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Previous Volume 358:1129-1136 March 13, 2008 Number 11 Next

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SUMMARY

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.

Source Information

From the Samuel Lunenfeld Research Institute, Mount Sinai Hospital (V.E., S.E.Q.), and the Division of Nephrology, St. Michael's Hospital (S.E.Q.), University of Toronto, Toronto; the Division of Nephrology (J.A.J.) and the Department of Pathology (J.K., C.E.A.), University of Washington, Seattle; New York University Cancer Institute, New York (H.H.); the Johns Hopkins Medical Institutions, Baltimore (M.H.); the New York University School of Medicine, New York (J.W., L.B.); Pacific Nephrology Associates, Tacoma, WA (C.R.); Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (J.B.K.); the Heart and Stroke/Richard Lewar Centre of Excellence and the Toronto General Hospital Research Institute, Toronto (M.G.K., P.H.B.); Seattle Genetics, Bothell, WA (H.-P.G.); and Genentech, South San Francisco, CA (N.F.).

Drs. Eremina and Jefferson contributed equally to this article.

Address reprint requests to Dr. Quaggin at the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada, or at quaggin{at}mshri.on.ca.

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