ReviewsThe Endothelin System and Its Antagonism in Chronic Kidney DiseaseDhaun, Neeraj*, †; Goddard, Jane*; Webb, DavidJ.† Author Information *Department of Renal Medicine, Royal Infirmary of Edinburgh, and †Clinical Pharmacology Unit, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, Scotland Address correspondence to: Dr. Neeraj Dhaun, The Queen’s Medical Research Institute, 3rd Floor East, Room E3.23, 47 Little France Crescent, Edinburgh, EH16 4TJ. Phone: +44-131-242-9210; Fax: +44- 870-134-2778; E-mail: [email protected] Journal of the American Society of Nephrology 17(4):p 943-955, April 2006. | DOI: 10.1681/ASN.2005121256 Buy Metrics Abstract The incidence of chronic kidney disease (CKD) is increasing worldwide. Cardiovascular disease (CVD) is strongly associated with CKD and constitutes one of its major causes of morbidity and mortality. Treatments that slow the progression of CKD and improve the cardiovascular risk profile of patients with CKD are needed. The endothelins (ET) are a family of related peptides, of which ET-1 is the most powerful endogenous vasoconstrictor and the predominant isoform in the cardiovascular and renal systems. The ET system has been widely implicated in both CVD and CKD. ET-1 contributes to the pathogenesis and maintenance of hypertension and arterial stiffness and more novel cardiovascular risk factors such as oxidative stress and inflammation. Through these, ET also contributes to endothelial dysfunction and atherosclerosis. By reversal of these effects, ET antagonists may reduce cardiovascular risk. In particular relation to the kidney, antagonism of the ET system may be of benefit in improving renal hemodynamics and reducing proteinuria. ET likely also is involved in progression of renal disease, and data are emerging to suggest a synergistic role for ET receptor antagonists with angiotensin-converting enzyme inhibitors in slowing CKD progression. Copyright © 2006 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.