NOS3 and Renal insufficiency: We have previously shown that podocyte VEGF-A gain-of-function in eNOS KO mice causes massive proteinuria and renal failure (Veron et al., 2014), not unlike those described here in eNOS−/−:VEGFKD + dox mice, illustrating that a relatively narrow range “normal” VEGF-A expression and signaling at the glomerular filtration barrier are required to maintain GFR and selective permeability, as has been previously observed in other genetic and experimental models (Eremina et al., 2008; Sivaskandarajah et al., 2012; Yuen et al., 2012).