VEGF inhibition and renal thrombotic microangiopathy

Vera Eremina, J. Ashley Jefferson, Jolanta Kowalewska, Howard Hochster, Mark Haas, Joseph Weisstuch, Catherine Richardson, Jeffrey B. Kopp, M. Golam Kabir, Peter H. Backx, Hans Peter Gerber, Napoleone Ferrara, Laura Barisoni, Charles E. Alpers, Susan E. Quaggin

Research output: Contribution to journalArticle

965 Scopus citations

Abstract

The glomerular microvasculature is particularly susceptible to injury in thrombotic microangiopathy, but the mechanisms by which this occurs are unclear. We report the cases of six patients who were treated with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), in whom glomerular disease characteristic of thrombotic microangiopathy developed. To show that local reduction of VEGF within the kidney is sufficient to trigger the pathogenesis of thrombotic microangiopathy, we used conditional gene targeting to delete VEGF from renal podocytes in adult mice; this resulted in a profound thrombotic glomerular injury. These observations provide evidence that glomerular injury in patients who are treated with bevacizumab is probably due to direct targeting of VEGF by antiangiogenic therapy.

Original languageEnglish (US)
Pages (from-to)1129-1136
Number of pages8
JournalNew England Journal of Medicine
Volume358
Issue number11
DOIs
StatePublished - Mar 13 2008
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Eremina, V., Jefferson, J. A., Kowalewska, J., Hochster, H., Haas, M., Weisstuch, J., Richardson, C., Kopp, J. B., Kabir, M. G., Backx, P. H., Gerber, H. P., Ferrara, N., Barisoni, L., Alpers, C. E., & Quaggin, S. E. (2008). VEGF inhibition and renal thrombotic microangiopathy. New England Journal of Medicine, 358(11), 1129-1136. https://doi.org/10.1056/NEJMoa0707330