The identification of patients at increased risk for chronic kidney disease offers the potential to prevent or delay end-stage renal disease and the associated cardiovascular events. Data from recently completed controlled clinical trials of endothelin (ET) receptor blockers confirmed their potent antiproteinuric effect after a number of preclinical studies. A spectrum of proteinuric glomerular diseases results from podocyte abnormalities and, in return, impact podocyte structure and function. Because podocytes are cells in the glomerulus that form a crucial component of the glomerular filtration barrier, contributing to size selectivity and maintaining a large filtration surface, we focus on evidence that suggest ET-1 may promote podocyte injury thereby aggravating albumin urinary loss and alteration of the glomerular microvasculature. Systematic confrontation of animal models and studies in human subjects should help decipher pathophysiological mechanisms whereby the local renal ET system promotes podocyte injury and chronic kidney disease in specific pathophysiological contexts. Current evidence suggests that more experimental and clinical attention should be paid to conditions with increased vascular or endocapillary ET-1 production on the one hand, and in diseases with altered podocyte phenotype and survival such as focal segmental glomerulosclerosis and crescentic glomerulonephritis on the other. These conclusions may assist clinicians in creating optimal clinical trials for patients at increased risk for or with overt chronic kidney disease.
Copyright © 2011 S. Karger AG, Basel.