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Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

2005, Number 2

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Rev Invest Clin 2005; 57 (2)

Immunosuppression for recipients of renal transplant: actual strategies

Alberú J, Mancilla-Urrea E

Language: Spanish
References: 81
Page: 213-224
PDF size: 103.72 Kb.


ABSTRACT

Immunosuppressive therapy aims to protect transplanted organs from host responses. The success achieved during the last two decades in patient and graft survival is mainly related to the development and clinical use of efficacious immunosuppressive drugs. Nevertheless, the challenge of achieving a balance of adequate graft protection while minimizing the adverse consequences of excessive immunosuppression in the long-term continues. Current maintenance immunosuppression for renal transplant recipients generally consists of a calcineurin inhibitor plus an adjunctive antiproliferative agent, and steroids. The addition of induction therapy with a variety of monoclonal or polyclonal antibodies provides a more potent immunosuppression and its use is more relevant in patients with a high immunological risk. More recently, mammalian target of rapamycin inhibitors have been incorporated in different schemes proven its efficacy in a number of protocols. The incidence of acute rejection is now in its lower historical percentage and excellent results are reported from many transplant centers all over the world due mainly to a judicious combination of these drugs evaluated through many clinical studies. However, long-term use of immunosuppressive drugs convey inherent risks which translate in an increase of cancers and infections, among others. Ongoing investigations and clinical protocols involving new immunosuppressive drugs and biological agents are yielding important information on how to obtain tolerance or the nearest to this goal. Furthermore, there should be a continuous improvement in patient and graft survival, as the use of different immunosuppressive agents for induction and maintenance are individualized (adapted to each patient).


REFERENCES

  1. Harrison JH, Merrill JP, Murray JE. Renal homotransplantations in identical twins. Surg Forum 1956; 6: 432-6.

  2. Merion RM, White DJG, Thiru S, Evans DB, Calne RY. Cyclosporine: five-years experience in cadaveric renal transplantation. N Engl J Med 1984; 310: 148-54.

  3. Cecka JM. The UNOS scientific renal transplant registry. In: Cecka JM, Terasaki PI (Eds.) Clinical transplants. Los Angeles: UCLA Tissue Typing Laboratory; 1996, p.1-14.

  4. Sollinger HW. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Transplantation 1995; 60: 225-32.

  5. Pirsch JD, Miller J, Deierhoi MH, Vincenti F, Filo RS. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. Transplantation 1997; 63: 977-83.

  6. Hariharan S, Johnson CP, Bresnahan BA, et al. Improved graft survival after renal transplantation in the United States, 1988-96. N Engl J Med 2000; 342: 605-12.

  7. Sayegh M, Watschinger B, Carpenter C. Mechanisms of T cell recognition on alloantigen: the role of peptides. Transplantation 1994; 57: 1295-302.

  8. Sayegh M, Turka L. The role of T cell co-stimulatory activation pathways in transplant rejection. N Engl J Med 1998; 338: 1813-21.

  9. Kahan B. Cyclosporin. N Engl J Med 1989; 321: 1725-38.

  10. Bennet W, Dem Mattos A, Meyer M, Andoh T, Barry J. Chronic cyclosporine nephropathy: the Achilles´ heel of immunosuppressive therapy. Kidney Int 1996; 50: 1089-100.

  11. Shin G, Khanna A, Ding R, et al. In vivo expression of transforming growth factor-b 1 in humans: stimulation by cyclosporine. Transplantation 1998; 65:313-18.

  12. Otto MG, Mayer AD, Clarien PA, et al. Randomized trial of cyclosporine micro-emulsion (Neoral) vs. conventional cyclosporine in liver transplantation: MILTON study. Multicenter International Study in Liver Transplantation of Neoral. Transplantation 1998; 66: 1623-40.

  13. First MR, Alloway R, Schroeder TJ. Development of Sang-35: a cyclosporine formulation bioequivalent to Neoral. Clin Transplant 1988; 12: 518-24.

  14. Kolars JC, Merion RM, Awni WM, Watkins PB. First-pass metabolism of cyclosporine by the gut. Lancet 1991; 338: 1488-90.

  15. Mueller EA, Kovarik JM, Van Bree JB, et al. Pharmacokinetics and tolerability of a micro-emulsion formulation of cyclosporine in renal allograft recipients: a concentration-controlled comparison with the commercial formulation. Transplantation 1994; 57: 1178.

  16. Kovarik JM, Mueller EA, Van Bree JB, et al. Within day consistency in cyclosporine pharmacokinetics from a micro-emulsion formulation in renal transplant patients. Ther Drug Monit 1994; 16: 232-7.

  17. Kovarik JM, Mueller EA, Van Bree JB, et al. Cyclosporine pharmacokinetics and variability from a micro-emulsion formulation: multicenter investigation in kidney transplant patients. Transplantation 1994; 58: 1-5.

  18. Mueller EA, Kovarik JM, Van Bree JB, et al. Improved dose-linearity of cyclosporine pharmacokinetics from a micro-emulsion formulation. Pharmacol Res 1994; 11: 301-4.

  19. Min DI, Peery PJ, Chen HY, Hunsicker LG. Cyclosporine through concentrations in predicting allograft rejection and renal toxicity up to 12 months after renal transplantation. Pharmacotherapy 1998; 18(2): 282-7.

  20. Levy G, Thervet E, Lake J, Uchida K. Patient management by Neoral C(2) monitoring: an international consensus statement. Transplantation 2002; 73(9 suppl): S19-22.

  21. Kino T, Hatanaka H, Miyata S, et al. FK-506, a novel immunosuppressant isolated from a Streptomycin’s, II. Immunosuppressive effect of FK-506 in vitro. J Antibiotics 1987; 40: 1256-65.

  22. Ochiai T, Nagata M, Nakajima K, et al. Studies of the effects of FK506 on renal allografting in the beagle dog. Transplantation 1987; 44: 729-33.

  23. Kino T, Inamura N, Sakai F, et al. Effect of FK506 on human mixed lymphocyte reaction in vitro. Transplant Proc 1987; 19: 36-9.

  24. Todo S, Ueda Y, Demetris JA, et al. Immunosuppression of canine, monkeys and baboon allografts by FK506; with special reference to synergism with other drugs and to tolerance induction. Surgery 1988; 104: 239-49.

  25. Nickeleit V, Hirsch HH, Zeiler M y cols. BK-virus nephropathy in renal transplants: tubular necrosis, MHC-class II expression and rejection in a puzzling game. Nephrol Dial Transplant 2000; 15(3): 324-32.

  26. Agha I, Álvarez A, López-Rocafort L, et al. A prospective evaluation of BK virus infection in renal transplant recipients (abstr). Am J Transplant 2002; 2(suppl 3): 260

  27. Lipshutz GS, Flechner SM, Govani MV, Vincenti F. BK nephropathy in kidney transplant recipients treated with a calcineurin inhibitor-free immunosuppression regimen. Am J Transplant 2004; 4: 2132-4.

  28. Danovitch GM. Immunosuppressant-induced metabolic toxicities. Transplant Rev 2000; 14(2): 65-81.

  29. Behrens O, Kohlhaw K, Gunter H, et al. Detection of cyclosporine A in breast milk: is breast feeding contraindicated? Geburtshilfe Fraunenheikunde 1989; 49: 207-9.

  30. Kronbach T, Fisher V, Meyer UA. Cyclosporine metabolism in human liver: identification of a cytochrome P-450III gene family as the mayor cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin Pharmacol Ther 1988; 43: 630-5.

  31. 31-. Knoll GA, Bell RC. tacrolimus vs. cyclosporine for immunosuppression in renal transplantation: meta-analysis of randomized trials. BMJ 1999; 318(7191): 1104-7.

  32. Margreiter R. Efficacy and safety of tacrolimus compared with cyclosporine micro-emulsion in renal transplantation: a randomized multicenter study. Lancet 2002; 359(9308): 741-6.

  33. Vincenti F, Jensik SC, Filo RS, Miller J, Pirsch J. A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved graft survival at five-years. Transplantation 2002; 73(5): 775-82.

  34. Kaplan B, Schold JD, Meier-Kriesche HU. Long-term graft survival with Neoral and tacrolimus: a paired kidney analysis. J Am Soc Nephrol 2003; 14: 2980-4.

  35. Mayer AD. Chronic rejection and graft half-life: five-year follow-up of the European tacrolimus multicenter renal study. Transplant Proc 2002; 34(5): 1491-2.

  36. Helderman JH, Bennett WM, Cibrik DM, et al. Immunosuppression: practice and trends. Am J Transplant 2003; 3(suppl. 4): 41-52.

  37. Jin YJ, Burakoff SJ, Bierer BE. Molecular cloning of a 25-kDa high affinity rapamycin binding protein, FKBP25. J Biol Chem 1992; 267: 10942-5.

  38. Dumont FJ, Staruch MJ, Koprak SL, Melino MR Sigal NH. Distinct mechanisms of suppression of murine T cell activation by the related macrolides FK-506 and rapamycin. J Immunol 1990; 144:251-8.

  39. Heitman J, Movva NR, Hall MN. Target for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 1991; 253: 905-9.

  40. Sehgal SN. Rapamune (sirolimus, rapamycin): an overview and mechanism of action. Ther Drug Monit 1995; 17: 660

  41. Burke SE, Lubbers NL, Chen YW, et al. Meointimal formation after balloon-induced vascular injury in Yucatan mini-pigs is reduced by oral rapamycin. J Cardiovasc Pharmacol 1999; 33(6): 829

  42. Ikonen TS, Gummert JF, Hayase M, et al. sirolimus (rapamycin) halts and reverses progression of allograft vascular disease in non-human primates. Transplantation 2000; 70: 969.

  43. McTaggart RA, Gottlieb D, Brooks J, et al. sirolimus prolongs recovery from delayed graft function after cadaveric renal transplantation. Am J Transplant 2003; 3(4): 416-23.

  44. Giessing M, Budde K. sirolimus and lymphocele formation after kidney transplantation: an immunosuppressive medication as co-factor for a surgical problem? Nephrol Dial Transplant 2003; 18(2): 448-9.

  45. Kahan BD. Two-year results of multicenter phase III, randomized, controlled, safety and efficacy study of sirolimus to cyclosporine-based immunosuppressive regimens in renal transplantation. Transplant Proc 2003; 35(3 suppl): S37-51.

  46. Groth CG, Backman L, Morales JM, 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 1999; 67(7): 1036-42.

  47. Kreis H, Cisterne JM, Land W, et al. sirolimus in association with Mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation 2000; 69(7): 1252-60.

  48. Johnson RW, Kreis H, Oberbauer R y cols. sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 2001; 72(5): 777-86.

  49. Oberbauer R, Kresi H, Johnson RW, et al. Long-term improvement in renal function with sirolimus after early cyclosporine withdrawal in renal transplant recipients: 2-year results of the Rapamune maintenance regimen study. Transplantation 2003; 76(2): 364-70.

  50. Gonwa TA, Hricik DE, Brinker K, Grinyo JM, Schena FP. Improved renal function in sirolimus-treated renal transplant patients after early cyclosporine elimination. Transplantation 2002; 74(11): 1560-7.

  51. Mota A, Arias M, Taskinen, et al. sirolimus-based therapy following early cyclosporine withdrawal provides significantly improved renal histology and function at 3-years. Am J Transplant 2004; 4: 953-61.

  52. Sievers T, Rossi S, Ghobrial R, et al. Mycophenolate mofetil. Pharmacotherapy 1997; 17: 1178-97.

  53. Halloran P, Mathew T, Tomlanovich S, et al. Mycophenolate mofetil in renal allograft recipients: a pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection: the international Mycophenolate mofetil renal transplant study groups. Transplantation 1997; 63(1): 39-47.

  54. Meier-Kriesche HU, Steffen BJ, Hochberg AM, et al. Long-term use of Mycophenolate mofetil is associated with a reduction in the incidence and risk of late rejection. Am J Transplant 2003; 3: 68-73.

  55. Ojo AJ, Meier-Kriesche HU, Hanson JA, et al. Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection. Transplantation 2000; 69: 2405-9.

  56. Azuma H, Binder J, Heeman U, et al. Effects of RS61443 on functional and morphological changes in chronically rejecting rat kidney allografts. Transplantation 1995; 59: 460-6.

  57. Squifflet JP, Backman L, Claesson K y cols. Dose optimization of Mycophenolate mofetil when administered with a low dose of tacrolimus in cadaveric renal transplant recipients. Transplantation 2001; 72(1): 63-9.

  58. Weir MR, Fink JC, Hanes DS, et al. Chronic allograft nephropathy: Effect of cyclosporine reduction and addition of Mycophenolate mofetil on progression of renal disease. Transplant Proc 1999; 31: 1286-7.

  59. Weir MR, Traver Ward M, Blahut SA, et al. Long-term impact of discontinued or reduced calcineurin inhibitor in patients with chronic allograft nephropathy. Kidney Int 2001; 59: 1567-73.

  60. Granger DK. Enteric-coated Mycophenolate sodium: results of two pivotal global multicenter trials. Transplant Proc 2001; 33(7-8): 3241-4.

  61. Vincenti F, Pace D, Birnbaum J Lantz M. Pharmacokinetic and pharmacodynamic studies of one or two doses of daclizumab in renal transplantation. Am J Transplant 2003; 3(1): 50-2.

  62. Ekberg H, Backman L, Tufveson G, et al. daclizumab prevents acute rejection and improves patient survival post transplantation: 1-year pooled analysis. Transpl Int 2000; 13(2): 151-9.

  63. Morales-Buenrostro LE, Ortiz-Arroyo VM, Pérez-Garrido J, Correa-Rotter R, Alberú-Gómez J. Reducción en la frecuencia de rechazo agudo en receptores de trasplante renal de donador vivo con el uso de dosis reducida de daclizumab (2mg/kg). Revista de Resúmenes de la LIII Reunión Anual del Instituto Mexicano de Investigaciones Nefrológicas: 160.

  64. Bumgardner GL, Hardie I, Johnson RW, et al. Results of 3-year phase III clinical trials with daclizumab prophylaxis for prevention of acute rejection after renal transplantation. Transplantation 2001; 72(5): 839-45.

  65. Nashan B, Moore R, Amlot P, et al. Randomized trial of basiliximab vs. placebo for control of acute cellular rejection in renal allograft recipients: CHIB 201 international study group. Lancet 1997; 350(9086): 1193-8.

  66. Lawsen JG, Davies EA, Mourad G, et al. Randomized double-blind study of immunoprophylaxis with basiliximab, a chimerical anti-interleukin-2 receptor monoclonal antibody, in combination with Mycophenolate mofetil-containing triple therapy in renal transplantation. Transplantation 2003; 75(1): 37-43.

  67. Brennan DC, Flavin K, Lowell JA, et al. A randomized, double-blinded comparison of Thymoglobulin vs. Atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation 1999; 67(7): 1011-8.

  68. 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; 66(1): 29-37.

  69. Hardinger KL, Schnitzler M, Miller B y cols. Long-term comparison of Thymoglobulin versus Atgam for induction in adult renal transplantation: evidence of improved allograft survival at 5-years [abstr]. Am J Transplant 2003; 3: 556.

  70. Ortho Multicenter Transplant Study Group. A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. N Engl J Med 1985; 313: 337-42.

  71. Norman DJ, Kahana I, Stuart FP Jr, et al. A randomized clinical trial of induction therapy with OKT3 in kidney transplantation. Transplantation 1993; 55 :44-50.

  72. Knudsen PJ, Dinarello CA, Strom TB: Glucocorticoids inhibit transcription and post-transcriptional expression of interleukin-I. J Immunol 1987; 139: 4129-34.

  73. Zanker B, Waltz G, Wieder KJ, Strom TB. Evidence that glucocorticosteroids block expression of the human interleukin-6 gene by accessory cells. Transplantation 1990; 49: 183-5.

  74. Arya SK, Wong-Staal F, Gallo RC. Dexamethasone mediated inhibition of T cell growth factor and gamma interferon messenger RNA. J Immunol 1984; 133: 273-6.

  75. Almawi WY, Lipman ML, Stevens AC, Zanker B, Hadro ET, Strom TB. Abrogation of glucocorticosteroid-mediated inhibition of T-cell proliferation by the synergistic action of IL-1, IL-6, and IFN. J Immunol 1991; 146: 3523-7.

  76. Sinclair NR. Low-dose steroid therapy in cyclosporine-treated renal transplant recipients with well-functioning grafts. The Canadian multicentre transplant study group. Can Med Assoc J 1992; 147(5): 645-57.

  77. Wheeler DC, Steiger J. Evolution and etiology of cardiovascular diseases in renal transplant recipients. Transplantation 2000; 70: Suppl: SS41-SS45.

  78. Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant 2004; 4: 905-13.

  79. Kahan BD. Individuality: the barrier to optimal Immunosuppression. Nature Rev Immunol 2003; 3: 831-8.

  80. Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med 2004; 351: 2715-29.

  81. Matthews JF, Ramos E, Bluestone JA. Clinical trials of transplant tolerance: slow but steady progress. Am J Transplant 2003; 3: 794-803.




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