Umstellung von einem Calcineurin-Inhibitor auf eine Sirolimus-basierte Therapie nach Nierentransplantation

Zusammenfassung

Sirolimus ist der erste Vertreter aus der Substanzgruppe der „mammalian Target of Rapamycin – (mTOR)-Inhibitoren“. In zahlreichen Studien konnte eine Verbesserung oder Stabilisierung der Nierenfunktion nach Umstellung von einer Calcineurin-Inhibitor (CNI)-basierten Erhaltungs-Immunsuppression auf Sirolimus gezeigt werden. Die bereits bestehenden Evidenz-basierten Konsensus-Empfehlungen zur Konversion von einem CNI- auf eine Sirolimus-basierte Therapie nach Nierentransplantation aus dem Jahre 2004 werden hier aktualisiert, um neuen Studienergebnissen und Erfahrungen Rechnung zu tragen. Indikationen, für die eine Empfehlung zur Konversion ausgesprochen werden kann, umfassen progrediente Funktionsstörungen des Nierentransplantats, Malignome (vor allem das Kaposi-Sarkom und das Spinalzellkarzinom der Haut) sowie intolerable neurotoxische und kosmetische Nebenwirkungen der Calcineurin-Inhibitoren. Klinische Erfahrungen zeigen, dass die Konversion entsprechender Patienten schon in der Frühphase (z. B. ab dem dritten Monat) nach Transplantation sicher durchgeführt werden kann. Einschränkungen liegen bei einer vorbestehenden signifikanten Proteinurie vor, aber auch Wundheilungsstörungen nach chirurgischen Eingriffen können den Einsatz limitieren. Für eine geplante Umstellung bei Patienten mit geringem bzw. mittlerem immunologischen Risiko wird keine Aufsättigungs-Dosis empfohlen. In der Erhaltungstherapie empfiehlt es sich, die Dosierung von Sirolimus an den Bluttalspiegeln, mit einem Zielbereich von 5–8 ng/ml, zu orientieren. Nach einer Einstellung auf Sirolimus häufig zu beobachtende unerwünschte, dosisabhängige Nebenwirkungen sind Stomatitis, Ödeme und Hautveränderungen. Um einen vorzeitigen Therapieabbruch zu vermeiden, ist ein konsequentes Nebenwirkungsmanagement erforderlich.

Schlüsselwörter

Calcineurin-Inhibitor-Toxizität - mTOR-Inhibitor - Sirolimus - chronische Allograft- Nephropathie

Keywords

calcineurin inhibitor toxicity - mTOR inhibitor - sirolimus - chronic allograft nephropathy

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