Zusammenfassung
Die Nierentransplantation ist die bestmögliche Therapie der terminalen Niereninsuffizienz hinsichtlich Lebensqualität, Rehabilitationsgrad und Patientenüberleben. Durch Verhinderung von akuter Transplantatabstoßung und chronischer Transplantatdysfunktion soll eine optimale immunsuppressive Therapie die Funktion der transplantierten Organe langfristig sichern und dazu beitragen, den vorzeitigen Tod des Empfängers zu vermeiden.
In den letzten 10 Jahren kam es mit der Einführung neuer Immunsuppressiva zu einer deutlichen Reduktion akuter Abstoßungskrisen von ca. 50% auf ca. 15–30%. Aber unverändert geht die Suche nach neuen Substanzklassen weiter, die nicht nur zur effektiven Prophylaxe akuter Rejektionen beitragen, sondern auch die chronische Transplantatdysfunktion günstig beeinflussen und zumindest nicht zur weiteren Aggravation dieses multifaktoriellen Prozesses beitragen.
Ausgehend von einer kurzen Darstellung des 3-Signal-Modells der Immunaktivierung werden wesentliche Angriffspunkte und Eigenschaften der zur Verfügung stehenden Immunsuppressiva erläutert. Da sich die Aufgaben der Immunsuppression in den verschiedenen Phasen nach der Transplantation unterscheiden, ist eine phasengerechte Adaptation erforderlich. Derzeit wird in Deutschland bei den meisten Transplantationen initial eine Kombinationstherapie bestehend aus einem Calcineurin-Inhibitor (CNI, Cyclosporin oder Tacrolimus), einem Glukokortikoid (Prednisolon oder Methylprednisolon) und der Mycophenolsäure (MPA) eingesetzt und unter Umständen mit einem Antikörper (z. B. IL-2R-Antikörper) zur Induktion kombiniert. Im Gegensatz zu der eher übersichtlichen Situation vor ca. 10 Jahren ist heute ein ausgeprägtes Spezialwissen bezüglich genauem Wirkungsmechanismus, Nebenwirkungen und Interaktionspotential unerlässlich, um eine patientenadaptierte bestmögliche Immunsuppression durchzuführen.
Zunehmend werden vermehrt individuelle immunsuppressive Behandlungsstrategien eingesetzt, die sich an den Eigenschaften des Medikaments und an seinen Nebenwirkungen ebenso orientieren wie an den Besonderheiten des Empfängers, des Spenders und des transplantierten Organs (wie z. B. Immunologie, Ischämiezeit). Dazu gehört die frühestmögliche Reduktion oder Elimination von einzelnen Immunsuppressiva ebenso wie der Einsatz neuer diagnostischer und genetischer Marker, mit denen das individuelle Wechselspiel zwischen Empfänger und Transplantat besser charakterisiert werden kann und die neben einer verbesserten supportiven Therapie das Langzeitüberleben weiter verbessert.
Abstract
Renal transplantation is by far the best therapeutic option for end-stage kidney disease with respect to quality of life, psychosocial rehabilitation, and even patient survival. Optimal immunosuppressive therapy should provide effective prophylaxis of both acute rejection and chronic allograft dysfunction. Thus immunosuppressive therapy should help to maintain good renal function and could help to prevent premature death of the recipient. With the introduction of new immunosuppressants over the last decade a dramatic reduction of acute rejection rates from approximately 50% to 15–30% could be achieved.
However, the search for novel immunosuppressive drugs continues, drugs which not only lead to effective prevention of acute rejection, but also have an impact on chronic allograft dysfunction and prevent further deterioration of this multifactorial process. Based on a short presentation of the “three signal model” of immunoactivation, the most important mechanisms and characteristics of the presently available immunosuppressants are described. Because the immunosuppressive objectives change over time, a phase-dependent adaptation is necessary. At present, most centers in Germany use an immunosuppressive combination therapy, consisting of a calcineurin inhibitor (CNI; cyclosporine or tacrolimus), a glucocorticoid (prednisolone or methylprednisolone), and mycophenolic acid (MPA), which is eventually combined with an antibody (e.g., IL-2R antibody) for induction. In contrast to the clear situation 10 years ago, highly specialized knowledge is required today with respect to mechanism of action, side effects, and potential interactions. This may enable the physician to adopt patient-oriented optimal immunosuppression. In the near future more individualized treatment options will be employed, which are adapted to the characteristics and side effects of the immunosuppressant, as well as to the characteristics of the donor, the recipient, and the transplanted organ such as immunology and ischemia.
Another aspect is the reduction or elimination of some immunosuppressants at the earliest possible time. With new diagnostic and genetic markers the relationship between recipient and transplanted organ will be characterized better in the future and therapy will become more individualized. Altogether, these measures as well as optimized supportive therapy will help to further improve the longevity of the transplanted organ.
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Der korrespondierende Autor weist auf eine Verbindung mit folgender Firma/Firmen hin: Forschungsunterstützung von Roche AG, Wyeth, Astellas Pharma, Novatis Pharma.
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Budde, K., Giessing, M., Liefeldt, L. et al. Moderne Immunsuppressiva nach Nierentransplantation. Urologe 45, 9–17 (2006). https://doi.org/10.1007/s00120-005-0958-6
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DOI: https://doi.org/10.1007/s00120-005-0958-6