Zusammenfassung
Hintergrund
Die Einführung einer effektiven und für die Patienten verträglichen Immunsuppression ermöglichte es, die Nierentransplantation als das Nierenersatzverfahren mit den besten Langzeitergebnissen zu etablieren. Dies hängt vor allem mit der Einführung einer Immunsuppression, bestehend aus den 3 Komponenten Calcineurininhibitoren (CNI), Proliferationsinhibitoren und Steroiden, zusammen. In den letzten Jahren ist die Verbesserung des Transplantatlangzeitüberlebens in den Fokus gerückt. Dabei stehen vor allem das chronische Transplantatversagen und der Verlust eines Nierentransplantats durch Tod des Empfängers im Fokus.
Ziel der Arbeit
Diese Zusammenfassung stellt die Erkenntnisse in Bezug auf die aktuellen immunsuppressiven Behandlungsprotokolle nach Nierentransplantation dar und gibt einen Ausblick auf zukünftige Behandlungsstrategien.
Ergebnisse
CNI, Proliferationsinhibitoren und Steroide stellen die Basis der heutigen Immunsuppression nach Nierentransplantation dar. Strategien zur Vermeidung bzw. Verminderung von CNI bzw. Steroiden mittels mTOR-Inhibitoren oder Biologika sind teilweise erfolgreich, wobei ungelöste Fragen vor allem in Bezug auf unerwünschte Wirkungen, Patientenkollektiv und Kosten bestehen. Infektionen, Tumoren und eine unzureichende Adhärenz, möglicherweise mit der Folge vermehrter antikörpervermittelter Abstoßungen, beeinträchtigen die langfristige Prognose nach Nierentransplantation.
Fazit
Zur Verbesserung der Langzeitprognose müssen Strategien zur Verminderung des kardiovaskulären Risikos und vor allem von chronischen antikörpervermittelten Abstoßungen weiterentwickelt werden. Dazu könnten neben neuen Immunsuppressiva auch Verbesserungen in der Diagnostik oder zellbasierte immunmodulierende Therapien geeignet sein.
Abstract
Background
The introduction of an effective and tolerable immunosuppression treatment for the patient enabled the establishment of kidney transplantation as the renal replacement therapy with the best long-term results. This is related to an immunosuppressive regimen consisting of calcineurin inhibitors (CNIs), antiproliferative compounds as well as steroids. The improvement of long-term graft survival has gained particular interest in recent years especially through new immunosuppressive protocols with mTOR inhibitors and biologics. However, although this would allow a reduction of CNIs and steroids with their unwanted effects, problems still exist with this approach. Of particular interest is chronic transplant failure and the loss of a transplant due to death of the recipient.
Objectives
This review focuses on the current immunosuppressive treatment protocols after kidney transplantation, the problems related to immunosuppression and provides an outlook on future therapeutic strategies.
Results
The combination of CNIs, proliferation inhibitors and steroids is currently the most common form of immunosuppressive therapy after kidney transplantation. The mTOR inhibitors can be used to reduce the dose of CNIs or steroids; however, more studies are needed to identify the patient group that would benefit most from this approach as well as the right strategy to switch to or to start de novo with an mTOR inhibitor. Whether biologics will become part of routine immunosuppression will be seen in the future. Infections, tumors and lack of adherence, probably associated with antibody-mediated rejection, all impair the long-term prognosis after kidney transplantation.
Conclusions
Strategies to minimize the cardiovascular risk and chronic antibody mediated rejections should be further developed in order to improve the long-term prognosis after kidney transplantation. New immunosuppressants together with new diagnostic tools and cell-based immunomodulatory therapies could help to achieve this goal.
Literatur
Gaston RS, Cecka JM, Kasiske BL et al (2010) Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure. Transplantation 90:68–74
Webster AC, Woodroffe RC, Taylor RS et al (2005) Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data. BMJ 331:810
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
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 9:1876–1885
Gelder T van, Gabardi S (2013) Methods, strengths, weaknesses, and limitations of bioequivalence tests with special regard to immunosuppressive drugs. Transpl Int 26:771–777
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 72:777–786
Lebranchu Y, Thierry A, Thervet E et al (2011) Efficacy and safety of early cyclosporine conversion to sirolimus with continued MMF: four-year results of the Postconcept study. Am J Transplant 11:1665–1675
Budde K, Becker T, Arns W et al (2011) Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial. Lancet 377:837–847
Liefeldt L, Brakemeier S, Glander P et al (2012) Donor-specific HLA antibodies in a cohort comparing everolimus with cyclosporine after kidney transplantation. Am J Transplant 12:1192–1198
Perbos E, Juinier E, Guidicelli G et al (2014) Evolution of donor-specific antibodies (DSA) and incidence of de novo DSA in solid organ transplant recipients after switch to everolimus alone or associated with low dose of calcineurin inhibitors. Clin Transplant 28:1054–1060
Croze LE, Tetaz R, Roustit M et al (2014) Conversion to mammalian target of rapamycin inhibitors increases risk of de novo donor-specific antibodies. Transpl Int 27:775–783
Charpentier B, Medina Pestana JO, Del C Rial M et al (2013) Long-term exposure to belatacept in recipients of extended criteria donor kidneys. Am J Transplant 13:2884–2891
Rostaing L, Vincenti F, Grinyo J et al (2013) Long-term belatacept exposure maintains efficacy and safety at 5 years: results from the long-term extension of the BENEFIT study. Am J Transplant 13:2875–2883
Ferguson R, Grinyo J, Vincenti F et al (2011) Immunosuppression with belatacept-based, corticosteroid-avoiding regimens in de novo kidney transplant recipients. Am J Transplant 11:66–76
Kim EJ, Kwun J, Gibby AC et al (2014) Costimulation blockade alters germinal center responses and prevents antibody-mediated rejection. Am J Transplant 14:59–69
Vincenti F, Charpentier B, Vanrenterghem Y et al (2010) A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant 10:535–546
Ciancio G, Burke GW, Gaynor JJ et al (2005) A randomized trial of three renal transplant induction antibodies: early comparison of tacrolimus, mycophenolate mofetil, and steroid dosing, and newer immune-monitoring. Transplantation 80:457–465
Ciancio G, Gaynor JJ, Guerra G et al (2014) Randomized trial of three induction antibodies in kidney transplantation: long-term results. Transplantation 97:1128–1138
Webster AC, Ruster LP, McGee R et al (2010) Interleukin 2 receptor antagonists for kidney transplant recipients. Cochrane Database Syst Rev (1):CD003897
Sellares J, Freitas DG de, Mengel M et al (2012) Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant 12:388–399
Lefaucheur C, Nochy D, Andrade J et al (2009) Comparison of combination Plasmapheresis/IVIg/anti-CD20 versus high-dose IVIg in the treatment of antibody-mediated rejection. Am J Transplant 9:1099–1107
Waiser J, Budde K, Schutz M et al (2012) Comparison between bortezomib and rituximab in the treatment of antibody-mediated renal allograft rejection. Nephrol Dial Transplant 27:1246–1251
Billing H, Rieger S, Ovens J et al (2008) Successful treatment of chronic antibody-mediated rejection with IVIG and rituximab in pediatric renal transplant recipients. Transplantation 86:1214–1221
Fehr T, Rusi B, Fischer A et al (2009) Rituximab and intravenous immunoglobulin treatment of chronic antibody-mediated kidney allograft rejection. Transplantation 87:1837–1841
Fehr T, Stussi G (2012) ABO-incompatible kidney transplantation. Curr Opin Organ Transplant 17:376–385
Prendergast MB, Gaston RS (2010) Optimizing medication adherence: an ongoing opportunity to improve outcomes after kidney transplantation. Clin J Am Soc Nephrol 5:1305–1311
Stallone G, Schena A, Infante B et al (2005) Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med 352:1317–1323
Alberu J, Pascoe MD, Campistol JM et al (2011) Lower malignancy rates in renal allograft recipients converted to sirolimus-based, calcineurin inhibitor-free immunotherapy: 24-month results from the CONVERT trial. Transplantation 92:303–310
Wohlfahrtova M, Viklicky O (2014) Recent trials in immunosuppression and their consequences for current therapy. Curr Opin Organ Transplant 19:387–394
Einhaltung ethischer Richtlinien
Interessenkonflikt. B. Schamberger, D. Sollinger und J. Lutz geben an, dass kein Interessenkonflikt besteht.
Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schamberger, B., Sollinger, D. & Lutz, J. Immunsuppressive Therapie nach Nierentransplantation. Nephrologe 10, 9–15 (2015). https://doi.org/10.1007/s11560-014-0904-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11560-014-0904-y
Schlüsselwörter
- Nierenersatzverfahren
- Transplantatüberleben
- Chronisches Transplantatversagen
- Antikörpervermittelte Abstoßung
- Adhärenz