Endothelin receptor antagonists in kidney protection for diabetic kidney disease and beyond?

The burden of chronic kidney disease is increasing worldwide, largely due to the increasing global prevalence of diabetes mellitus and hypertension. While renin angiotensin system inhibitors and sodium-glucose cotransporter two inhibitors are the management cornerstone for reducing kidney and cardiovascular complications in patients with diabetic and non-diabetic kidney disease (DKD), they are partially effective and further treatments are needed to prevent the progression to kidney failure. Endothelin receptor antagonism represent a potential additional therapeutic option due to its beneficial effect on pathophysiological processes involved in progressive kidney disease including proteinuria, which are independently associated with progression of kidney disease. This review discusses the biological mechanisms of endothelin receptor antagonists (ERA) in kidney protection, the efficacy and safety of ERA in randomised controlled trials reporting on kidney outcomes, and its potential future use in both diabetic and non-DKDs.