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

共 19 条

[11] Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia [J].

Li, Zhihe ;

Zhang, Ying ;

Ma, Jing Ying ;

Kapoun, Ann M. ;

Shao, Qiming ;

Kerr, Irene ;

Lam, Andrew ;

O'Young, Gilbert ;

Sannajust, Frederick ;

Stathis, Peter ;

Schreiner, George ;

Karumanchi, S. Ananth ;

Protter, Andrew A. ;

Pollitt, N. Stephen .

HYPERTENSION, 2007, 50 (04) :686-692

[12] Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfimction, hypertension, and proteinuria in preeclampsia [J].

Maynard, SE ;

Min, JY ;

Merchan, J ;

Lim, KH ;

Li, JY ;

Mondal, S ;

Libermann, TA ;

Morgan, LP ;

Sellke, FW ;

Stillman, IE ;

Epstein, FH ;

Sukhatme, VP ;

Karumanchi, SA .

JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (05) :649-658

[13] Effects of filtration rate on the glomerular barrier and clearance of four differently shaped molecules [J].

Ohlson, M ;

Sörenson, J ;

Lindström, K ;

Blom, AM ;

Fries, E ;

Haraldsson, B .

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2001, 281 (01) :F103-F113

[14] VEGF165 mediates glomerular endothelial repair [J].

Ostendorf, T ;

Kunter, U ;

Eitner, F ;

Loos, A ;

Regele, H ;

Kerjaschki, D ;

Henninger, DD ;

Janjic, N ;

Floege, J .

JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (07) :913-923

[15] Vascular endothelial growth factor trap in non-small cell lung cancer [J].

Riely, GregoryJ. ;

Miller, Vincent A. .

CLINICAL CANCER RESEARCH, 2007, 13 (15) :4623S-4627S

[16] Proteinuria in a patient receiving anti-VEGF therapy for metastatic renal cell carcinoma [J].

Roncone, Daniel ;

Satoskar, Anjali ;

Nadasdy, Tibor ;

Monk, J. Paul ;

Rovin, Brad H. .

NATURE CLINICAL PRACTICE NEPHROLOGY, 2007, 3 (05) :287-293

[17] Vascular endothelial growth factor (VEGF121) protects rats from renal infarction in thrombotic microangiopathy [J].

Suga, SI ;

Kim, YG ;

Joly, A ;

Puchacz, E ;

Kang, DH ;

Jefferson, JA ;

Abraham, JA ;

Hughes, J ;

Johnson, RJ ;

Schreiner, GF .

KIDNEY INTERNATIONAL, 2001, 60 (04) :1297-1308

[18] Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria [J].

Sugimoto, H ;

Hamano, Y ;

Charytan, D ;

Cosgrove, D ;

Kieran, M ;

Sudhakar, A ;

Kalluri, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (15) :12605-12608

[19] Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: Systematic review and meta-analysis [J].

Zhu, Xiaolei ;

Wu, Shenhong ;

Dahut, William L. ;

Parikh, Chirag R. .

AMERICAN JOURNAL OF KIDNEY DISEASES, 2007, 49 (02) :186-193

← 1 2 →