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The oral multitargeted kinase inhibitors (MTKI) sunitinib (SU11248, Sutent; Pfizer, New York) and sorafenib (BAY 43-9006, Nexavar; Bayer Pharmaceuticals, West Haven, CT, and Onyx Pharmaceuticals, Emeryville, CA) are increasingly used to treat malignant solid tumors. These small-molecule agents inhibit signaling through receptor tyrosine kinases such as vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor receptor, and c-KIT, among others (1). In the kidney, glomerular podocytes express VEGF and glomerular endothelial cells express VEGF receptors. Podocyte-specific deletion of a single VEGF allele causes proteinuria and capillary endotheliosis in rodents, and disrupted glomerular VEGF signaling is strongly implicated in the pathogenesis of human preeclampsia (2–4).

journal of the national cancer institute

A Preeclampsia-like Syndrome Characterized by Reversible Hypertension and Proteinuria Induced by the Multitargeted Kinase Inhibitors Sunitinib and Sorafenib