Endothelin in chronic proteinuric kidney disease

Abstract

The incidence of chronic kidney diseases is increasing worldwide at an alarming rate. As this is emerging as a global threat to human health, present efforts are concentrated on the identification of new treatments that slow or even reverse the progression of chronic nephropathies. Endothelin (ET)-1 is a potent vasoconstrictor peptide with proinflammatory, mitogenic, and profibrotic effects, and it contributes to both normal renal physiology and pathology. There is robust experimental and clinical evidence for the role of ET-1and its cognate receptors in many progressive renal disorders. The effectiveness of ET receptor antagonists in improving renal hemodynamics and reducing fibrosis has been largely documented in experimental animals. However, whether selective ET(A) or dual ET(A)/ET(B) receptor antagonists are preferable is still a matter of debate. Combined therapies, including ET receptor antagonists, are promising to maximize partial renoprotection achieved with blockade of the renin-angiotensin system, particularly when treatment is given in the latter phase of the disease. The focus of this review is to explore the role of ET-1 in kidney diseases and to shed light on the novel pharmacological setting in chronic nephropathies.