Endothelin antagonists may reduce cardiovascular risk, improve renal hemodynamics, reduce proteinuria, and slow chronic kidney disease progression, potentially synergizing with ACE inhibitors.
Do endothelin antagonists reduce cardiovascular risk and slow disease progression in patients with chronic kidney disease?
Endothelin receptor antagonists represent a promising therapeutic target for reducing cardiovascular risk and slowing disease progression in patients with chronic kidney disease.
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.
Dhaun et al. (Thu,) conducted a review in Chronic Kidney Disease. Endothelin antagonists was evaluated. Endothelin antagonists may reduce cardiovascular risk, improve renal hemodynamics, reduce proteinuria, and slow chronic kidney disease progression, potentially synergizing with ACE inhibitors.