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

Pediatr Nephrol. 2021 Apr;36(4):763-775. doi: 10.1007/s00467-020-04518-2. Epub 2020 Mar 17.

Abstract

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.

Keywords: Endothelin receptor antagonist; Kidney disease; Renin-angiotensin system inhibition.

Publication types

  • Review

MeSH terms

  • Endothelin Receptor Antagonists / metabolism
  • Endothelin Receptor Antagonists / therapeutic use
  • Endothelins / metabolism
  • Humans
  • Kidney / metabolism
  • Renal Insufficiency, Chronic* / drug therapy
  • Renal Insufficiency, Chronic* / metabolism
  • Renin-Angiotensin System*

Substances

  • Endothelin Receptor Antagonists
  • Endothelins