Proteinuria and the underlying glomerulosclerosis seem to be reversible. Could such reversal be achieved by targeting endothelin via the ETAreceptor? This Review begins with a summary of the mechanisms involved in the development of glomerulosclerosis—particularly those responsible for podocyte injury—and continues with an evaluation of the growth-promoting and vasoconstricting properties of endothelin. Finally, the findings of preclinical and clinical studies of endothelin receptor antagonists in proteinuric renal disease are summarized.
