[HTML][HTML] VEGF inhibition and renal thrombotic microangiopathy

V Eremina, JA Jefferson, J Kowalewska… - … England Journal of …, 2008 - Mass Medical Soc
V Eremina, JA Jefferson, J Kowalewska, H Hochster, M Haas, J Weisstuch, C Richardson…
New England Journal of Medicine, 2008Mass Medical Soc
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 …
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.
The New England Journal Of Medicine