Endothelin receptor antagonists for the treatment of diabetic and nondiabetic chronic kidney disease

Curr Opin Nephrol Hypertens. 2021 Jul 1;30(4):456-465. doi: 10.1097/MNH.0000000000000716.


Purpose of review: To summarize new clinical findings of endothelin receptor antagonists (ERA) in various etiologies of kidney disease targeted in clinical trials.

Recent findings: Endothelin-1 is a multifunctional peptide with potential relevance to glomerular and tubulointerstitial kidney diseases. The phase 3 SONAR trial demonstrated a significant reduction in clinically relevant kidney outcomes for patients with diabetic kidney disease (DKD) after long-term treatment with the ERA, atrasentan, in addition to blockade of the renin-angiotensin-aldosterone system. Promising preclinical disease models and small clinical trials in non-DKD resulted in the initiation of phase 3 trials investigating the effects of long-term treatment with ERA in patients with immunoglobulin A (IgA) nephropathy and focal segmental glomeruloscelerosis (FSGS). The mechanisms by which ERA protects the kidneys have been extensively studied with evidence for the protection of tubule cells, podocytes, mesangial cells, the endothelial glycocalyx, and a reduction in glomerular perfusion pressure. The occurrence of fluid retention during ERA treatment, particularly in susceptible populations, necessitates strategies to support safe and effective treatment.

Summary: Treatment with ERA induces long-term kidney protection in DKD. Phase 3 trials are underway to investigate ERA effects in patients with IgA nephropathy and FSGS.

Trial registration: ClinicalTrials.gov NCT04724837.

Publication types

  • Review

MeSH terms

  • Atrasentan
  • Diabetes Mellitus*
  • Diabetic Nephropathies* / drug therapy
  • Endothelin Receptor Antagonists / therapeutic use
  • Humans
  • Renal Insufficiency, Chronic* / drug therapy
  • Renin-Angiotensin System


  • Endothelin Receptor Antagonists
  • Atrasentan

Associated data

  • ClinicalTrials.gov/NCT04724837