title: VEGF inhibition and renal thrombotic microangiopathy.
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.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Vera
authors.initials: V
authors.lastname: Eremina
authors.forename: J Ashley
authors.initials: JA
authors.lastname: Jefferson
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kowalewska
authors.forename: Howard
authors.initials: H
authors.lastname: Hochster
authors.forename: Mark
authors.initials: M
authors.lastname: Haas
authors.forename: Joseph
authors.initials: J
authors.lastname: Weisstuch
authors.forename: Catherine
authors.initials: C
authors.lastname: Richardson
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
authors.forename: M Golam
authors.initials: MG
authors.lastname: Kabir
authors.forename: Peter H
authors.initials: PH
authors.lastname: Backx
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Gerber
authors.forename: Napoleone
authors.initials: N
authors.lastname: Ferrara
authors.forename: Laura
authors.initials: L
authors.lastname: Barisoni
authors.forename: Charles E
authors.initials: CE
authors.lastname: Alpers
authors.forename: Susan E
authors.initials: SE
authors.lastname: Quaggin
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005260:Female; D018390:Gene Targeting; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D050199:Podocytes / Q000378:metabolism*; D011507:Proteinuria / Q000139:chemically induced; D012333:RNA, Messenger / Q000378:metabolism; D012079:Renal Circulation; D015398:Signal Transduction; D013927:Thrombosis / Q000139:chemically induced*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab