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Immunsuppression nach Nierentransplantation

Aktuelle Datenlage zur Vermeidung und Reduktion der Calcineurininhibitoren

Immunosuppression after renal transplantation

Current data on avoidance and reduction of calcineurin inhibitors

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Der Nephrologe Aims and scope

Zusammenfassung

Trotz entscheidender Verbesserung des Transplantatüberlebens in der Frühphase nach Nierentransplantation, insbesondere durch Reduktion der Rate akuter Rejektionen innerhalb des ersten Jahres, bleibt der langfristige Erhalt der Transplantatfunktion eine Herausforderung. Die Calcineurininhibitortoxizität ist eine Ursache der chronischen Transplantatdysfunktion. Die Entwicklung neuer immunsuppressiver Substanzen und Konzepte, welche die Vermeidung oder Reduktion der Calcineurininhibitoren zum Ziel haben, scheint ein wesentliches Element für den Erhalt einer langfristigen Organfunktion zu sein. Vorgestellt werden deshalb insbesondere neue Immunsuppressiva und immunsuppressive Konzepte, welche die Vermeidung oder den Entzug von Calcineurininhibitoren zum Ziel haben.

Abstract

Short term allograft survival after kidney transplantation has substantially improved in recent years. This is mainly attributable to a lower rate of acute rejection episodes during the first year after transplantation. However, maintenance of long term kidney allograft function is still a challenge. Calcineurin inhibitors greatly reduce rejection episodes during the first year after transplantation, however, they also contribute to graft dysfunction in the long term due to calcineurin inhibitor toxicity. Therefore, there is a need for new immunosuppressive agents and new concepts or drug regimes which are equally effective as calcineurin inhibitors without the adverse effects on the kidney allograft. Therefore this overview will focus on new drug regimens that allow the reduction or withdrawal of calcineurin inhibitors.

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Literatur

  1. Wolfe RA, Ashby VB, Milford EL et al (1999) Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation and recipients of a first cadaveric transplant. N Engl J Med 341(23):1725–1730

    Article  CAS  PubMed  Google Scholar 

  2. Nankivell BJ, Borrows RJ, Fung CL et al (2003) The natural history of chronic allograft nephropathy. N Engl J Med 349(24):2326–2333

    Article  CAS  PubMed  Google Scholar 

  3. Salvadori M, Holzer H, Mattos A de et al (2004) Enteric-coated mycophenolate sodium is therapeutically equivalent to mycophenolate mofetil in de novo renal transplant patients. Am J Transplant 4(2):231–236

    Article  CAS  PubMed  Google Scholar 

  4. Kasiske BL, Chakkera HA, Louis TA, Ma JZ (2000) A meta-analysis of immunosuppression withdrawal trials in renal transplantation. J Am Soc Nephrol 11(10):1910–1917

    CAS  PubMed  Google Scholar 

  5. Moore J, Middleton L, Cockwell P et al (2009) Calcineurin inhibitor sparing with mycophenolate in kidney transplantation: a systematic review and meta-analysis. Transplantation 87(4):591–605

    Article  CAS  PubMed  Google Scholar 

  6. Ekberg H, Grinyo J, Nashan B et al (2007) Cyclosporine sparing with mycophenolate mofetil, daclizumab and corticosteroids in renal allograft recipients: the CAESAR Study. Am J Transplant 7(3):560–570

    Article  CAS  PubMed  Google Scholar 

  7. Ekberg H, Tedesco-Silva H, Demirbas A et al (2007) Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 357(25):2562–2575

    Article  CAS  PubMed  Google Scholar 

  8. Ekberg H, Bernasconi C, Tedesco-Silva H et al (2009) Calcineurin inhibitor minimization in the Symphony study: observational results 3 years after transplantation. Am J Transplant 9(8):1876–1885

    Article  CAS  PubMed  Google Scholar 

  9. Kahan BD (2000) 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

    Article  CAS  PubMed  Google Scholar 

  10. MacDonald AS (2001) A worldwide, phase III, randomized, controlled, safety and efficacy study of a sirolimus/cyclosporine regimen for prevention of acute rejection in recipients of primary mismatched renal allografts. Transplantation 71(2):271–280

    Article  CAS  PubMed  Google Scholar 

  11. Groth CG, Backman L, Morales JM et al (1999) 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

    Article  CAS  PubMed  Google Scholar 

  12. Morales JM, Wramner L, Kreis H et al (2002) Sirolimus does not exhibit nephrotoxicity compared to cyclosporine in renal transplant recipients. Am J Transplant 2(5):436–442

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Flechner SM, Goldfarb D, Solez K et al (2007) Kidney transplantation with sirolimus and mycophenolate mofetil-based immunosuppression: 5-year results of a randomized prospective trial compared to calcineurin inhibitor drugs. Transplantation 83(7):883–892

    Article  CAS  PubMed  Google Scholar 

  15. Johnson RW, Kreis H, Oberbauer R et al (2001) Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 72(5):777–786

    Article  CAS  PubMed  Google Scholar 

  16. Kreis H, Oberbauer R, Campistol JM et al (2004) Long-term benefits with sirolimus-based therapy after early cyclosporine withdrawal. J Am Soc Nephrol 15(3):809–817

    Article  CAS  PubMed  Google Scholar 

  17. Oberbauer R, Segoloni G, Campistol JM et al (2005) Early cyclosporine withdrawal from a sirolimus-based regimen results in better renal allograft survival and renal function at 48 months after transplantation. Transpl Int 18(1):22–28

    Article  CAS  PubMed  Google Scholar 

  18. Baboolal K (2003) A phase III prospective, randomized study to evaluate concentration-controlled sirolimus (rapamune) with cyclosporine dose minimization or elimination at six months in de novo renal allograft recipients. Transplantation 75(8):1404–1408

    Article  CAS  PubMed  Google Scholar 

  19. Gonwa TA, Hricik DE, Brinker K et al (2002) Improved renal function in sirolimus-treated renal transplant patients after early cyclosporine elimination. Transplantation 74(11):1560–1567

    Article  CAS  PubMed  Google Scholar 

  20. Mota A, Arias M, Taskinen EI et al (2004) Sirolimus-based therapy following early cyclosporine withdrawal provides significantly improved renal histology and function at 3 years. Am J Transplant 4(6):953–961

    Article  CAS  PubMed  Google Scholar 

  21. Ruiz JC, Campistol JM, Grinyo JM et al (2004) Early cyclosporine a withdrawal in kidney-transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesions. Transplantation 78(9):1312–1318

    Article  CAS  PubMed  Google Scholar 

  22. Anil Kumar MS, Heifets M, Fyfe B et al (2005) Comparison of steroid avoidance in tacrolimus/mycophenolate mofetil and tacrolimus/sirolimus combination in kidney transplantation monitored by surveillance biopsy. Transplantation 80(6):807–814

    Article  Google Scholar 

  23. Schena FP, Pascoe MD, Alberu J et al (2009) Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation 87(2):233–242

    Article  CAS  PubMed  Google Scholar 

  24. Lebranchu Y, Thierry A, Toupance O et al (2009) Efficacy on renal function of early conversion from cyclosporine to sirolimus 3 months after renal transplantation: concept study. Am J Transplant 9(5):1115–1123

    Article  CAS  PubMed  Google Scholar 

  25. Vitko S, Margreiter R, Weimar W et al (2004) Everolimus (certican) 12-month safety and efficacy versus mycophenolate mofetil in de novo renal transplant recipients. Transplantation 78(10):1532–1540

    Article  PubMed  Google Scholar 

  26. Lorber MI, Mulgaonkar S, Butt KM et al (2005) Everolimus versus mycophenolate mofetil in the prevention of rejection in de novo renal transplant recipients: a 3-year randomized, multicenter, phase III study. Transplantation 80(2):244–252

    Article  CAS  PubMed  Google Scholar 

  27. Lorber MI, Ponticelli C, Whelchel J et al (2005) Therapeutic drug monitoring for everolimus in kidney transplantation using 12-month exposure, efficacy and safety data. Clin Transplant 19(2):145–152

    Article  PubMed  Google Scholar 

  28. Vitko S, Margreiter R, Weimar W et al (2005) Three-year efficacy and safety results from a study of everolimus versus mycophenolate mofetil in de novo renal transplant patients. Am J Transplant 5(10):2521–2530

    Article  CAS  PubMed  Google Scholar 

  29. Nashan B (2004) Maximizing the clinical outcome with mTOR inhibitors in the renal transplant recipient: defining the role of calcineurin inhibitors. Transpl Int 17(6):279–285

    Article  CAS  PubMed  Google Scholar 

  30. Pascual J (2005) Concentration-controlled everolimus (Certican): combination with reduced dose calcineurin inhibitors. Transplantation 79(9 Suppl):S76–S79

    Article  CAS  PubMed  Google Scholar 

  31. Halloran PF (2004) Immunosuppressive drugs for kidney transplantation. N Engl J Med 351(26):2715–2729

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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  1. Nierenzentrum Heidelberg, Medizinische Universitätsklinik Heidelberg, Im Neuenheimer Feld 162, 69120, Heidelberg, Deutschland

    C. Morath, M. Zeier & C. Sommerer

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  1. C. Morath
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  2. M. Zeier
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  3. C. Sommerer
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Correspondence to C. Morath.

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Morath, C., Zeier, M. & Sommerer, C. Immunsuppression nach Nierentransplantation. Nephrologe 5, 108–117 (2010). https://doi.org/10.1007/s11560-009-0370-0

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