Skip to main content
SpringerLink
Log in

Current Concepts of Immunosuppression and Side Effects

  • Chapter
  • First Online:
Pathology of Solid Organ Transplantation

  • 1294 Accesses

Abstract

The first successful human solid organ transplant was a renal transplant between two identical twin siblings, on 23 Dec 1954 [103]. Given the monozygosity, essentially no immunosuppression was used. The recipient never had a rejection episode but died 8 years later from recurrent glomerulonephritis. The introduction of immunosuppression with prednisone, azathioprine, and occasionally antilymphocyte globulin (ALG) in the 1960s allowed successful nonidentical living donor and deceased donor transplants. Through the 1970s and early 1980s, 1-year survival rates and acute rejection rates were around 60%. In the mid-1980s, cyclosporine was introduced and rejection rates decreased to 40–50% and 1-year survival rates increased to 75–85%. In the last 2 decades with the introduction of newer immunosuppressive induction agents such as basiliximab, daclizumab, and thymoglobulin and maintenance agents including tacrolimus, mycophenolate, and sirolimus, transplant patients are able to achieve 1 year graft survival rates in excess of 90% and acute rejection rates of 5–20%. Over the last several years, the focus of even newer immunosuppressive drugs regimens has included immunosuppression targeting the co-stimulatory pathways and avoiding toxicities associated with steroids and the calcineurin inhibitors cyclosporine and tacrolimus.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. Transplantation 61(7), 1029–1037 (1996)

    Google Scholar 

  2. Aboujaoude, W., Milgrom, M.L., Govani, M.V.: Lymphedema associated with sirolimus in renal transplant recipients. Transplantation 77(7), 1094–1096 (2004)

    Article  PubMed  Google Scholar 

  3. Abramowicz, D., Goldman, M., De Pauw, L., et al.: The long-term effects of prophylactic OKT3 monoclonal antibody in cadaver kidney transplantation–a single-center, prospective, randomized study. Transplantation 54(3), 433–437 (1992)

    Article  CAS  PubMed  Google Scholar 

  4. Abramowicz, D., Pradier, O., Marchant, A., et al.: Induction of thromboses within renal grafts by high-dose prophylactic OKT3. Lancet 339(8796), 777–778 (1992)

    Article  CAS  PubMed  Google Scholar 

  5. Agha, I.A., Rueda, J., Alvarez, A., et al.: Short course induction immunosuppression with thymoglobulin for renal transplant recipients. Transplantation 73(3), 473–475 (2002)

    Article  CAS  PubMed  Google Scholar 

  6. Ahsan, N., Hricik, D., Matas, A., et al.: Prednisone withdrawal in kidney transplant recipients on cyclosporine and mycophenolate mofetil–a prospective randomized study. Steroid Withdrawal Study Group. Transplantation 68(12), 1865–1874 (1999)

    Article  CAS  PubMed  Google Scholar 

  7. Ahsan, N., Johnson, C., Gonwa, T., et al.: Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years. Transplantation 72(2), 245–250 (2001)

    Article  CAS  PubMed  Google Scholar 

  8. Alinari, L., Lapalombella, R., Andritsos, L., et al.: Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia. Oncogene 26(25), 3644–3653 (2007)

    Article  CAS  PubMed  Google Scholar 

  9. Allison, A.C.: Mechanisms of action of mycophenolate mofetil. Lupus 14(Suppl 1), s2–s8 (2005)

    Article  CAS  PubMed  Google Scholar 

  10. Baan, C.C., van Riemsdijk-Overbeeke, I.C., Boelaars-van Haperen, M.J., IJ, J.M., Weimar, W.: Inhibition of the IL-15 pathway in anti-CD25 mAb treated renal allograft recipients. Transpl. Immunol. 10(1), 81–87 (2002)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Bechstein, W.O.: Neurotoxicity of calcineurin inhibitors: impact and clinical management. Transpl. Int. 13(5), 313–326 (2000)

    Article  CAS  PubMed  Google Scholar 

  13. Bigaud, M., Wieczorek, G., Preussing, E., et al.: NVP-AEB071 (AEB), the novel oral inhibitor of protein kinase C (PKC) and early T-cell activation, prolongs non-human primates (NPH) kidney allograft survival when combined with everolimus (RAD), ERL080 (ERL) or FTY720 (FTY) without calcineurin inhibitor (CNI). Am. J. Transplant. 6(Suppl 2), 251 (2006)

    Google Scholar 

  14. Borie, D.C., Changelian, P.S., Larson, M.J., et al.: Immunosuppression by the JAK3 inhibitor CP-690, 550 delays rejection and significantly prolongs kidney allograft survival in nonhuman primates. Transplantation 79(7), 791–801 (2005)

    Article  CAS  PubMed  Google Scholar 

  15. Borie, D.C., Larson, M.J., Flores, M.G., et al.: Combined use of the JAK3 inhibitor CP-690, 550 with mycophenolate mofetil to prevent kidney allograft rejection in nonhuman primates. Transplantation 80(12), 1756–1764 (2005)

    Article  CAS  PubMed  Google Scholar 

  16. Brennan, D.C., Daller, J.A., Lake, K.D., Cibrik, D., Del Castillo, D.: Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J. Med. 355(19), 1967–1977 (2006)

    Article  CAS  PubMed  Google Scholar 

  17. Brennan, D.C., Flavin, K., Lowell, J.A., et al.: A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation 67(7), 1011–1018 (1999)

    Article  CAS  PubMed  Google Scholar 

  18. Briggs, D., Dudley, C., Pattison, J., et al.: Effects of immediate switch from cyclosporine microemulsion to tacrolimus at first acute rejection in renal allograft recipients. Transplantation 75(12), 2058–2063 (2003)

    Article  CAS  PubMed  Google Scholar 

  19. Budde, K., Glander, P., Kramer, B.K., et al.: Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in maintenance renal transplant recipients receiving tacrolimus: clinical, pharmacokinetic, and pharmacodynamic outcomes. Transplantation 83(4), 417–424 (2007)

    Article  PubMed  Google Scholar 

  20. Bunnapradist, S., Takemoto, S.K.: Multivariate analyses of antibody induction therapies. Clin. Transpl. 405–417 (2003)

    Google Scholar 

  21. Caillard, S., Dharnidharka, V., Agodoa, L., Bohen, E., Abbott, K.: Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation 80(9), 1233–1243 (2005)

    Article  CAS  PubMed  Google Scholar 

  22. Caillat-Zucman, S., Blumenfeld, N., Legendre, C., et al.: The OKT3 immunosuppressive effect. In situ antigenic modulation of human graft-infiltrating T cells. Transplantation 49(1), 156–160 (1990)

    Article  CAS  PubMed  Google Scholar 

  23. Campistol, J.M., Sacks, S.H.: Mechanisms of nephrotoxicity. Transplantation 69(12), SS5–SS10 (2000)

    CAS  PubMed  Google Scholar 

  24. Canzanello, V.J., Textor, S.C., Taler, S.J., et al.: Renal sodium handling with cyclosporin A and FK506 after orthotopic liver transplantation. J. Am. Soc. Nephrol. 5(11), 1910–1917 (1995)

    CAS  PubMed  Google Scholar 

  25. Carl, S., Dorsam, J., Mandelbaum, A., Staehler, G., Wiesel, M.: Combining FK 506 and mycophenolate mofetil for the treatment of acute corticosteroid-resistant rejection following kidney transplantation: a new therapeutic concept. Transplant. Proc. 30(4), 1236–1237 (1998)

    Article  CAS  PubMed  Google Scholar 

  26. Changelian, P.S., Flanagan, M.E., Ball, D.J., et al.: Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 302(5646), 875–878 (2003)

    Article  CAS  PubMed  Google Scholar 

  27. Chapman, T.M., Keating, G.M.: Basiliximab: a review of its use as induction therapy in renal transplantation. Drugs 63(24), 2803–2835 (2003)

    Article  CAS  PubMed  Google Scholar 

  28. Charpentier, B., Groth, C.G., Backman, L., et al.: Bicetre hospital experience with sirolimus-based therapy in human renal transplantation: the Sirolimus European Renal Transplant Study. Transplant. Proc. 35(3 Suppl), 58S–61S (2003)

    Article  CAS  PubMed  Google Scholar 

  29. Chatenoud, L.: Immunologic monitoring during OKT3 therapy. Clin. Transpl. 7(4 Pt 2), 422–430 (1993)

    CAS  Google Scholar 

  30. Cherikh, W.S., Kauffman, H.M., McBride, M.A., et al.: Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation. Transplantation 76(9), 1289–1293 (2003)

    Article  CAS  PubMed  Google Scholar 

  31. Claesson, K., Mayer, A.D., Squifflet, J.P., et al.: Lipoprotein patterns in renal transplant patients: a comparison between FK 506 and cyclosporine A patients. Transplant. Proc. 30(4), 1292–1294 (1998)

    Article  CAS  PubMed  Google Scholar 

  32. Cole, E., Landsberg, D., Russell, D., et al.: A pilot study of steroid-free immunosuppression in the prevention of acute rejection in renal allograft recipients. Transplantation 72(5), 845–850 (2001)

    Article  CAS  PubMed  Google Scholar 

  33. Conklyn, M., Andresen, C., Changelian, P., Kudlacz, E.: The JAK3 inhibitor CP-690550 selectively reduces NK and CD8+ cell numbers in cynomolgus monkey blood following chronic oral dosing. J. Leukoc. Biol. 76(6), 1248–1255 (2004)

    Article  CAS  PubMed  Google Scholar 

  34. Costanzo, A., Peris, K., Talamonti, M., et al.: Long-term treatment of plaque psoriasis with efalizumab: an Italian experience. Br. J. Dermatol. 156(Suppl 2), 17–23 (2007)

    Article  CAS  PubMed  Google Scholar 

  35. Cremers, S., Schoemaker, R., Scholten, E., et al.: Characterizing the role of enterohepatic recycling in the interactions between mycophenolate mofetil and calcineurin inhibitors in renal transplant patients by pharmacokinetic modelling. Br. J. Clin. Pharmacol. 60(3), 249–256 (2005)

    Article  CAS  PubMed  Google Scholar 

  36. d’Apice, A.J., Becker, G.J., Kincaid-Smith, P., et al.: A prospective randomized trial of low-dose versus high-dose steroids in cadaveric renal transplantation. Transplantation 37(4), 373–377 (1984)

    Article  PubMed  Google Scholar 

  37. Dharnidharka, V.R., Sullivan, E.K., Stablein, D.M., Tejani, A.H., Harmon, W.E.: Risk factors for posttransplant lymphoproliferative disorder (PTLD) in pediatric kidney transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Transplantation 71(8), 1065–1068 (2001)

    Article  CAS  PubMed  Google Scholar 

  38. Di Paolo, S., Teutonico, A., Leogrande, D., Capobianco, C., Schena, P.F.: Chronic inhibition of mammalian target of rapamycin signaling downregulates insulin receptor substrates 1 and 2 and AKT activation: A crossroad between cancer and diabetes? J. Am. Soc. Nephrol. 17(8), 2236–2244 (2006)

    Article  PubMed  CAS  Google Scholar 

  39. Dumont, F.J., Su, Q.: Mechanism of action of the immunosuppressant rapamycin. Life Sci. 58(5), 373–395 (1996)

    Article  CAS  PubMed  Google Scholar 

  40. Fecteau, S., Basadonna, G.P., Freitas, A., et al.: CTLA-4 up-regulation plays a role in tolerance mediated by CD45. Nat. Immunol. 2(1), 58–63 (2001)

    Article  CAS  PubMed  Google Scholar 

  41. Flechner, S.M., Goldfarb, D., Modlin, C., et al.: Kidney transplantation without calcineurin inhibitor drugs: a prospective, randomized trial of sirolimus versus cyclosporine. Transplantation 74(8), 1070–1076 (2002)

    Article  CAS  PubMed  Google Scholar 

  42. Frampton, J.E., Wagstaff, A.J.: Alemtuzumab. Drugs 63(12), 1229–1243 (2003). discussion 1245–1226

    Article  CAS  PubMed  Google Scholar 

  43. Franz, M., Regele, H., Schmaldienst, S., et al.: Posttransplant hemolytic uremic syndrome in adult retransplanted kidney graft recipients: advantage of FK506 therapy? Transplantation 66(9), 1258–1262 (1998)

    Article  CAS  PubMed  Google Scholar 

  44. Friend, P., Russ, G., Oberbauer, R., et al.: Incidence of anemia in sirolimus-treated renal transplant recipients: the importance of preserving renal function. Transpl. Int. 20(9), 754–760 (2007)

    Article  CAS  PubMed  Google Scholar 

  45. Gaber, A.O., First, M.R., Tesi, R.J., 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 66(1), 29–37 (1998)

    Article  CAS  PubMed  Google Scholar 

  46. Gaston, R.S.: Maintenance immunosuppression in the renal transplant recipient: an overview. Am. J. Kidney Dis. 38(6 Suppl 6), S25–S35 (2001)

    Article  CAS  PubMed  Google Scholar 

  47. Giessing, M., Budde, K.: Sirolimus and lymphocele formation after kidney transplantation: an immunosuppressive medication as co-factor for a surgical problem? Nephrol. Dial. Transplant. 18(2), 448–449 (2003)

    Article  PubMed  Google Scholar 

  48. Gregory, C.R., Huie, P., Billingham, M.E., Morris, R.E.: Rapamycin inhibits arterial intimal thickening caused by both alloimmune and mechanical injury. Its effect on cellular, growth factor, and cytokine response in injured vessels. Transplantation 55(6), 1409–1418 (1993)

    Article  CAS  PubMed  Google Scholar 

  49. Gross, D., Belingheri, M., Vincenti, F., Bluestone, J.: Enhanced regulatory T-cell infiltration of renal allografts in the presence of costimulation blockade with belatacept. Am. J. Transplant. 6(Suppl 2), 375 (2006)

    Google Scholar 

  50. Groth, C.G., Backman, L., Morales, J.M., et al.: Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group. Transplantation 67(7), 1036–1042 (1999)

    Article  CAS  PubMed  Google Scholar 

  51. Hardinger, K.L., Schnitzler, M.A., Miller, B., et al.: Five-year follow up of thymoglobulin versus ATGAM induction in adult renal transplantation. Transplantation 78(1), 136–141 (2004)

    Article  CAS  PubMed  Google Scholar 

  52. Hricik, D.E.: Use of sirolimus to facilitate cyclosporine avoidance or steroid withdrawal in kidney transplant recipients. Transplant. Proc. 35(3 Suppl), 73S–78S (2003)

    Article  CAS  PubMed  Google Scholar 

  53. Hricik, D.E., O’Toole, M.A., Schulak, J.A., Herson, J.: Steroid-free immunosuppression in cyclosporine-treated renal transplant recipients: a meta-analysis. J. Am. Soc. Nephrol. 4(6), 1300–1305 (1993)

    CAS  PubMed  Google Scholar 

  54. Huang, S., Bjornsti, M.A., Houghton, P.J.: Rapamycins: mechanism of action and cellular resistance. Cancer Biol. Ther. 2(3), 222–232 (2003)

    CAS  PubMed  Google Scholar 

  55. Jaber, J.J., Feustel, P.J., Elbahloul, O., et al.: Early steroid withdrawal therapy in renal transplant recipients: a steroid-free sirolimus and Cell Cept-based calcineurin inhibitor-minimization protocol. Clin. Transpl. 21(1), 101–109 (2007)

    Article  Google Scholar 

  56. Jaffers, G.J., Fuller, T.C., Cosimi, A.B., et al.: Monoclonal antibody therapy. Anti-idiotypic and non-anti-idiotypic antibodies to OKT3 arising despite intense immunosuppression. Transplantation 41(5), 572–578 (1986)

    Article  CAS  PubMed  Google Scholar 

  57. Jensik, S.C.: Tacrolimus (FK 506) in kidney transplantation: three-year survival results of the US multicenter, randomized, comparative trial. FK 506 Kidney Transplant Study Group. Transplant. Proc. 30(4), 1216–1218 (1998)

    Article  CAS  PubMed  Google Scholar 

  58. Johnson, C., Ahsan, N., Gonwa, T., et al.: Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation. Transplantation 69(5), 834–841 (2000)

    Article  CAS  PubMed  Google Scholar 

  59. Kaden, J., May, G., Schonemann, C., et al.: Effect of ATG prophylaxis in sensitized and non-sensitized kidney graft recipients. Transpl. Int. 5(Suppl 1), S75–S78 (1992)

    PubMed  Google Scholar 

  60. Kahan, B.D.: Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study. The Rapamune US Study Group. Lancet 356(9225), 194–202 (2000)

    Article  CAS  PubMed  Google Scholar 

  61. Kahan, B.D., Julian, B.A., Pescovitz, M.D., Vanrenterghem, Y., Neylan, J.: Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group. Transplantation 68(10), 1526–1532 (1999)

    Article  CAS  PubMed  Google Scholar 

  62. Kahan, B.D., Rajagopalan, P.R., Hall, M.: Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. United States Simulect Renal Study Group. Transplantation 67(2), 276–284 (1999)

    Article  CAS  PubMed  Google Scholar 

  63. Kaplan, B., Meier-Kriesche, H.U., Jacobs, M.G., et al.: Prevalence of cytomegalovirus in the gastrointestinal tract of renal transplant recipients with persistent abdominal pain. Am. J. Kidney Dis. 34(1), 65–68 (1999)

    Article  CAS  PubMed  Google Scholar 

  64. Kasiske, B.L., Chakkera, H.A., Louis, T.A., Ma, J.Z.: A meta-analysis of immunosuppression withdrawal trials in renal transplantation. J. Am. Soc. Nephrol. 11(10), 1910–1917 (2000)

    CAS  PubMed  Google Scholar 

  65. Kasiske, B.L., Snyder, J.J., Gilbertson, D., Matas, A.J.: Diabetes mellitus after kidney transplantation in the United States. Am. J. Transplant. 3(2), 178–185 (2003)

    Article  PubMed  Google Scholar 

  66. Kim, M.J., Mayr, M., Pechula, M., Steiger, J., Dickenmann, M.: Marked erythrocyte microcytosis under primary immunosuppression with sirolimus. Transpl. Int. 19(1), 12–18 (2006)

    Article  CAS  PubMed  Google Scholar 

  67. Kirby, J.A., Lin, Y., Browell, D.A., et al.: Renal allograft rejection: examination of adhesion blockade by antilymphocyte antibody drugs. Nephrol. Dial. Transplant. 8(6), 544–550 (1993)

    CAS  PubMed  Google Scholar 

  68. Kirk, A.D.: Induction immunosuppression. Transplantation 82(5), 593–602 (2006)

    Article  PubMed  Google Scholar 

  69. Kirk, A.D., Hale, D.A., Swanson, S.J., Mannon, R.B.: Autoimmune thyroid disease after renal transplantation using depletional induction with alemtuzumab. Am. J. Transplant. 6(5 Pt 1), 1084–1085 (2006)

    Article  CAS  PubMed  Google Scholar 

  70. Knechtle, S.J., Fernandez, L.A., Pirsch, J.D., et al.: Campath-1H in renal transplantation: The University of Wisconsin experience. Surgery 136(4), 754–760 (2004)

    Article  PubMed  Google Scholar 

  71. Kudlacz, E., Perry, B., Sawyer, P., et al.: The novel JAK-3 inhibitor CP-690550 is a potent immunosuppressive agent in various murine models. Am. J. Transplant. 4(1), 51–57 (2004)

    Article  CAS  PubMed  Google Scholar 

  72. Kung, L., Halloran, P.F.: Immunophilins may limit calcineurin inhibition by cyclosporine and tacrolimus at high drug concentrations. Transplantation 70(2), 327–335 (2000)

    Article  CAS  PubMed  Google Scholar 

  73. Lai, J.H., Tan, T.H.: CD28 signaling causes a sustained down-regulation of I kappa B alpha which can be prevented by the immunosuppressant rapamycin. J. Biol. Chem. 269(48), 30077–30080 (1994)

    CAS  PubMed  Google Scholar 

  74. Larsen, J.L., Bennett, R.G., Burkman, T., et al.: Tacrolimus and sirolimus cause insulin resistance in normal sprague dawley rats. Transplantation 82(4), 466–470 (2006)

    Article  CAS  PubMed  Google Scholar 

  75. Larsen, C.P., Knechtle, S.J., Adams, A., Pearson, T., Kirk, A.D.: A new look at blockade of T-cell costimulation: a therapeutic strategy for long-term maintenance immunosuppression. Am. J. Transplant. 6(5 Pt 1), 876–883 (2006)

    Article  CAS  PubMed  Google Scholar 

  76. Larsen, C.P., Pearson, T.C., Adams, A.B., et al.: Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am. J. Transplant. 5(3), 443–453 (2005)

    Article  CAS  PubMed  Google Scholar 

  77. Lawen, J.G., Davies, E.A., Mourad, G., et al.: Randomized double-blind study of immunoprophylaxis with basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, in combination with mycophenolate mofetil-containing triple therapy in renal transplantation. Transplantation 75(1), 37–43 (2003)

    Article  CAS  PubMed  Google Scholar 

  78. Lebranchu, Y., Bridoux, F., Buchler, M., et al.: Immunoprophylaxis with basiliximab compared with antithymocyte globulin in renal transplant patients receiving MMF-containing triple therapy. Am. J. Transplant. 2(1), 48–56 (2002)

    Article  CAS  PubMed  Google Scholar 

  79. Lebwohl, M., Tyring, S.K., Hamilton, T.K., et al.: A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J. Med. 349(21), 2004–2013 (2003)

    Article  CAS  PubMed  Google Scholar 

  80. Lee, P., Lou, H., Vathsala, A.: Clinical pharmacokinetics of sirolimus in renal transplant recipients on maintenance sirolimus-based therapy. Transplantation 82(1)(Suppl 3), 520 (2006)

    Google Scholar 

  81. Letavernier, E., Bruneval, P., Mandet, C., et al.: High sirolimus levels may induce focal segmental glomerulosclerosis de novo. Clin. J. Am. Soc. Nephrol. 2(2), 326–333 (2007)

    Article  CAS  PubMed  Google Scholar 

  82. Liapis, H., Storch, G.A., Hill, D.A., Rueda, J., Brennan, D.C.: CMV infection of the renal allograft is much more common than the pathology indicates: a retrospective analysis of qualitative and quantitative buffy coat CMV-PCR, renal biopsy pathology and tissue CMV-PCR. Nephrol. Dial. Transplant. 18(2), 397–402 (2003)

    Article  PubMed  Google Scholar 

  83. Ligtenberg, G., Hene, R.J., Blankestijn, P.J., Koomans, H.A.: Cardiovascular risk factors in renal transplant patients: cyclosporin A versus tacrolimus. J. Am. Soc. Nephrol. 12(2), 368–373 (2001)

    CAS  PubMed  Google Scholar 

  84. Lin, M., Ming, A., Zhao, M.: Two-dose basiliximab compared with two-dose daclizumab in renal transplantation: a clinical study. Clin. Transpl. 20(3), 325–329 (2006)

    Article  Google Scholar 

  85. Lindenfeld, J., Miller, G.G., Shakar, S.F., et al.: Drug therapy in the heart transplant recipient: part II: immunosuppressive drugs. Circulation 110(25), 3858–3865 (2004)

    Article  CAS  PubMed  Google Scholar 

  86. Lopez, M., Clarkson, M.R., Albin, M., Sayegh, M.H., Najafian, N.: A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells. J. Am. Soc. Nephrol. 17(10), 2844–2853 (2006)

    Article  CAS  PubMed  Google Scholar 

  87. Macchi, P., Villa, A., Giliani, S., et al.: Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature 377(6544), 65–68 (1995)

    Article  CAS  PubMed  Google Scholar 

  88. Machado, P.G., Felipe, C.R., Hanzawa, N.M., et al.: An open-label randomized trial of the safety and efficacy of sirolimus vs. azathioprine in living related renal allograft recipients receiving cyclosporine and prednisone combination. Clin. Transpl. 18(1), 28–38 (2004)

    Article  Google Scholar 

  89. Mahalati, K., Kahan, B.D.: A pilot study of steroid withdrawal from kidney transplant recipients on sirolimus-cyclosporine a combination therapy. Transplant. Proc. 33(7–8), 3232–3233 (2001)

    Article  CAS  PubMed  Google Scholar 

  90. Maiorano, A., Stallone, G., Schena, A., et al.: Sirolimus interferes with iron homeostasis in renal transplant recipients. Transplantation 82(7), 908–912 (2006)

    Article  CAS  PubMed  Google Scholar 

  91. Marcen, R., Pascual, J., Teruel, J.L., et al.: Outcome of cadaveric renal transplant patients treated for 10 years with cyclosporine: is chronic allograft nephropathy the major cause of late graft loss? Transplantation 72(1), 57–62 (2001)

    Article  CAS  PubMed  Google Scholar 

  92. Margreiter, R.: Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study. Lancet 359(9308), 741–746 (2002)

    Article  CAS  PubMed  Google Scholar 

  93. Marvin, M.R., Droogan, C., Sawinski, D., Cohen, D.J., Hardy, M.A.: Administration of rabbit antithymocyte globulin (thymoglobulin) in ambulatory renal-transplant patients. Transplantation 75(4), 488–489 (2003)

    Article  CAS  PubMed  Google Scholar 

  94. Mayer, A.D., Dmitrewski, J., Squifflet, J.P., et al.: Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. Transplantation 64(3), 436–443 (1997)

    Article  CAS  PubMed  Google Scholar 

  95. McTaggart, R.A., Gottlieb, D., Brooks, J., et al.: Sirolimus prolongs recovery from delayed graft function after cadaveric renal transplantation. Am. J. Transplant. 3(4), 416–423 (2003)

    Article  CAS  PubMed  Google Scholar 

  96. Menter, A., Gordon, K., Carey, W., et al.: Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis. Arch. Dermatol. 141(1), 31–38 (2005)

    Article  CAS  PubMed  Google Scholar 

  97. Merville, P., Berge, F., Deminiere, C., et al.: Lower incidence of chronic allograft nephropathy at 1 year post-transplantation in patients treated with mycophenolate mofetil. Am. J. Transplant. 4(11), 1769–1775 (2004)

    Article  CAS  PubMed  Google Scholar 

  98. Mihatsch, M.J., Kyo, M., Morozumi, K., et al.: The side-effects of ciclosporine-A and tacrolimus. Clin. Nephrol. 49(6), 356–363 (1998)

    CAS  PubMed  Google Scholar 

  99. Miura, M., Harada, H., Fukuzawa, N., et al.: Quadruple immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil and prednisone is safe and effective for renal transplantation. Clin. Transpl. 19(Suppl 14), 54–58 (2005)

    Article  Google Scholar 

  100. Morelon, E., Kreis, H.: Sirolimus therapy without calcineurin inhibitors: Necker Hospital 8-year experience. Transplant. Proc. 35(3 Suppl), 52S–57S (2003)

    Article  CAS  PubMed  Google Scholar 

  101. Morris, P.J., Chan, L., French, M.E., Ting, A.: Low dose oral prednisolone in renal transplantation. Lancet 1(8271), 525–527 (1982)

    Article  CAS  PubMed  Google Scholar 

  102. 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 78(4), 584–590 (2004)

    Article  CAS  PubMed  Google Scholar 

  103. Murray, J.E., Merrill, J.P., Harrison, J.H.: Renal homotransplantation in identical twins. 1955. J. Am. Soc. Nephrol. 12(1), 201–204 (2001)

    CAS  PubMed  Google Scholar 

  104. Mycophenolate mofetil for the treatment of refractory, acute, cellular renal transplant rejection. The Mycophenolate Mofetil Renal Refractory Rejection Study Group. Transplantation 61(5), 722–729 (1996)

    Google Scholar 

  105. Nampoory, M.R., Abdulhalim, M., Johny, K.V., et al.: Bolus anti-thymocyte globulin induction in renal transplant recipients: a comparison with conventional ATG or anti-interleukin-2 receptor antibody induction. Transplant. Proc. 34(7), 2916–2919 (2002)

    Article  CAS  PubMed  Google Scholar 

  106. Nankivell, B.J., Borrows, R.J., Fung, C.L., et al.: The natural history of chronic allograft nephropathy. N Engl J. Med. 349(24), 2326–2333 (2003)

    Article  CAS  PubMed  Google Scholar 

  107. Nashan, B., Light, S., Hardie, I.R., Lin, A., Johnson, J.R.: Reduction of acute renal allograft rejection by daclizumab. Daclizumab Double Therapy Study Group. Transplantation 67(1), 110–115 (1999)

    Article  CAS  PubMed  Google Scholar 

  108. Nashan, B., Moore, R., Amlot, P., et al.: Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group. Lancet 350(9086), 1193–1198 (1997)

    Article  CAS  PubMed  Google Scholar 

  109. Norman, D.J., Kahana, L., Stuart Jr., F.P., et al.: A randomized clinical trial of induction therapy with OKT3 in kidney transplantation. Transplantation 55(1), 44–50 (1993)

    Article  CAS  PubMed  Google Scholar 

  110. Onrust, S.V., Wiseman, L.R.: Basiliximab. Drugs 57(2), 207–213 (1999). discussion 214

    Article  CAS  PubMed  Google Scholar 

  111. Opelz, G., Dohler, B.: Lymphomas after solid organ transplantation: a collaborative transplant study report. Am. J. Transplant. 4(2), 222–230 (2004)

    Article  PubMed  Google Scholar 

  112. Opelz, G., Dohler, B., Laux, G.: Long-term prospective study of steroid withdrawal in kidney and heart transplant recipients. Am. J. Transplant. 5(4 Pt 1), 720–728 (2005)

    Article  CAS  PubMed  Google Scholar 

  113. Paniagua, R., Si, M.S., Flores, M.G., et al.: Effects of JAK3 inhibition with CP-690, 550 on immune cell populations and their functions in nonhuman primate recipients of kidney allografts. Transplantation 80(9), 1283–1292 (2005)

    Article  CAS  PubMed  Google Scholar 

  114. Pham, K., Kraft, K., Thielke, J., et al.: Limited-dose Daclizumab versus Basiliximab: a comparison of cost and efficacy in preventing acute rejection. Transplant. Proc. 37(2), 899–902 (2005)

    Article  CAS  PubMed  Google Scholar 

  115. Pham, P.T., Pham, P.C., Danovitch, G.M., et al.: Sirolimus-associated pulmonary toxicity. Transplantation 77(8), 1215–1220 (2004)

    Article  CAS  PubMed  Google Scholar 

  116. Pirsch, J.D., Miller, J., Deierhoi, M.H., Vincenti, F., Filo, R.S.: A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group. Transplantation 63(7), 977–983 (1997)

    Article  CAS  PubMed  Google Scholar 

  117. Pittock, S.J., Rabinstein, A.A., Edwards, B.S., Wijdicks, E.F.: OKT3 neurotoxicity presenting as akinetic mutism. Transplantation 75(7), 1058–1060 (2003)

    Article  CAS  PubMed  Google Scholar 

  118. Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. European Mycophenolate Mofetil Cooperative Study Group. Lancet 345(8961), 1321–1325 (1995)

    Google Scholar 

  119. Ponticelli, C.: Cyclosporine: from renal transplantation to autoimmune diseases. Ann. N. Y. Acad. Sci. 1051, 551–558 (2005)

    Article  CAS  PubMed  Google Scholar 

  120. Ponticelli, C., Yussim, A., Cambi, V., et al.: A randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients. Transplantation 72(7), 1261–1267 (2001)

    Article  CAS  PubMed  Google Scholar 

  121. Pourfarziani, V., Lesanpezeshki, M., Einollahi, B., et al.: Zenapax versus ALG prophylaxis in immunologically high-risk group of renal allograft recipients. Nephrol. Dial. Transplant. 18(Suppl 4), 494 (2003)

    Google Scholar 

  122. Pradier, O., Marchant, A., Abramowicz, D., et al.: Procoagulant effect of the OKT3 monoclonal antibody: involvement of tumor necrosis factor. Kidney Int. 42(5), 1124–1129 (1992)

    Article  CAS  PubMed  Google Scholar 

  123. Rangan, G.K.: Sirolimus-associated proteinuria and renal dysfunction. Drug Saf. 29(12), 1153–1161 (2006)

    Article  CAS  PubMed  Google Scholar 

  124. Rebello, P., Cwynarski, K., Varughese, M., et al.: Pharmacokinetics of CAMPATH-1H in BMT patients. Cytotherapy 3(4), 261–267 (2001)

    Article  CAS  PubMed  Google Scholar 

  125. Remuzzi, G., Cravedi, P., Costantini, M., et al.: Mycophenolate mofetil versus azathioprine for prevention of chronic allograft dysfunction in renal transplantation: the MYSS follow-up randomized, controlled clinical trial. J. Am. Soc. Nephrol. 18(6), 1973–1985 (2007)

    Article  CAS  PubMed  Google Scholar 

  126. Remuzzi, G., Lesti, M., Gotti, E., et al.: Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial. Lancet 364(9433), 503–512 (2004)

    Article  CAS  PubMed  Google Scholar 

  127. Reynolds, J.C., Agodoa, L.Y., Yuan, C.M., Abbott, K.C.: Thrombotic microangiopathy after renal transplantation in the United States. Am. J. Kidney Dis. 42(5), 1058–1068 (2003)

    Article  PubMed  Google Scholar 

  128. Rosen, H.R., Shackleton, C.R., Higa, L., et al.: Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation. Am. J. Gastroenterol. 92(9), 1453–1457 (1997)

    CAS  PubMed  Google Scholar 

  129. Rostaing, L., Cantarovich, D., Mourad, G., et al.: Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation. Transplantation 79(7), 807–814 (2005)

    Article  CAS  PubMed  Google Scholar 

  130. Rostaing, L., Puyoo, O., Tkaczuk, J., et al.: Differences in Type 1 and Type 2 intracytoplasmic cytokines, detected by flow cytometry, according to immunosuppression (cyclosporine A vs. tacrolimus) in stable renal allograft recipients. Clin. Transpl. 13(5), 400–409 (1999)

    Article  CAS  Google Scholar 

  131. Rousvoal, G., Si, M.S., Lau, M., et al.: Janus kinase 3 inhibition with CP-690, 550 prevents allograft vasculopathy. Transpl. Int. 19(12), 1014–1021 (2006)

    Article  CAS  PubMed  Google Scholar 

  132. Sabbatini, M., Sansone, G., Uccello, F., et al.: Acute effects of rapamycin on glomerular dynamics: a micropuncture study in the rat. Transplantation 69(9), 1946–1990 (2000)

    Article  CAS  PubMed  Google Scholar 

  133. Shapiro, R., Jordan, M.L., Basu, A., et al.: Kidney transplantation under a tolerogenic regimen of recipient pretreatment and low-dose postoperative immunosuppression with subsequent weaning. Ann. Surg. 238(4), 520–525 (2003). discussion 525–527

    PubMed  Google Scholar 

  134. Sheashaa, H.A., Bakr, M.A., Ismail, A.M., et al.: Long-term evaluation of basiliximab induction therapy in live donor kidney transplantation: a five-year prospective randomized study. Am. J. Nephrol. 25(3), 221–225 (2005)

    Article  CAS  PubMed  Google Scholar 

  135. Shihab, F.S., Bennett, W.M., Yi, H., Choi, S.O., Andoh, T.F.: Sirolimus increases transforming growth factor-beta1 expression and potentiates chronic cyclosporine nephrotoxicity. Kidney Int. 65(4), 1262–1271 (2004)

    Article  CAS  PubMed  Google Scholar 

  136. Sidhu, M.S., Nayak, K.S., Subhramanyam, S.V., Sankar, A.: Polyclonal antibodies in renal transplantation–a relook. Transplant. Proc. 39(3), 766–772 (2007)

    Article  CAS  PubMed  Google Scholar 

  137. Simon, J.F., Swanson, S.J., Agodoa, L.Y., et al.: Induction sirolimus and delayed graft function after deceased donor kidney transplantation in the United States. Am. J. Nephrol. 24(4), 393–401 (2004)

    Article  CAS  PubMed  Google Scholar 

  138. Slade, A., Vitaliti, A., Agyemang, A., Sieberling, M., Schmouder, R.: NVP-AEB071: Human pharmacodynamics in combination with mycophenolic acid. Am. J. Transplant. 6(Suppl 2), 199 (2006)

    Google Scholar 

  139. Smith, J.M., Nemeth, T.L., McDonald, R.A.: Current immunosuppressive agents in pediatric renal transplantation: efficacy, side-effects and utilization. Pediatr. Transplant. 8(5), 445–453 (2004)

    Article  CAS  PubMed  Google Scholar 

  140. Solez, K., Vincenti, F., Filo, R.S.: Histopathologic findings from 2-year protocol biopsies from a U.S. multicenter kidney transplant trial comparing tarolimus versus cyclosporine: a report of the FK506 Kidney Transplant Study Group. Transplantation 66(12), 1736–1740 (1998)

    Article  CAS  PubMed  Google Scholar 

  141. Sollinger, H.W.: Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group. Transplantation 60(3), 225–232 (1995)

    Article  CAS  PubMed  Google Scholar 

  142. Sollinger, H., Kaplan, B., Pescovitz, M.D., et al.: Basiliximab versus antithymocyte globulin for prevention of acute renal allograft rejection. Transplantation 72(12), 1915–1919 (2001)

    Article  CAS  PubMed  Google Scholar 

  143. Stallone, G., Di Paolo, S., Schena, A., et al.: Addition of sirolimus to cyclosporine delays the recovery from delayed graft function but does not affect 1-year graft function. J. Am. Soc. Nephrol. 15(1), 228–233 (2004)

    Article  CAS  PubMed  Google Scholar 

  144. Stepkowski, S.M., Kirken, R.A.: Janus tyrosine kinases and signal transducers and activators of transcription regulate critical functions of T cells in allograft rejection and transplantation tolerance. Transplantation 82(3), 295–303 (2006)

    Article  CAS  PubMed  Google Scholar 

  145. Stratta, R.J., Alloway, R.R., Lo, A., Hodge, E.: Two-dose daclizumab regimen in simultaneous kidney-pancreas transplant recipients: primary endpoint analysis of a multicenter, randomized study. Transplantation 75(8), 1260–1266 (2003)

    Article  CAS  PubMed  Google Scholar 

  146. Tan, J., Yang, S., Wu, W.: Basiliximab (Simulect) reduces acute rejection among sensitized kidney allograft recipients. Transplant. Proc. 37(2), 903–905 (2005)

    Article  CAS  PubMed  Google Scholar 

  147. Tanabe, K.: Calcineurin inhibitors in renal transplantation: what is the best option? Drugs 63(15), 1535–1548 (2003)

    Article  CAS  PubMed  Google Scholar 

  148. Tanabe, K., Tokumoto, T., Ishikawa, N., et al.: Japanese single-center experience of kidney transplantation under tacrolimus immunosuppression. Transplant. Proc. 32(7), 1696–1699 (2000)

    Article  CAS  PubMed  Google Scholar 

  149. Taylor, A.L., Watson, C.J., Bradley, J.A.: Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy. Crit. Rev. Oncol. Hematol. 56(1), 23–46 (2005)

    Article  PubMed  Google Scholar 

  150. Tedesco Silva, H., Pinheiro Machado Jr., P., Rosso Felipe, C., Medina Pestana, J.O.: Immunotherapy for De Novo renal transplantation: what’s in the pipeline? Drugs 66(13), 1665–1684 (2006)

    Article  PubMed  Google Scholar 

  151. Tesi, R.J., Kano, J.M., Horn, H.R., Schroeder, T.: Thymoglobulin reverses acute renal allograft rejection better than ATGAM--a double-blinded randomized clinical trial. Transplant. Proc. 29(7A), 21S–23S (1997)

    Article  CAS  PubMed  Google Scholar 

  152. Tessmer, C.S., Magalhaes, L.V., Keitel, E., et al.: Conversion to sirolimus in renal transplant recipients with skin cancer. Transplantation 82(12), 1792–1793 (2006)

    Article  PubMed  Google Scholar 

  153. Theruvath, T.P., Saidman, S.L., Mauiyyedi, S., et al.: Control of antidonor antibody production with tacrolimus and mycophenolate mofetil in renal allograft recipients with chronic rejection. Transplantation 72(1), 77–83 (2001)

    Article  CAS  PubMed  Google Scholar 

  154. Thistlethwaite Jr., J.R., Stuart, J.K., Mayes, J.T., et al.: Complications and monitoring of OKT3 therapy. Am. J. Kidney Dis. 11(2), 112–119 (1988)

    PubMed  Google Scholar 

  155. van Hooff, J.P., van Duijnhoven, E.M., Christiaans, M.H.: Tacrolimus and glucose metabolism. Transplant. Proc. 31(7A), 49S–50S (1999)

    PubMed  Google Scholar 

  156. Verbsky, J.W., Randolph, D.A., Shornick, L.P., Chaplin, D.D.: Nonhematopoietic expression of Janus kinase 3 is required for efficient recruitment of Th2 lymphocytes and eosinophils in OVA-induced airway inflammation. J. Immunol. 168(5), 2475–2482 (2002)

    CAS  PubMed  Google Scholar 

  157. Vieira Jr., J.M., Noronha, I.L., Malheiros, D.M., Burdmann, E.A.: Cyclosporine-induced interstitial fibrosis and arteriolar TGF-beta expression with preserved renal blood flow. Transplantation 68(11), 1746–1753 (1999)

    Article  CAS  PubMed  Google Scholar 

  158. Vincenti, F., de Andres, A., Becker, T., et al.: Interleukin-2 receptor antagonist induction in modern immunosuppression regimens for renal transplant recipients. Transpl. Int. 19(6), 446–457 (2006)

    Article  CAS  PubMed  Google Scholar 

  159. 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. 338(3), 161–165 (1998)

    Article  CAS  PubMed  Google Scholar 

  160. Vincenti, F., Larsen, C., Durrbach, A., et al.: Costimulation blockade with belatacept in renal transplantation. N Engl J. Med. 353(8), 770–781 (2005)

    Article  CAS  PubMed  Google Scholar 

  161. Vincenti, F., Luggen, M.: T cell costimulation: a rational target in the therapeutic armamentarium for autoimmune diseases and transplantation. Annu. Rev. Med. 58, 347–358 (2007)

    Article  CAS  PubMed  Google Scholar 

  162. Vincenti, F., Mendez, R., Pescovitz, M., et al.: A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. Am. J. Transplant. 7(7), 1770–1777 (2007)

    Article  CAS  PubMed  Google Scholar 

  163. Vincenti, F., Monaco, A., Grinyo, J., Kinkhabwala, M., Roza, A.: Multicenter randomized prospective trial of steroid withdrawal in renal transplant recipients receiving basiliximab, cyclosporine microemulsion and mycophenolate mofetil. Am. J. Transplant. 3(3), 306–311 (2003)

    Article  CAS  PubMed  Google Scholar 

  164. Vincenti, F., Monaco, A., Grinyo, J., et al.: Rapid steroid withdrawal versus standard steroid therapy in patients treated with basiliximab, cyclosporine, and mycophenolate mofetil for the prevention of acute rejection in renal transplantation. Transplant. Proc. 33(1–2), 1011–1012 (2001)

    Article  CAS  PubMed  Google Scholar 

  165. Vincenti, F., Schena, F., Walker, R., et al.: Preliminary 3-month results comparing immunosuppressive regimens of enteric-coated mycophenolate sodium (EC-MPS) without steroids vs short-term use of steroids vs standard steroid treatment including basiliximab and neoral C-2 in de novo kidney recipients. Am. J. Transplant. 5(Suppl 11), 548 (2005)

    Google Scholar 

  166. Wagner, J., Evenou, J., Zenke, G., et al.: The first-in-class oral protein kinase C (PKC) inhibitor NVP-AEB071 (AEB) prolongs renal allograft survival in non-human primates (NPH) and suppresses lymphocyte proliferation at safe exposures in human proof-of-concept studies. Am. J. Transplant. 6(Suppl 2), 86 (2006)

    Google Scholar 

  167. Wahba, I.M., Bennett, W.M.: Increased vascular resistance and not salt retention characterizes cyclosporine A-induced hypertension: report in an anuric patient. Am. J. Transplant. 7(8), 2042–2046 (2007)

    Article  CAS  PubMed  Google Scholar 

  168. Waldmann, H., Hale, G.: CAMPATH: from concept to clinic. Philos. Trans. R. Soc. Lond. B Biol. Sci. 360(1461), 1707–1711 (2005)

    Article  CAS  PubMed  Google Scholar 

  169. Wang, K., Zhang, H., Li, Y., et al.: Safety of mycophenolate mofetil versus azathioprine in renal transplantation: a systematic review. Transplant. Proc. 36(7), 2068–2070 (2004)

    Article  CAS  PubMed  Google Scholar 

  170. Watson, C.J., Bradley, J.A., Friend, P.J., et al.: Alemtuzumab (CAMPATH 1H) induction therapy in cadaveric kidney transplantation–efficacy and safety at five years. Am. J. Transplant. 5(6), 1347–1353 (2005)

    Article  CAS  PubMed  Google Scholar 

  171. Webster, A.C., Playford, E.G., Higgins, G., Chapman, J.R., Craig, J.C.: Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials. Transplantation 77(2), 166–176 (2004)

    Article  CAS  PubMed  Google Scholar 

  172. Woodle, E.S., First, M.R., Pirsch, J., et al.: A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Ann. Surg. 248(4), 564–577 (2008)

    PubMed  Google Scholar 

  173. Woodle, E.S., Vincenti, F., Lorber, M.I., et al.: A multicenter pilot study of early (4-day) steroid cessation in renal transplant recipients under simulect, tacrolimus and sirolimus. Am. J. Transplant. 5(1), 157–166 (2005)

    Article  CAS  PubMed  Google Scholar 

  174. Yabu, J.M., Vincenti, F.: Novel immunosuppression: small molecules and biologics. Semin. Nephrol. 27(4), 479–486 (2007)

    Article  CAS  PubMed  Google Scholar 

  175. Zarifian, A., Meleg-Smith, S., O’Donovan, R., Tesi, R.J., Batuman, V.: Cyclosporine-associated thrombotic microangiopathy in renal allografts. Kidney Int. 55(6), 2457–2466 (1999)

    Article  CAS  PubMed  Google Scholar 

  176. Zietse, R., van Steenberge, E.P., Hesse, C.J., et al.: Single-shot, high-dose rabbit ATG for rejection prophylaxis after kidney transplantation. Transpl. Int. 6(6), 337–340 (1993)

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Washington University in St. Louis, 4104 Queeny Tower, One Barnes-Jewish Hospital Plaza, St. Louis, MO, 63110, USA

    Anand Khurana & Daniel C. Brennan

Authors
  1. Anand Khurana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel C. Brennan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel C. Brennan .

Editor information

Editors and Affiliations

  1. School of Medicine, Dept. Pathology & Immunology, Washington University, S. Euclid Ave. 660, St.Louis, 63110, Missouri, USA

    Helen Liapis

  2. , Dept. of Pathology, Cedars-Sinai Medical Center, Beverly Blvd. 8700, Los Angeles, 90048, California, USA

    Hanlin L. Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Berlin Heidelberg

About this chapter

Cite this chapter

Khurana, A., Brennan, D.C. (2009). Current Concepts of Immunosuppression and Side Effects. In: Liapis, H., Wang, H. (eds) Pathology of Solid Organ Transplantation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-79343-4_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-79343-4_2

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-79342-7

  • Online ISBN: 978-3-540-79343-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation