EDN1 and focal segmental glomerulosclerosis: Considering the large spectrum of renal actions of AngII and endothelin-1 (ET-1), including vasoconstriction of the afferent and efferent arterioles (AAs and EAs) and mesangial contraction that reduce blood flow and glomerular filtration rate, and their upregulation in kidney injury including FSGS (13), dual inhibition of their actions, as occurs when using sparsentan, is expected to exert multiple actions in many renal cell types and consequently result in a variety of renoprotective mechanisms.