Endothelin-targeted new treatments for proteinuric and inflammatory glomerular diseases: focus on the added value to anti-renin-angiotensin system inhibition

Chronic kidney disease (CKD) is the main cause of end-stage renal disease worldwide arising as a frequent complication of diabetes, obesity, and hypertension. Current therapeutic options, mainly based of inhibition of the renin-angiotensin system (RAS), provide imperfect renoprotection if started at an advanced phase of the disease, and treatments that show or even reverse the progression of CKD are needed. The endothelin (ET) system contributes to the normal renal physiology; however, robust evidence suggests a key role of ET-1 and its cognate receptors, in the progression of CKD. The effectiveness of ET receptor antagonists in ameliorating renal hemodynamics and fibrosis has been largely demonstrated in different experimental models. A significant antiproteinuric effect of ET receptor antagonists has been found in diabetic and non-diabetic CKD patients even on top of RAS blockade, and emerging evidence from ongoing clinical trials highlights their beneficial effects on a wide range of kidney disorders.

Automated summary

Chronic kidney disease is a leading cause of end-stage renal disease globally, often associated with diabetes, obesity, and hypertension. The endothelin system plays a key role in the progression of CKD, with evidence supporting the effectiveness of ET receptor antagonists in improving renal function and fibrosis. Clinical trials have shown beneficial effects of these antagonists on a wide range of kidney disorders.