title: Systemic and kidney toxicity of intraocular administration of vascular endothelial growth factor inhibitors.
abstract: Intravenous injection of angiogenesis-inhibitor drugs is used widely to treat cancers. Associated renal complications primarily involve proteinuria and hypertension, and thrombotic microangiopathies also have been described. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy currently is used by ophthalmologists to treat neovascularization in age-related macular degeneration. However, there is some evidence that intravitreal anti-VEGF injections may result in systemic absorption, with the potential for injury in organs that are reliant on VEGF, such as the kidney. We report the first case to our knowledge of a patient who developed an acute decrease in kidney function, nonimmune microangiopathic hemolytic anemia with schistocytes, and thrombocytopenia after 4 intravitreal injections of ranibizumab. Light microscopy of a kidney biopsy specimen showed segmental duplications of glomerular basement membranes with endothelial swelling and several recanalized arteriolar thrombi. Because of the increasing use of intravitreal anti-VEGF agents, ophthalmologists and nephrologists should be aware of the associated risk of kidney disease. Early detection is crucial so that intravitreal injections can be stopped before severe kidney disease occurs.
authors.affiliation: Service de néphrologie-transplantation rénale, Hôpital Foch, Suresnes, France. g.pelle@hopital-foch.org
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pellé
authors.forename: Nasim
authors.initials: N
authors.lastname: Shweke
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Duong Van Huyen
authors.forename: Leïla
authors.initials: L
authors.lastname: Tricot
authors.forename: Sadika
authors.initials: S
authors.lastname: Hessaïne
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
authors.forename: Christian
authors.initials: C
authors.lastname: Hiesse
authors.forename: Michel
authors.initials: M
authors.lastname: Delahousse
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D061067:Antibodies, Monoclonal, Humanized; D006801:Humans; D058449:Intravitreal Injections; D007674:Kidney Diseases / Q000139:chemically induced* / Q000175:diagnosis* / Q000378:metabolism; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D000069579:Ranibizumab; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab