressive therapy is discussed elsewhere. (See "Maintenance immunosuppressive therapy in renal transplantation in adults".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jul 06, 2017.
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 ©2017 UpToDate, Inc.
  1. Kahan BD. Individuality: the barrier to optimal immunosuppression. Nat Rev Immunol 2003; 3:831.
  2. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009; 9 Suppl 3:S1.
  3. Webster AC, Playford EG, Higgins G, et al. Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials. Transplantation 2004; 77:166.
  4. Szczech LA, Berlin JA, Aradhye S, et al. Effect of anti-lymphocyte induction therapy on renal allograft survival: a meta-analysis. J Am Soc Nephrol 1997; 8:1771.
  5. Szczech LA, Berlin JA, Feldman HI. The effect of antilymphocyte induction therapy on renal allograft survival. A meta-analysis of individual patient-level data. Anti-Lymphocyte Antibody Induction Therapy Study Group. Ann Intern Med 1998; 128:817.
  6. Cai J, Terasaki PI. Induction immunosuppression improves long-term graft and patient outcome in organ transplantation: an analysis of United Network for Organ Sharing registry data. Transplantation 2010; 90:1511.
  7. Brennan DC, Daller JA, Lake KD, et al. Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J Med 2006; 355:1967.
  8. Hardinger KL, Brennan DC, Schnitzler MA. Rabbit antithymocyte globulin is more beneficial in standard kidney than in extended donor recipients. Transplantation 2009; 87:1372.
  9. Miller JT, Collins CD, Stuckey LJ, et al. Clinical and economic outcomes of rabbit antithymocyte globulin induction in adults who received kidney transplants from living unrelated donors and received cyclosporine-based immunosuppression. Pharmacotherapy 2009; 29:1166.
  10. Wiland AM, Fink JC, Weir MR, et al. Should living-unrelated renal transplant recipients receive antibody induction? Results of a clinical experience trial. Transplantation 2004; 77:422.
  11. Cassuto JR, Levine MH, Reese PP, et al. The influence of induction therapy for kidney transplantation after a non-renal transplant. Clin J Am Soc Nephrol 2012; 7:158.
  12. Vincenti F, Kirkman R, Light S, et al. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. N Engl J Med 1998; 338:161.
  13. Starzl TE, Murase N, Abu-Elmagd K, et al. Tolerogenic immunosuppression for organ transplantation. Lancet 2003; 361:1502.
  14. Webster AC, Ruster LP, McGee R, et al. Interleukin 2 receptor antagonists for kidney transplant recipients. Cochrane Database Syst Rev 2010; :CD003897.
  15. Tanriover B, Jaikaransingh V, MacConmara MP, et al. Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate. Clin J Am Soc Nephrol 2016; 11:1650.
  16. Koyawala N, Silber JH, Rosenbaum PR, et al. Comparing Outcomes between Antibody Induction Therapies in Kidney Transplantation. J Am Soc Nephrol 2017; 28:2188.
  17. Locke JE, James NT, Mannon RB, et al. Immunosuppression regimen and the risk of acute rejection in HIV-infected kidney transplant recipients. Transplantation 2014; 97:446.
  18. Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med 2010; 363:2004.
  19. Carter JT, Melcher ML, Carlson LL, et al. Thymoglobulin-associated Cd4+ T-cell depletion and infection risk in HIV-infected renal transplant recipients. Am J Transplant 2006; 6:753.
  20. Kucirka LM, Durand CM, Bae S, et al. Induction Immunosuppression and Clinical Outcomes in Kidney Transplant Recipients Infected With Human Immunodeficiency Virus. Am J Transplant 2016; 16:2368.
  21. Kirk AD. Induction immunosuppression. Transplantation 2006; 82:593.
  22. Mourad G, Garrigue V, Squifflet JP, et al. Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression. Transplantation 2001; 72:1050.
  23. Charpentier B, Rostaing L, Berthoux F, et al. A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients. Transplantation 2003; 75:844.
  24. Brennan DC, Flavin K, Lowell JA, et al. A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation 1999; 67:1011.
  25. Brennan DC, Schnitzler MA. Long-term results of rabbit antithymocyte globulin and basiliximab induction. N Engl J Med 2008; 359:1736.
  26. Knight RJ, Kerman RH, Schoenberg L, et al. The selective use of basiliximab versus thymoglobulin in combination with sirolimus for cadaveric renal transplant recipients at low risk versus high risk for delayed graft function. Transplantation 2004; 78:904.
  27. Mourad G, Rostaing L, Legendre C, et al. Sequential protocols using basiliximab versus antithymocyte globulins in renal-transplant patients receiving mycophenolate mofetil and steroids. Transplantation 2004; 78:584.
  28. Willoughby LM, Schnitzler MA, Brennan DC, et al. Early outcomes of thymoglobulin and basiliximab induction in kidney transplantation: application of statistical approaches to reduce bias in observational comparisons. Transplantation 2009; 87:1520.
  29. Kim JM, Jang HR, Kwon CH, et al. Rabbit antithymocyte globulin compared with basiliximab in kidney transplantation: a single-center study. Transplant Proc 2012; 44:167.
  30. Haririan A, Morawski K, Sillix DH, et al. Induction therapy with basiliximab versus Thymoglobulin in African-American kidney transplant recipients. Transplantation 2005; 79:716.
  31. Opelz G, Unterrainer C, Süsal C, Döhler B. Efficacy and safety of antibody induction therapy in the current era of kidney transplantation. Nephrol Dial Transplant 2016; 31:1730.
  32. Brokhof MM, Sollinger HW, Hager DR, et al. Antithymocyte globulin is associated with a lower incidence of de novo donor-specific antibodies in moderately sensitized renal transplant recipients. Transplantation 2014; 97:612.
  33. 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.
  34. Agha IA, Rueda J, Alvarez A, et al. Short course induction immunosuppression with thymoglobulin for renal transplant recipients. Transplantation 2002; 73:473.
  35. Shapiro R, Jordan ML, Basu A, et al. Kidney transplantation under a tolerogenic regimen of recipient pretreatment and low-dose postoperative immunosuppression with subsequent weaning. Ann Surg 2003; 238:520.
  36. Ruggenenti P, Codreanu I, Cravedi P, et al. Basiliximab combined with low-dose rabbit anti-human thymocyte globulin: a possible further step toward effective and minimally toxic T cell-targeted therapy in kidney transplantation. Clin J Am Soc Nephrol 2006; 1:546.
  37. Peddi VR, Bryant M, Roy-Chaudhury P, et al. Safety, efficacy, and cost analysis of thymoglobulin induction therapy with intermittent dosing based on CD3+ lymphocyte counts in kidney and kidney-pancreas transplant recipients. Transplantation 2002; 73:1514.
  38. Stratta RJ, Sundberg AK, Farney AC, et al. Experience with alternate-day thymoglobulin induction in pancreas transplantation with portal-enteric drainage. Transplant Proc 2005; 37:3546.
  39. Wong W, Agrawal N, Pascual M, et al. Comparison of two dosages of thymoglobulin used as a short-course for induction in kidney transplantation. Transpl Int 2006; 19:629.
  40. Gurk-Turner C, Airee R, Philosophe B, et al. Thymoglobulin dose optimization for induction therapy in high risk kidney transplant recipients. Transplantation 2008; 85:1425.
  41. Stevens RB, Mercer DF, Grant WJ, et al. Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report. Transplantation 2008; 85:1391.
  42. Préville X, Flacher M, LeMauff B, et al. Mechanisms involved in antithymocyte globulin immunosuppressive activity in a nonhuman primate model. Transplantation 2001; 71:460.
  43. Hardinger KL, Schnitzler MA, Koch MJ, et al. Thymoglobulin induction is safe and effective in live-donor renal transplantation: a single center experience. Transplantation 2006; 81:1285.
  44. Martin ST, Roberts KL, Malek SK, et al. Induction treatment with rabbit antithymocyte globulin versus basiliximab in renal transplant recipients with planned early steroid withdrawal. Pharmacotherapy 2011; 31:566.
  45. Libório AB, Mendoza TR, Esmeraldo RM, et al. Induction antibody therapy in renal transplantation using early steroid withdrawal: long-term results comparing anti-IL2 receptor and anti-thymocyte globulin. Int Immunopharmacol 2011; 11:1832.
  46. Thomusch O, Wiesener M, Opgenoorth M, et al. Rabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal transplantation (Harmony): an open-label, multicentre, randomised controlled trial. Lancet 2016; 388:3006.
  47. Lebranchu Y, Bridoux F, Büchler M, et al. Immunoprophylaxis with basiliximab compared with antithymocyte globulin in renal transplant patients receiving MMF-containing triple therapy. Am J Transplant 2002; 2:48.
  48. Al Najjar A, Etienne I, Le Pogamp P, et al. Long-term results of monoclonal anti-Il2-receptor antibody versus polyclonal antilymphocyte antibodies as induction therapy in renal transplantation. Transplant Proc 2006; 38:2298.
  49. Novartis October 6, 2000 "Dear Healthcare Provider" letter.
  50. Baudouin V, Crusiaux A, Haddad E, et al. Anaphylactic shock caused by immunoglobulin E sensitization after retreatment with the chimeric anti-interleukin-2 receptor monoclonal antibody basiliximab. Transplantation 2003; 76:459.
  51. Barros VR, Rocha V, Garcia VD, Garcia CD. Anaphylactic shock after retreatment with basiliximab. Transplant Proc 2003; 35:579.
  52. Calne R, Moffatt SD, Friend PJ, et al. Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients. Transplantation 1999; 68:1613.
  53. Kirk AD, Hale DA, Mannon RB, et al. Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation 2003; 76:120.
  54. Tan HP, Kaczorowski DJ, Basu A, et al. Living-related donor renal transplantation in HIV+ recipients using alemtuzumab preconditioning and steroid-free tacrolimus monotherapy: a single center preliminary experience. Transplantation 2004; 78:1683.
  55. Watson CJ, Bradley JA, Friend PJ, et al. Alemtuzumab (CAMPATH 1H) induction therapy in cadaveric kidney transplantation--efficacy and safety at five years. Am J Transplant 2005; 5:1347.
  56. Vathsala A, Ona ET, Tan SY, et al. Randomized trial of Alemtuzumab for prevention of graft rejection and preservation of renal function after kidney transplantation. Transplantation 2005; 80:765.
  57. Ciancio G, Burke GW, Gaynor JJ, et al. A randomized trial of three renal transplant induction antibodies: early comparison of tacrolimus, mycophenolate mofetil, and steroid dosing, and newer immune-monitoring. Transplantation 2005; 80:457.
  58. Morris PJ, Russell NK. Alemtuzumab (Campath-1H): a systematic review in organ transplantation. Transplantation 2006; 81:1361.
  59. Knechtle SJ, Fernandez LA, Pirsch JD, et al. Campath-1H in renal transplantation: The University of Wisconsin experience. Surgery 2004; 136:754.
  60. Shapiro R, Basu A, Tan H, et al. Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with Thymoglobulin or Campath. J Am Coll Surg 2005; 200:505.
  61. Kaufman DB, Leventhal JR, Axelrod D, et al. Alemtuzumab induction and prednisone-free maintenance immunotherapy in kidney transplantation: comparison with basiliximab induction--long-term results. Am J Transplant 2005; 5:2539.
  62. Ciancio G, Burke GW, Gaynor JJ, et al. The use of Campath-1H as induction therapy in renal transplantation: preliminary results. Transplantation 2004; 78:426.
  63. Tan HP, Kaczorowski DJ, Basu A, et al. Living donor renal transplantation using alemtuzumab induction and tacrolimus monotherapy. Am J Transplant 2006; 6:2409.
  64. Ciancio G, Burke GW 3rd. Alemtuzumab (Campath-1H) in kidney transplantation. Am J Transplant 2008; 8:15.
  65. Ciancio G, Burke GW, Gaynor JJ, et al. Campath-1H induction therapy in African American and Hispanic first renal transplant recipients: 3-year actuarial follow-up. Transplantation 2008; 85:507.
  66. Ortiz J, Palma-Vargas J, Wright F, et al. Campath induction for kidney transplantation: report of 297 cases. Transplantation 2008; 85:1550.
  67. Tan HP, Donaldson J, Basu A, et al. Two hundred living donor kidney transplantations under alemtuzumab induction and tacrolimus monotherapy: 3-year follow-up. Am J Transplant 2009; 9:355.
  68. Pascual J, Mezrich JD, Djamali A, et al. Alemtuzumab induction and recurrence of glomerular disease after kidney transplantation. Transplantation 2007; 83:1429.
  69. Hanaway MJ, Woodle ES, Mulgaonkar S, et al. Alemtuzumab induction in renal transplantation. N Engl J Med 2011; 364:1909.
  70. http://www.usrds.org/2009/pdf/V2_07_09.pdf (Accessed on October 01, 2014).
  71. Ciancio G, Burke GW, Gaynor JJ, et al. A randomized trial of thymoglobulin vs. alemtuzumab (with lower dose maintenance immunosuppression) vs. daclizumab in renal transplantation at 24 months of follow-up. Clin Transplant 2008; 22:200.
  72. Sureshkumar KK, Thai NL, Hussain SM, et al. Influence of induction modality on the outcome of deceased donor kidney transplant recipients discharged on steroid-free maintenance immunosuppression. Transplantation 2012; 93:799.
  73. 3C Study Collaborative Group, Haynes R, Harden P, et al. Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet 2014; 384:1684.
  74. Farney A, Sundberg A, Moore P, et al. A randomized trial of alemtuzumab vs. anti-thymocyte globulin induction in renal and pancreas transplantation. Clin Transplant 2008; 22:41.
  75. Farney AC, Doares W, Rogers J, et al. A randomized trial of alemtuzumab versus antithymocyte globulin induction in renal and pancreas transplantation. Transplantation 2009; 88:810.
  76. Haider I, Cahill M. Fatal thrombocytopaenia temporally related to the administration of alemtuzumab (MabCampath) for refractory CLL despite early discontinuation of therapy. Hematology 2004; 9:409.
  77. Kirk AD, Hale DA, Swanson SJ, Mannon RB. Autoimmune thyroid disease after renal transplantation using depletional induction with alemtuzumab. Am J Transplant 2006; 6:1084.
  78. Pearl JP, Parris J, Hale DA, et al. Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion. Am J Transplant 2005; 5:465.
  79. Tydén G, Genberg H, Tollemar J, et al. A randomized, doubleblind, placebo-controlled, study of single-dose rituximab as induction in renal transplantation. Transplantation 2009; 87:1325.
  80. Tydén G, Ekberg H, Tufveson G, Mjörnstedt L. A randomized, double-blind, placebo-controlled study of single dose rituximab as induction in renal transplantation: a 3-year follow-up. Transplantation 2012; 94:e21.
  81. Kyaw T, Tay C, Krishnamurthi S, et al. B1a B lymphocytes are atheroprotective by secreting natural IgM that increases IgM deposits and reduces necrotic cores in atherosclerotic lesions. Circ Res 2011; 109:830.
  82. van den Hoogen MW, Kamburova EG, Baas MC, et al. Rituximab as induction therapy after renal transplantation: a randomized, double-blind, placebo-controlled study of efficacy and safety. Am J Transplant 2015; 15:407.
  83. Macklin PS, Morris PJ, Knight SR. A systematic review of the use of rituximab for desensitization in renal transplantation. Transplantation 2014; 98:794.
  84. Tan J, Wu W, Xu X, et al. Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA 2012; 307:1169.