VEGF inhibition and renal thrombotic microangiopathy

被引：1149

作者：

Eremina, Vera ^{[1
,2
]}

Jefferson, J. Ashley ^{[4
,5
]}

Kowalewska, Jolanta

Hochster, Howard ^{[6
]}

Haas, Mark ^{[7
]}

Weisstuch, Joseph ^{[8
]}

Richardson, Catherine ^{[9
]}

Kopp, Jeffrey B. ^{[10
]}

Kabir, M. Golam ^{[11
,12
]}

Backx, Peter H. ^{[11
,12
]}

Gerber, Hans-Peter ^{[13
]}

Ferrara, Napoleone ^{[14
]}

Barisoni, Laura ^{[8
]}

Alpers, Charles E. ^{[5
]}

Quaggin, Susan E. ^{[1
,2
,3
]}

机构：

[1] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[2] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[3] Univ Toronto, St Michaels Hosp, Div Nephrol, Toronto, ON M5B 1W8, Canada

[4] Univ Washington, Div Nephrol, Seattle, WA 98195 USA

[5] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

[6] NYU, Inst Canc, New York, NY USA

[7] Johns Hopkins Med Inst, Baltimore, MD 21205 USA

[8] NYU, Sch Med, New York, NY USA

[9] Pacific Nephrol Assoc, Tacoma, WA USA

[10] NIDDKD, Kidney Dis Sect, Bethesda, MD 20892 USA

[11] Heart & Stroke Richard Lewar Ctr Excellence, Toronto, ON, Canada

[12] Toronto Gen Hosp, Res Inst, Toronto, ON, Canada

[13] Seattle Genet, Bothell, WA USA

[14] Genentech Inc, San Francisco, CA 94080 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2008年 / 358卷 / 11期

关键词：

D O I：

10.1056/NEJMoa0707330

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1129 / 1136

页数：8

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