Advertisement

Drugs

, Volume 69, Issue 11, pp 1483–1512 | Cite as

Rabbit Antithymocyte Globulin (Thymoglobulin®)

A Review of its Use in the Prevention and Treatment of Acute Renal Allograft Rejection
Adis Drug Evaluation

Summary

Abstract

Rabbit antithymocyte globulin (rATG) [Thymoglobulin®; Thymoglobuline®] is a purified, pasteurized preparation of polyclonal gamma immunoglobulin raised in rabbits against human thymocytes that is indicated for the prevention and/or treatment of renal transplant rejection in several countries worldwide.

rATG induction in combination with immunosuppressive therapy is more effective in preventing episodes of acute renal graft rejection in adult renal transplant recipients than immunosuppressive therapy without induction. The efficacy of rATG induction is generally better than that of equine antithymocyte globulin (eATG) induction and generally no different from that of basiliximab or low-dose daclizumab induction in this patient population. However, in high-risk patients, rATG induction was more effective than daclizumab or basiliximab induction in preventing acute renal graft rejection. In the treatment of renal graft rejection in adult renal transplant recipients, rATG was more effective than eATG in terms of the successful response rate, although the agents generally did not differ with regard to most other endpoints.

Both induction and treatment with rATG are generally well tolerated, although adverse events, such as fever, leukopenia and thrombocytopenia, appear more common with rATG than with other antibody preparations. The overall incidence of infection associated with rATG induction was generally no different from that seen with eATG or basiliximab induction, although was higher with rATG than with basiliximab in high-risk patients. The incidence of cytomegalovirus (CMV) disease generally did not differ between rATG and eATG induction, and there was no significant difference between rATG and daclizumab induction with regard to the incidence of CMV infections or the proportion of patients who received treatment for a CMV episode or infection. Relative to basiliximab, the incidence of CMV infection was generally higher with rATG, except in high-risk patients. In the treatment of acute renal rejection, the nature and incidence of infections were generally similar with rATG and eATG. The incidence of malignancies is generally low with rATG therapy and generally does not differ from that seen with other agents.

Further prospective comparative studies would be beneficial in order to definitively position rATG with respect to other antibody preparations. In the meantime, available clinical data suggest that rATG is an effective and generally well tolerated option for the prevention and treatment of acute renal graft rejection in renal transplant recipients.

Pharmacological Properties

rATG displays specificity towards a wide variety of surface antigens on both immune system and endothelial cells. The precise mechanism(s) of action underlying its immunosuppressive efficacy is unclear, although T-cell depletion is considered to play a key role. Other mechanisms include lymphocyte surface antigen modulation, transcription factor activation, and interference with processes of immune system cells, such as cytokine production, chemotaxis, endocytosis, stimulation and proliferation. rATG may also induce apoptosis, antibody-dependent lysis or complement-mediated lysis of various immune system cells, and negate leukocyte-endothelial cell adhesion. Treatment with rATG sustained T-cell depletion more effectively than eATG in renal transplant recipients experiencing acute renal rejection. Moreover, rATG induction was at least as effective as eATG induction in depleting lymphocytes, and as expected, was associated with lower lymphocyte levels than basiliximab or daclizumab induction in renal transplant recipients.

Serum concentrations of rATG appear to increase during treatment with intravenous rATG, and the serum concentration of total rATG, but not active rATG, is closely related to the cumulative dose. Levels of rATG in serum decline steadily after infusion cessation, with an elimination half-life of 2–3 days after an initial dose of 1.25–1.5mg/kg, although the decline of active rATG levels appears to be more rapid. Among renal transplant patients who received rATG 1.5mg/kg/day for up to 14 days, rATG and active rATG were present at measurable levels in 81% and 12% of patients 90 days after initiation of therapy.

Therapeutic Efficacy

Prevention of Acute Renal Transplant Rejection: In two randomized, open-label, multicentre trials in adult renal transplant recipients, rATG induction in combination with tacrolimus-based immunosuppressive therapy was more effective than tacrolimus-based therapy without induction in preventing acute renal graft rejection at 6 or 12 months post-transplantation. In one of these studies, the incidence of biopsy-confirmed acute rejection (BCAR) in recipients of rATG induction with tacrolimus-based therapy did not significantly differ from that seen in recipients of rATG induction with ciclosporin-based therapy. Moreover, the median time to BCAR was >1 week longer with rATG induction therapy than with noninduction therapy, although there were no significant differences between regimens in terms of patient or graft survival.

rATG induction was generally more effective than eATG induction in adult renal transplant recipients receiving immunosuppressive therapy in a double-blind, single-centre trial. rATG recipients had a lower incidence of BCAR episodes and greater event-free survival than eATG recipients up to 10 years post-transplantation, and greater graft survival up to 5 years post-transplantation, although there was no significant between-group difference in terms of patient survival. Moreover, in three randomized, open-label, multicentre studies, the efficacy of rATG induction therapy was generally no different from that of basiliximab or low-dose daclizumab in adult renal transplant recipients receiving triple immunosuppressive therapy. There were generally no differences between rATG and these agents in terms of the incidence of BCAR, or patient or graft survival at 6 months or 1 year post-transplantation, with rATG and basiliximab also not differing with regard to the composite of BCAR, graft loss or death at these timepoints.

Induction with rATG was also effective in combination with corticosteroid-free immunosuppressive therapy in adult and paediatric renal transplant recipients in a prospective noncomparative study. Furthermore, rATG induction in combination with an early corticosteroid withdrawal immunosuppressive regimen provided efficacy not significantly different from that of an immunosuppressive regimen with standard corticosteroid use in adult renal transplant recipients in a randomized, multicentre trial.

rATG induction, in combination with triple immunosuppressive therapy, has also demonstrated efficacy in renal transplant recipients at high risk of acute rejection or delayed graft function. In a large, randomized, multicentre trial, the efficacy of rATG was generally no different to that of basiliximab at 1 year post-transplantation, with no significant between-group difference in the composite endpoint of first BCAR, delayed graft function, graft loss or death, or most of the individual components of the composite; however, the incidence of BCAR was lower with rATG than with basiliximab. In a similarly designed trial comparing rATG with daclizumab, rATG provided better efficacy in terms of the incidence of BCAR 1 year after transplantation and was associated with a longer median time to rejection, although the treatment groups did not significantly differ with regard to rates of patient or graft survival. Longer term, rATG may provide benefits over basiliximab up to 5 years post-transplantation, according to a retrospective analysis of one of these trials. Data from three retrospective studies indicated that rATG induction therapy is effective in African-American renal transplant recipients.

In two retrospective studies in paediatric renal transplant recipients, the efficacy of rATG in combination with immunosuppressive therapy in preventing episodes of acute rejection was not significantly different to that of immunosuppressive therapy alone or in combination with basiliximab at 1 year post-transplantation, whereas rATG was associated with fewer BCAR episodes than eATG up to 3 years post-transplantation in the largest of these studies. There were generally no differences between rATG and these regimens with regard to most other endpoints.

Treatment of Acute Renal Graft Rejection: In a large randomized, double-blind, multicentre, phase III trial conducted in adult renal transplant recipients receiving concomitant immunosuppressive therapy, more rATG than eATG recipients achieved the endpoint of successful response (i.e. a return of serum creatinine levels to baseline by end of treatment or within 14 days of treatment initiation), although the treatment groups generally did not differ in terms of graft survival at 30 days, graft function or the proportion of patients who had an improvement in rejection severity of one Banff grade. However, among those who achieved a successful response, fewer episodes of recurrent rejection occurred in rATG than eATG recipients within 90 days of treatment cessation, although there was no between-group difference in graft or patient survival 1 year after treatment completion.

Tolerability

Both induction and treatment with rATG were generally well tolerated in adult renal transplant recipients in clinical trials. More patients who received rATG induction in combination with immunosuppressive therapy experienced leukopenia, fever, serum sickness and thrombocytopenia than those who received immunosuppressive therapy without induction. In trials comparing rATG with other induction agents, rATG was associated with a lower median incidence of serious treatment-emergent adverse events than eATG, although it generally did not differ from basiliximab in terms of the incidence of any adverse events or serious adverse events, or from daclizumab in terms of the incidence or severity of adverse events. The most common selected adverse events (other than infection) reported in recipients of rATG and other induction agents were fever, gastrointestinal disorder, leukopenia and thrombocytopenia; rATG was associated with a higher incidence of leukopenia than basiliximab or eATG and a higher incidence of fever and thrombocytopenia than basiliximab in some studies. Adverse events considered to be study drug related occurred in more rATG than basiliximab induction recipients, with fever, gastrointestinal disorder, cutaneous rash and serum sickness being attributed to rATG. When used in the treatment of acute renal transplant rejection, the tolerability profile of rATG was generally similar to that of eATG, with fever, chills and leukopenia the most common adverse events reported in both treatment groups. However, compared with eATG, rATG was associated with a greater incidence of leukopenia and malaise, and a lower incidence of dizziness and dysuria.

rATG induction in combination with immunosuppressive therapy was generally less favourable than immunosuppressive therapy without induction with regard to the incidence of infection, particularly CMV. However, the overall incidence of infection associated with rATG induction was no different from that seen with eATG or basiliximab induction, although it was higher than with basiliximab in high-risk patients. In studies that assessed CMV parameters as primary tolerability endpoints, the incidence of CMV disease generally did not differ between rATG and eATG induction, and there was no significant difference between rATG and daclizumab induction with regard to the incidence of asymptomatic or symptomatic CMV infection or the proportion of patients who received treatment for a CMV episode. In other induction trials, rATG did not significantly differ from daclizumab with regard to the incidence of CMV infections that required treatment, whereas, relative to basiliximab, the incidence of CMV infection was higher with rATG in two studies, although it was lower with rATG in a study in high-risk patients. In the treatment of acute renal rejection, the nature and incidence of infections were generally similar with rATG and eATG.

The incidence of malignancies was generally low with rATG therapy, regardless of whether the drug was being administered for the prevention or treatment of renal transplant rejection, and generally did not differ from that seen with eATG, basiliximab or daclizumab. Retrospective analyses of data from three US registry databases have produced mixed findings concerning the risk of post-transplant malignancies associated with rATG and other immunosuppressive agents in renal transplant recipients.

Keywords

Renal Transplant Recipient Daclizumab Basiliximab Delay Graft Function Paediatric Renal Transplant Recipient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    National Institute for Clinical Excellence. Immunosuppressive therapy for renal transplantation in adults: technology appraisal 85 [online]. Available from URL: http://www.nice.org.uk/nicemedia/pdf/TA085guidance.pdf [Accessed 2009 Apr 1]
  2. 2.
    Knoll G. Trends in kidney transplantation over the past decade. Drugs 2008; 68 Suppl. 1: 3–10PubMedCrossRefGoogle Scholar
  3. 3.
    Grassmann A, Gioberge S, Moeller S, et al. ESRD patients in 2004: global overview of patient numbers, treatment modalities and associated trends. Nephrol Dial Transplant 2005 Dec; 20(12): 2587–93PubMedCrossRefGoogle Scholar
  4. 4.
    Weimert NA, Alloway RR. Renal transplantation in high-risk patients. Drugs 2007; 67(11): 1603–27PubMedCrossRefGoogle Scholar
  5. 5.
    Hariharan S, Johnson CP, Bresnahan BA, et al. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Eng J Med 2000 Mar 2; 342(9): 605–12CrossRefGoogle Scholar
  6. 6.
    Ciancio G, Burke GW, Miller J. Induction therapy in renal transplantation: an overview of current developments. Drugs 2007; 67(18): 2667–80PubMedCrossRefGoogle Scholar
  7. 7.
    Perico N, Remuzzi G. Prevention of transplant rejection: current treatment guidelines and future developments. Drugs 1997 Oct; 54(4): 533–70PubMedCrossRefGoogle Scholar
  8. 8.
    Hardinger KL. Rabbit antithymocyte globulin induction therapy in adult renal transplantation. Pharmacotherapy 2006 Dec; 26(12): 1771–83PubMedCrossRefGoogle Scholar
  9. 9.
    Nashan B. Antibody induction therapy in renal transplant patients receiving calcineurin-inhibitor immunosuppressive regimens: a comparative review. Biodrugs 2005; 19(1): 39–46PubMedCrossRefGoogle Scholar
  10. 10.
    Tan HP, Smaldone MC, Shapiro R. Immunosuppressive preconditioning or induction regimens: evidence to date. Drugs 2006; 66(12): 1535–45PubMedCrossRefGoogle Scholar
  11. 11.
    Genzyme Europe B.V. Thymoglobulin 25 mg powder for solution for infusion: summary of product characteristics [online]. Available from URL: http://www.emc.medicines.org.uk/emc/assets/c/html/displayDocPrinterFriendly.asp?documentid=20799 [Accessed 2009 Jan 7]
  12. 12.
    Genzyme Canada Inc. PrThymoglobulin® (anti-thymocyte globulin [rabbit]): powder for solution [online]. Available from URL: http://www.hc-sc.gc.ca [Accessed 2009 Jul 9]
  13. 13.
    Genzyme Corporation. Thymoglobulin®, antithymocyte globulin (rabbit): US prescribing information [online]. Available from URL: http://www.thymoglobulin.com/home/thymo_pdf_pi.pdf [Accessed 2008 Dec 6]
  14. 14.
    Ormrod D, Jarvis B. Antithymocyte globulin (rabbit): a review of the use of Thymoglobulin® in the prevention and treatment of acute renal allograft rejection. Biodrugs 2000 Oct; 14(4): 255–73CrossRefGoogle Scholar
  15. 15.
    Brayman K. New insights into the mechanisms of action of thymoglobulin. Transplantation 2007 Dec 15; 84 (11s Suppl.): S3–4CrossRefGoogle Scholar
  16. 16.
    Mueller TF. Mechanisms of action of thymoglobulin. Transplantation 2007 Dec 15; 84 (11S Suppl.): S5–10CrossRefGoogle Scholar
  17. 17.
    Noël C, Abramowicz D, Durand D, et al. Daclizumab versus antithymocyte globulin in high-immunological-risk renal transplant recipients. J Am Soc Nephrol 2009 Jun; 20(6): 1385–92PubMedCrossRefGoogle Scholar
  18. 18.
    Stauch D, Dernier A, Sarmiento Marchese E, et al. Targeting of natural killer cells by rabbit antithymocyte globulin and Campath-1H: similar effects independent of specificity. PLoS ONE 2009 Mar; 4(3): E4709PubMedCrossRefGoogle Scholar
  19. 19.
    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 Jan; 2(1): 48–56PubMedCrossRefGoogle Scholar
  20. 20.
    Gaber AO, First MR, Tesi RJ, et al. Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation. Transplantation 1998 Jul 15; 66(1): 29–37PubMedCrossRefGoogle Scholar
  21. 21.
    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 [published erratum appeared in Transplantation 1999 May 27; 67 (10): 1386]. Transplantation 1999 Apr 15; 67(7): 1011–8PubMedCrossRefGoogle Scholar
  22. 22.
    Leffell MS, Kopchliiska D, Lucas DP, et al. Effect of induction agent on cellular and humoral responses to renal transplants in sensitized patients [abstract no. 14]. Am J Transplant 2008 May; 8 (Suppl. 2): 182Google Scholar
  23. 23.
    Vallotton L, Hadaya K, Ciuffreda D, et al. Prospective monitoring of a CD4+ CD25high CD45RO+ CD127high T cell population after first kidney transplantation following thymoglobulin or basiliximab induction [abstract no. 1108]. Am J Transplantation 2008 May; 8 (Suppl. 2): 473Google Scholar
  24. 24.
    Lobo PI, Isaacs RB, Spencer C, et al. Polyclonal rabbit antithymocyte globulins fails to inhibit memory B cell activation or plasma cell (RATG) in-vivo [abstract no. 1218]. World Transplant Congress: The First Joint International Transplant Meeting; 2006 Jul 22–27; Boston (MA)Google Scholar
  25. 25.
    Conti DJ, Elbahloul O, Gallichio MH. Coagulopathy associated with thymoglobulin induction therapy following renal transplantation [abstract no. 1299]. Am J Transplantation 2008 May; 8 (Suppl. 2): 524Google Scholar
  26. 26.
    Sewgobind VDKD, Kho MML, van der Laan LJW, et al. Anti-thymocyte globulin induction therapy favors the generation of memory CD4+FoxP3+ CD127-/low regulatory T cells in patients after kidney transplantation [abstract no. 417]. Am J Transplantation 2008 May 1; 8 (Suppl. 2): 290Google Scholar
  27. 27.
    Guttmann RD, Caudrelier P, Alberici G, et al. Pharmacokinetics, foreign protein immune response, cytokine release, and lymphocyte subsets in patients receiving thymoglobuline and immunosuppression. Transplant Proc 1997 Nov; 29(7A): 24–6SCrossRefGoogle Scholar
  28. 28.
    Liu Z, Fang Y, Wang X, et al. Upregulation of molecules associated with T-regulatory function by thymoglobulin pretreatment of human CD4+ cells. Transplantation 2008 Nov 27; 86(10): 1419–26PubMedCrossRefGoogle Scholar
  29. 29.
    Dalle J-H, Dardari R, Menezes J, et al. Binding of thymoglobulin to natural killer cells leads to cell activation and interferon-γ production. Transplantation 2009 Feb 27; 87(4): 473–81PubMedCrossRefGoogle Scholar
  30. 30.
    LaCorcia G, Swistak M, Lawendowski C, et al. Polyclonal rabbit antithymocyte globulin exhibits consistent immunosuppressive capabilities beyond cell depletion. Transplantation 2009 Apr 15; 87(7): 966–74PubMedCrossRefGoogle Scholar
  31. 31.
    Naujokat C, Berges C, Fuchs D, et al. Antithymocyte globulins suppress dendritic cell function by multiple mechanisms. Transplantation 2007 Feb 27; 83(4): 485–97PubMedCrossRefGoogle Scholar
  32. 32.
    Lopez M, Clarkson 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 Oct; 17(10): 2844–53PubMedCrossRefGoogle Scholar
  33. 33.
    Michallet MC, Preville X, Flacher M, et al. Functional antibodies to leukocyte adhesion molecules in antithymocyte globulins. Transplantation 2003 Mar 15; 75(5): 657–62PubMedCrossRefGoogle Scholar
  34. 34.
    Genestier L, Fournel S, Flacher M, et al. Induction of Fas (Apo-1, CD95)-mediated apoptosis of activated lymphocytes by polyclonal antithymocyte globulins. Blood 1998 Apr 1; 91(7): 2360–8PubMedGoogle Scholar
  35. 35.
    Piaggio G, Podestá M, Pitto A, et al. Comparable TNF-alpha, IFN-gamma and GM-CSF production by purified normal marrow CD3 cells in response to horse antilymphocyte and rabbit antithymocyte globulin. Eur J Haematol 1998 Apr; 60(4): 240–4PubMedCrossRefGoogle Scholar
  36. 36.
    Zand MS, Vo T, Huggins J, et al. Polyclonal rabbit antithymocyte globulin triggers B-cell and plasma cell apoptosis by multiple pathways. Transplantation 2005 Jun 15; 79(11): 1507–15PubMedCrossRefGoogle Scholar
  37. 37.
    Chappell D, Beiras-Fernandez A, Hammer C, et al. In vivo visualization of the effect of polyclonal antithymocyte globulins on the microcirculation after ischemia/reperfusion in a primate model. Transplantation 2006 Feb 27; 81(4): 552–8PubMedCrossRefGoogle Scholar
  38. 38.
    Préville X, Flacher M, LeMauff B, et al. Mechanisms involved in antithymocyte globulin immunosuppressive activity in a nonhuman primate model. Transplantation 2001 Feb 15; 71(3): 460–8PubMedCrossRefGoogle Scholar
  39. 39.
    Woodle ES, TRIMS Study Group. A randomized, prospective, multicenter comparative study evaluating a thymoglobulin-based early corticosteroid cessation regimen in renal transplantation [abstract no. 673]. World Transplant Congress: The First Joint International Transplant Meeting; 2006 Jul 22-27; Boston (MA)Google Scholar
  40. 40.
    Oluwole SF, Oluwole OO, DePaz HA, et al. CD4+CD25+ regulatory T cells mediate acquired transplant tolerance. Transpl Immunol 2003 Jul 30; 11(3–4): 287–93PubMedCrossRefGoogle Scholar
  41. 41.
    Taams L, Vukmanovic-Stejic M, Salmon M, et al. Immune regulation by CD4+CD25+ regulatory T cells: implications for transplantation tolerance. Transpl Immunol 2003 Jul 30; 11(3–4): 277–85PubMedCrossRefGoogle Scholar
  42. 42.
    Hardinger KL, Schnitzler MA, Miller B, et al. Five-year follow up of thymoglobulin versus ATGAM induction in adult renal transplantation. Transplantation 2004 Jul 15; 78(1): 136–41PubMedCrossRefGoogle Scholar
  43. 43.
    Regan JF, Lyonnais C, Campbell K, et al. Total and active thymoglobulin levels: effects of dose and sensitization on serum concentrations. Transpl Immunol 2001 Oct; 9(1): 29–36PubMedCrossRefGoogle Scholar
  44. 44.
    Khositseth S, Matas A, Cook ME, et al. Thymoglobulin versus ATGAM induction therapy in pediatric kidney transplant recipients: a single-center report. Transplantation 2005 Apr 27; 79(8): 958–63PubMedCrossRefGoogle Scholar
  45. 45.
    Baron PW, Ojogho ON, Yorgin P, et al. Comparison of outcomes with low-dose anti-thymocyte globulin, basiliximab or no induction therapy in pediatric kidney transplant recipients: a retrospective study. Pediatr Transplant 2008 Feb; 12(1): 32–9PubMedCrossRefGoogle Scholar
  46. 46.
    Haririan A, Morawski K, Sillix DH, et al. Induction therapy with basiliximab versus Thymoglobulin in African-American kidney transplant recipients. Transplantation 2005 Mar 27; 79(6): 716–21PubMedCrossRefGoogle Scholar
  47. 47.
    Haririan A, Sillix DH, Morawski K, et al. Short-term experience with early steroid withdrawal in African-American renal transplant recipients. Am J Transplant 2006 Oct; 6(10): 2396–402PubMedCrossRefGoogle Scholar
  48. 48.
    Hammond EB, Taber DJ, Weimert NA, et al. Efficacy of induction therapy on acute rejection and graft outcomes in African American kidney transplantation. Clin Transplant. Epub 2009 Feb 19Google Scholar
  49. 49.
    Locke JE, Simpkins CE, Leffell MS, et al. Induction immunosuppression in crossmatch positive renal transplant recipients: results of a randomized controlled clinical trial [abstract no 176]. Am J Transplant 2009 May; 9 Suppl. 2: 241Google Scholar
  50. 50.
    Hardinger KL, Rhee S, Buchanan P, et al. A prospective, randomized, double-blinded comparison of thymoglobulin versus Atgam for induction immunosuppressive therapy: 10-year results. Transplantation 2008 Oct 15; 86(7): 947–52PubMedCrossRefGoogle Scholar
  51. 51.
    Hardinger KL, Brennan DC, Schnitzler MA. Rabbit antithymocyte globulin is more beneficial in standard kidney than in extended donor recipients. Transplantation 2009 May 15; 87(9): 1372–6PubMedCrossRefGoogle Scholar
  52. 52.
    Brennan DC, Schnitzler MA. Long-term results of rabbit antithymocyte globulin and basiliximab induction [letter]. N Engl J Med 2008 Oct 16; 359(16): 1736–8PubMedCrossRefGoogle Scholar
  53. 53.
    Brennan DC, Daller JA, Lake KD, et al. Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J Med 2006 Nov 9; 355(19): 1967–77PubMedCrossRefGoogle Scholar
  54. 54.
    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 Mar 27; 75(6): 844–51PubMedCrossRefGoogle Scholar
  55. 55.
    Mourad G, Garrigue V, Squifflet J-P, et al. Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression. Transplantation 2001 Sep 27; 72: 1050–5PubMedCrossRefGoogle Scholar
  56. 56.
    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 Aug 27; 78(4): 584–90PubMedCrossRefGoogle Scholar
  57. 57.
    Abou-Ayache R, Büchler M, Lepogamp P, et al. CMV infections after two doses of daclizumab versus thymoglobulin in renal transplant patients receiving mycophenolate mofetil, steroids and delayed cyclosporine A. Nephrol Dial Transplant 2008 Jun; 23(6): 2024–32PubMedCrossRefGoogle Scholar
  58. 58.
    Birkeland SA. Steroid-free immunosuppression in renal transplantation: a long-term follow-up of 100 consecutive patients. Transplantation 2001 Apr 27; 71: 1089–90PubMedCrossRefGoogle Scholar
  59. 59.
    Matas AJ, Kandaswamy R, Gillingham KJ, et al. Prednisone-free maintenance immunosuppression: a 5-year experience. Am J Transplant 2005 Oct; 5(10): 2473–8PubMedCrossRefGoogle Scholar
  60. 60.
    Rajab A, Pelletier RP, Henry ML, et al. Excellent clinical outcomes in primary kidney transplant recipients treated with steroid-free maintenance immunosuppression. Clin Transplant 2006 Sep–Oct; 20(5): 537–46PubMedCrossRefGoogle Scholar
  61. 61.
    Hastings MC, Wyatt RJ, Lau KK, et al. Five years’ experience with thymoglobulin induction in a pediatric renal transplant population. Pediatr Transplant 2006 Nov; 10(7): 805–10CrossRefGoogle Scholar
  62. 62.
    Ault BH, Honaker MR, Osama Gaber A, et al. Short-term outcomes of Thymoglobulin induction in pediatric renal transplant recipients. Pediatr Nephrol 2002 Oct; 17(10): 815–8PubMedCrossRefGoogle Scholar
  63. 63.
    Barletta GM, Kirk E, Gardner JJ, et al. Rapid discontinuation of corticosteroids in pediatric renal transplantation. Pediatr Transplant 2009 Aug; 13(5): 571–8PubMedCrossRefGoogle Scholar
  64. 64.
    Lau KK, Haddad MN, Berg GM, et al. Rapid steroid discontinuation for pediatric renal transplantation: a single center experience. Pediatr Transplant 2007 Aug; 11(5): 504–10PubMedCrossRefGoogle Scholar
  65. 65.
    Schwartz JJ, Ishitani MB, Weckwerth J, et al. Decreased incidence of acute rejection in adolescent kidney transplant recipients using antithymocyte induction and triple immunosuppression. Transplantation 2007 Sep 27; 84(6): 715–21PubMedCrossRefGoogle Scholar
  66. 66.
    Roche Pharmaceuticals. Zenapax® (daclizumab) sterile concentrate for injection: prescribing information [online]. Available from URL: http://www.fda.gov/cder/foi/label/2005/103749s5059lbl.pdf [Accessed 2009 Apr 19]
  67. 67.
    Mariat C, Alamartine E, Diab N, et al. A randomized prospective study comparing low-dose OKT3 to low-dose ATG for the treatment of acute steroid-resistant rejection episodes in kidney transplant recipients. Transpl Int 1998; 11(3): 231–6PubMedGoogle Scholar
  68. 68.
    Bustami RT, Ojo AO, Wolfe RA, et al. Immunosuppression and the risk of post-transplant malignancy among cadaveric first kidney transplant recipients. Am J Transplant 2004 Jan; 4(1): 87–93PubMedCrossRefGoogle Scholar
  69. 69.
    Dharnidharka VR, Stevens G. Risk for post-transplant lymphoproliferative disorder after polyclonal antibody induction in kidney transplantation. Pediatr Transplant 2005 Oct; 9(5): 622–6PubMedCrossRefGoogle Scholar
  70. 70.
    Caillard S, Dharnidharka V, Agodoa L, et al. Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation 2005 Nov 15; 80(9): 1233–43PubMedCrossRefGoogle Scholar
  71. 71.
    Marchetti P. New-onset diabetes after transplantation. J Heart Lung Transplant 2004 May; 23 (5 Suppl.): S194–201PubMedCrossRefGoogle Scholar
  72. 72.
    Breza J, Navrátil P. Renal transplantation in adults. BJU Int 1999 Jul; 84(2): 216–23PubMedCrossRefGoogle Scholar
  73. 73.
    Srinivas TR, Meier-Kriesche HU. Minimizing immunosuppression, an alternative approach to reducing side effects: objectives and interim result. Clin J Am Soc Nephrol 2008 Mar; 3 Suppl. 2: S101–16PubMedCrossRefGoogle Scholar
  74. 74.
    Vincenti F. Current use and future trends in induction therapy. Saudi J Kidney Dis Transpl 2005 Oct–Dec; 16(4): 506–13PubMedGoogle Scholar
  75. 75.
    European Renal Association and European Dialysis and Transplant Association. Section III: the transplant recipient from initial transplant hospitalization to 1 year post transplant. Nephrol Dial Transplant 2000; 15 Suppl. 7: 52–85CrossRefGoogle Scholar
  76. 76.
    European Association of Urology. Guidelines on renal transplantation [online]. Available from URL: http://www.uroweb.org/fileadmin/tx_eauguidelines/2009/Full/Renal_Transplant.pdf [Accessed 2009 Apr 6]
  77. 77.
    Augustine JJ, Hricik DE. Steroid sparing in kidney transplantation: changing paradigms, improving outcomes, and remaining questions. Clin J Am Soc Nephrol 2006 Sep; 1: 1080–9PubMedCrossRefGoogle Scholar
  78. 78.
    Hanaway M, Woodle ES, Mulgaonkar S, et al. 12 month results of a multicenter, randomized trial comparing three induction agents (alemtuzumab, thymoglobulin and basiliximab) with tacrolimus, mycophenolate mofetil and a rapid steroid withdrawal in renal transplantation [abstract no. 135]. Am J Transplant 2008 May; 8 (Suppl. 2): 215Google Scholar
  79. 79.
    Mulgaonkar S, Hanaway M, Woodle ES, et al. Continuing 24 month results of a multicenter, randomized trial comparing three induction agents (alemtuzumab, thymoglobulin and basiliximab) with tacrolimus, mycophenolate mofetil and a rapid steroid withdrawal in renal transplantation [abstract no 312]. Am J Transplant 2009 May; 9 Suppl. 2: 282Google Scholar
  80. 80.
    Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients (OPTN/SRTR). 2007 OPTN/SRTR annual Report: transplant data 1997–2006 [online]. Available from URL: http://www.ustransplant.org/annual_reports/current/default.htm [Accessed 2009 Apr 16]
  81. 81.
    Ortho Biotech Products Ltd. Orthoclone OKT® sterile solution (muromonab-CD3) for intravenous use only: prescribing information [online]. Available from URL: http://www.orthobiotech.com/orthobiotech/shared/OBI/PI/OKT3_PI.pdf [Accessed 2009 Apr 15]

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Wolters Kluwer Health ¦ AdisMairangi Bay, North Shore 0754, AucklandNew Zealand
  2. 2.Wolters Kluwer HealthPhiladelphiaUSA

Personalised recommendations