VEGF Inhibition and Renal Thrombotic Microangiopathy
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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.
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The record
- Venue
- New England Journal of Medicine
- Topic
- Renal Diseases and Glomerulopathies
- Field
- Medicine
- Canadian institutions
- St. Michael's HospitalHeart and Stroke FoundationUniversity of TorontoToronto General HospitalLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
- Funders
- Canadian Institutes of Health Research
- Keywords
- Thrombotic microangiopathyMedicineBevacizumabMicroangiopathyPathogenesisVascular endothelial growth factorKidney diseaseKidneyAcute kidney injuryInternal medicinePathologyVEGF receptorsEndocrinologyDiseaseChemotherapyDiabetes mellitus
- Has abstract in OpenAlex
- yes