VEGF inhibition and renal thrombotic microangiopathy |
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Authors: | Eremina Vera Jefferson J Ashley Kowalewska Jolanta Hochster Howard Haas Mark Weisstuch Joseph Richardson Catherine Kopp Jeffrey B Kabir M Golam Backx Peter H Gerber Hans-Peter Ferrara Napoleone Barisoni Laura Alpers Charles E Quaggin Susan E |
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Institution: | Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. |
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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. |
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