VEGF inhibition and renal thrombotic microangiopathy.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Eremina, V; Jefferson, JA; Kowalewska, J; Hochster, H; Haas, M; Weisstuch, J; Richardson, C; Kopp, JB; Kabir, MG; Backx, PH; Gerber, H-P; Ferrara, N; Barisoni, L; Alpers, CE; Quaggin, SE

Published Date

  • March 2008

Published In

Volume / Issue

  • 358 / 11

Start / End Page

  • 1129 - 1136

PubMed ID

  • 18337603

Pubmed Central ID

  • 18337603

Electronic International Standard Serial Number (EISSN)

  • 1533-4406

International Standard Serial Number (ISSN)

  • 0028-4793

Digital Object Identifier (DOI)

  • 10.1056/NEJMoa0707330

Language

  • eng