VEGF Inhibition and Renal Thrombotic Microangiopathy

作者：Vera Eremina, J. Ashley Jefferson, Jolanta Kowalewska, Howard S. Höchster, Mark Haas, Joseph Weisstuch, C. A. Richardson, Jeffrey B. Kopp, M. Golam Kabir, Peter H. Backx, Hans-Peter Gerber, N. Ferrara, Laura Barisoni, Charles E. Alpers, Susan E. Quaggin · 发表于：New England Journal of Medicine · 年份：2008 · DOI：10.1056/nejmoa0707330 · 被引用次数：1514 · 研究领域：Renal Diseases and Glomerulopathies、Renal and Vascular Pathologies、Complement system in diseases

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.