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Hypertonie und renale thrombotische Mikroangiopathie unter anti-angiogener Tumortherapie

Neue nephrologische Entitäten

Hypertension and renal thrombotic microangiopathy under anti-angiogenic tumor therapy

New nephrological entities

  • Leitthema
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Der Nephrologe Aims and scope

Zusammenfassung

Anti-angiogene Therapiekonzepte (AAT) mit gezielter Störung der VEGF (vascular endothelial growth factor)-Signalgebung (VSP) finden derzeit in der palliativ-onkologischen Behandlung von Tumorpatienten eine breite und stetig zunehmende Anwendung. Während diese nicht kurativen Therapien bestimmte Behandlungsendpunkte von mehreren Krebserkrankungen unter Umständen verbessern können, zeigen die klinischen Daten auch, dass sie für eine Reihe relevanter kardiovaskulärer und renaler Nebenwirkungen mit hohen Inzidenzraten verantwortlich sind. Nach aktuellen Schätzungen liegt beispielsweise die Rate für arterielle Hypertonie bei 19–24 % und könnte mit Anwendung potenterer VSP-Inhibitoren der zweiten Generation sogar noch deutlich höher sein. Das Auftreten von Proteinurie wurde in bis zu 20 % der behandelten Fälle beobachtet. Eine relativ häufig beschriebene Komplikation unter AAT ist zudem die Entwicklung einer renalen thrombotischen Mikroangiopathie (TMA), welche große Ähnlichkeiten mit der Präeklampsie hat, einer Erkrankung, die ebenfalls durch gestörte VSP und endotheliale Dysfunktion charakterisiert ist. Da die Nutzung dieser Medikamente weiter wächst sowie neue Variationen entwickelt werden, ergibt sich eine zunehmende Notwendigkeit für Nephrologen zu lernen, wie Toxizitäten von VSP-Inhibitoren richtig zu diagnostizieren und adäquat zu behandeln sind. Zugleich bietet sich aber auch die Gelegenheit zu versuchen, diese unerwünschten Nebeneffekte und klinischen Phänotypen auf die zugrunde liegenden molekularen Mechanismen zurückzuführen, die sie auslösen. Gemäß dem Konzept von personalisierter Medizin könnte dieses neue Wissen eines Tages genutzt werden, um anti-angiogene Therapieregime von Patienten zu individualisieren und dadurch zu verbessern.

Abstract

Anti-angiogenic therapies (AAT) targeting the VEGF signaling pathway (VSP) are increasingly used by oncologists for palliative treatment of patients with various solid tumors. While these non-curative drugs may improve certain treatment endpoints in selected cancer entities, clinical data suggest that they also cause a number of serious cardiovascular and renal side effects at rather high rates. For instance, the incidence of clinical hypertension has been estimated to be 19-24% and may be even higher with more potent second-generation VSP inhibitors. Onset of proteinuria has been observed in up to 20% of treated cases. Another frequently occurring renal complication under AAT is the development of renal thrombotic microangiopathy (TMA). This pattern of injury is the same as found in patients with pre-eclampsia, also a disease of disordered VEGF signaling and endothelial dysfunction. Because use of these medications continues to grow and many new formulations in development, there is an increasing need for the nephrologist to learn how to diagnose and manage VSP inhibitor toxicities. But at the same time there is a great opportunity to try connect these adverse events and clinical phenotypes back to the molecular mechanisms precipitating them. Consistent with the concept of personalized medicine, we may at some point use this new knowledge to individualize and hence optimize therapies for patients undergoing anti-angiogenic treatment.

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Authors and Affiliations

  1. Klinik für Innere Medizin und Nephrologie, Universitätsklinikum Gießen und Marburg, Philipps-Universität Marburg, Baldingerstraße 1, 35033, Marburg, Deutschland

    I. Grgic

  2. Klinik für Hämatologie, Onkologie und Immunologie, Universitätsklinikum Gießen und Marburg, Philipps-Universität Marburg, 35033, Marburg, Deutschland

    A. Burchert

  3. Renal Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

    B. D. Humphreys MD, PhD

  4. Dana Farber Cancer Institute, Lance Armstrong Foundation, Boston, Massachusetts, USA

    B. D. Humphreys MD, PhD

  5. Department of Medicine, Washington University Medical Center, St Louis, Missouri, USA

    B. D. Humphreys MD, PhD

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  1. I. Grgic
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  3. B. D. Humphreys MD, PhD
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I. Grgic, A. Burchert und B. D. Humphreys geben an, dass kein Interessenkonflikt besteht.

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M. Zeier, Heidelberg

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Grgic, I., Burchert, A. & Humphreys, B.D. Hypertonie und renale thrombotische Mikroangiopathie unter anti-angiogener Tumortherapie. Nephrologe 11, 20–27 (2016). https://doi.org/10.1007/s11560-015-0038-x

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