Zusammenfassung
Durch die Immunsuppression mit Calcineurininhibitoren (CNI) zusammen mit Glukokortikoiden konnte das Auftreten akuter Abstoßungen nach Nierentransplantation deutlich reduziert werden. Allerdings trägt die Nephrotoxizität der CNI zum chronischen Transplantatversagen bei und die Nebenwirkungen der Glukokortikoide zu einer Verschlechterung des kardiovaskulären Risikoprofils. Beim Absetzen von CNI oder Glukokortikoiden und Fortführen mit DNA-Synthesehemmern bzw. bei der Konversion muss individuell im Hinblick auf das Risiko einer akuten Abstoßung, die Transplantatfunktion und das Nebenwirkungsprofil der Präparate entschieden werden. In Kombination mit Mycophenolatmofetil können CNI sicher reduziert werden, allerdings können diese CNI nicht ersetzen. Eine Konversion von CNI auf mTOR-Inhibitoren ist möglich bei Patienten mit einer GFR >40 ml/min, einem Urin-Protein/Kreatinin-Quotienten ≤0,11 und unter engmaschiger Kontrolle der Transplantatfunktion sowie des Patienten im Hinblick auf mögliche Nebenwirkungen. Eine Vermeidung von CNI- oder Glukokortikoid-basierten Regimen mit Hilfe neuerer Immunsuppressiva ist möglich, allerdings fehlen noch ausreichende Daten für den Langzeitverlauf.
Abstract
The introduction of calcineurin inhibitors (CNIs) and their combination with steroids has led to a decreased incidence of acute rejection episodes in patients after kidney transplantation. However, the nephrotoxicity of CNIs contributes to chronic allograft injury, and the side effects of steroids contribute to a deterioration of the cardiovascular risk profile. The decision to withdraw CNIs or steroids and continue with, or change to, DNA synthesis inhibitors needs to be made individually on the basis of the risk of acute rejection, the function of the graft, and side effects of the applied drugs. Conversion from CNIs to mTOR inhibitors is feasible in patients with a baseline glomerular filtration rate >40 ml/min and a urine protein/creatinine ratio ≤0.11 and with close monitoring of side effects. CNIs or steroid-free immunosuppression may be successful with new immunosuppressants, yet more data are required with respect to long-term results.
Literatur
Eigler FW (2002) Zur Geschichte der Nierentransplantation in Deutschland. Zentralbl Chir 127:1001–1008
Meier-Kriesche HU, Schold JD, Kaplan B (2004) Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies? Am J Transplant 4:1289–1295
European Renal Association und European Society for Organ Transplantation (2000) European best practice guidelines for renal transplantation (part 1). Nephrol Dial Transplant 15(Suppl 7):1–85
Meier-Kriesche HU, Li S, Gruessner RW, Fung JJ et al (2006) Immunosuppression: evolution in practice and trends, 1994–2004. Am J Transplant 6:1111–1131
Kapturczak MH, Meier-Kriesche HU, Kaplan B (2004) Pharmacology of calcineurin antagonists. Transplant Proc 36:25S–32S
Merville P (2005) Combating chronic renal allograft dysfunction: optimal immunosuppressive regimens. Drugs 65:615–631
Olyaei AJ, de Mattos AM, Bennett WM (2001) Nephrotoxicity of immunosuppressive drugs: new insight and preventive strategies. Curr Opin Crit Care 7:384–389
Nankivell BJ, Borrows RJ, Fung CL et al (2003) The natural history of chronic allograft nephropathy. N Engl J Med 349:2326–2333
Flechner SM, Kobashigawa J, Klintmalm G (2008) Calcineurin inhibitor-sparing regimens in solid organ transplantation: focus on improving renal function and nephrotoxicity. Clin Transplant 22:1–15
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 7:560–570
Opelz G, Dohler B (2008) Influence of time of rejection on long-term graft survival in renal transplantation. Transplantation 85:661–666
Danger R, Giral M, Soulillou JP, Brouard S (2008) Rationale and criteria of eligibility for calcineurin inhibitor interruption following kidney transplantation. Current Opin Organ Transplantation 13:609–613
Weir MR, Ward MT, Blahut SA et al (2001) Long-term impact of discontinued or reduced calcineurin inhibitor in patients with chronic allograft nephropathy. Kidney Int 59:1567–1573
Giessing M, Fuller TF, Tuellmann M et al (2007) Steroid- and calcineurin inhibitor free immunosuppression in kidney transplantation: state of the art and future developments. World J Urol 25:325–332
Zanker B, Schneeberger H, Rothenpieler U et al (1998) Mycophenolate mofetil-based, cyclosporine-free induction and maintenance immunosuppression: first-3-months analysis of efficacy and safety in two cohorts of renal allograft recipients. Transplantation 66:44–49
Vincenti F, Ramos E, Brattstrom C et al (2001) Multicenter trial exploring calcineurin inhibitors avoidance in renal transplantation. Transplantation 71:1282–1287
Webster AC, Lee VW, Chapman JR, Craig JC (2006) Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients. Cochrane Database Syst Rev:CD004290
Allison AC, Eugui EM (2000) Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47:85–118
Sollinger HW (2004) Mycophenolates in transplantation. Clin Transplant 18:485–492
Halloran P, Mathew T, Tomlanovich S et al (1997) 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 63:39–47
Remuzzi G, Lesti M, Gotti E et al (2004) Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial. Lancet 364:503–512
Arns W, Cibrik DM, Walker RG et al (2006) Therapeutic drug monitoring of mycophenolic acid in solid organ transplant patients treated with mycophenolate mofetil: review of the literature. Transplantation 82:1004–1012
Andrassy J, Graeb C, Rentsch M et al (2005) mTOR inhibition and its effect on cancer in transplantation. Transplantation 80:S171–S174
Dean PG, Lund WJ, Larson TS et al (2004) Wound-healing complications after kidney transplantation: a prospective, randomized comparison of sirolimus and tacrolimus. Transplantation 77:1555–1561
Buhaescu I, Izzedine H, Covic A (2006) Sirolimus-challenging current perspectives. Ther Drug Monit 28:577–584
Dunn C, Croom KF (2006) Everolimus: a review of its use in renal and cardiac transplantation. Drugs 66:547–570
McTaggart RA, Gottlieb D, Brooks J et al (2003) Sirolimus prolongs recovery from delayed graft function after cadaveric renal transplantation. Am J Transplant 3:416–423
Ekberg H, Tedesco-Silva H, Demirbas A et al (2007) Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 357:2562–2575
Nashan B, Curtis J, Ponticelli C et al (2004) Everolimus and reduced-exposure cyclosporine in de novo renal-transplant recipients: a three-year phase II, randomized, multicenter, open-label study. Transplantation 78:1332–1340
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 18:22–28
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 87:233–242
Wali RK, Weir MR (2008) Chronic allograft dysfunction: can we use mammalian target of rapamycin inhibitors to replace calcineurin inhibitors to preserve graft function? Current Opin Organ Transplantation 13:614–621
Stahn C, Lowenberg M, Hommes DW, Buttgereit F (2007) Molecular mechanisms of glucocorticoid action and selective glucocorticoid receptor agonists. Mol Cell Endocrinol 275:71–78
Lowenberg M, Verhaar AP, Bilderbeek J et al (2006) Glucocorticoids cause rapid dissociation of a T-cell-receptor-associated protein complex containing LCK and FYN. EMBO Rep 7:1023–1029
Pascual J, Zamora J, Galeano C et al (2009) Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev:CD005632
Opelz G, Dohler B, Laux G (2005) Long-term prospective study of steroid withdrawal in kidney and heart transplant recipients. Am J Transplant 5:720–728
Interessenkonflikt
Der korrespondierende Autor weist auf folgende Beziehung/en hin: Forschungsunterstützung von Astellas, Roche, Novartis, Wyeth.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Becker, S., Witzke, O. Management der Immunsuppression nach Nierentransplantation. Nephrologe 4, 221–229 (2009). https://doi.org/10.1007/s11560-008-0274-4
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11560-008-0274-4