Anti-VEGF Therapy Induces Proteinuria through Endothelial Disorganization Leading to Nephrin Decrease in Podocytes

Background: VEGF is involved in cancer development by stimulating neo-angiogenesis and tumor proliferation. Anti-angiogenic therapies, especially tyrosine kinase inhibitors such as sunitinib, have significantly improved cancer prognosis. Nevertheless, renal side effects, such as proteinuria and thrombotic microangiopathy, have been reported. The underlying physiopathological mechanisms remain unclear, but animal models and clinical similarities with preeclampsia suggest that such therapies affect the function of the endothelial and epithelial layers of the glomerular basement membrane, with activation of the endothelin signaling system and loss of glomerular slit diaphragm integrity. The aim of this in vitro study was to determine sunitinib effects on normal podocytes and glomerular endothelial cells.