Related Experiment Video
Updated: Apr 30, 2026
A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
Endothelin and endothelin antagonists in chronic kidney disease
Donald E Kohan1, Matthias Barton2
1Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
Insights
Chronic kidney disease (CKD) is increasing globally. Targeting the Endothelin-1 (ET-1) pathway with endothelin receptor antagonists (ERAs) shows promise for treating CKD, potentially beyond current therapies.
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Research
Background:
- Chronic kidney disease (CKD) incidence is rising, with diabetes and hypertension as primary drivers.
- Current treatments, mainly renin-angiotensin system inhibitors, offer limited efficacy in slowing CKD progression.
- Endothelin-1 (ET-1) plays a significant role in renal injury, inflammation, and fibrosis associated with CKD.
Purpose of the Study:
- To review the role of Endothelin-1 (ET-1) in the pathogenesis of chronic kidney disease (CKD).
- To discuss the therapeutic potential of targeting the ET-1 system in CKD management.
- To evaluate the risks and benefits of using endothelin receptor antagonists (ERAs) for CKD.
Main Methods:
- Review of experimental models demonstrating the effects of ERAs on renal injury and fibrosis.
- Analysis of clinical trial data on the antiproteinuric effects of ERAs in CKD patients.
- Summary of the known mechanisms by which ET-1 contributes to CKD.
Main Results:
- ERAs have shown efficacy in ameliorating or reversing renal injury and fibrosis in experimental CKD models.
- Clinical studies indicate significant antiproteinuric effects of ERAs in CKD patients, even with existing renin-angiotensin system blockade.
- ET-1 activation of endothelin A receptors is a key factor in CKD progression.
Conclusions:
- Targeting the ET-1 pathway with ERAs represents a promising therapeutic strategy for CKD.
- ERAs may offer benefits beyond current standard treatments for CKD, particularly in reducing proteinuria.
- Careful consideration of the risk-benefit profile is necessary for clinical application of ERAs in CKD.
Abstract:
The incidence and prevalence of chronic kidney disease (CKD), with diabetes and hypertension accounting for the majority of cases, is on the rise, with up to 160 million individuals worldwide predicted to be affected by 2020. Given that current treatment options, primarily targeted at the renin-angiotensin system, only modestly slow down progression to end-stage renal disease, the urgent need for additional effective therapeutics is evident. Endothelin-1 (ET-1), largely through activation of endothelin A receptors, has been strongly implicated in renal cell injury, proteinuria, inflammation, and fibrosis leading to CKD. Endothelin receptor antagonists (ERAs) have been demonstrated to ameliorate or even reverse renal injury and/or fibrosis in experimental models of CKD, whereas clinical trials indicate a substantial antiproteinuric effect of ERAs in diabetic and nondiabetic CKD patients even on top of maximal renin-angiotensin system blockade. This review summarizes the role of ET in CKD pathogenesis and discusses the potential therapeutic benefit of targeting the ET system in CKD, with attention to the risks and benefits of such an approach.
Related Concept Videos
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:25Antihypertensive Drugs: Direct Renin Inhibitors
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
01:28Chronic Kidney Disease III: Interprofessional Care