Endothelin in nondiabetic chronic kidney disease: preclinical and clinical studies

Area of Science:

• Nephrology
• Pharmacology
• Endocrinology

Background:

• Chronic kidney disease (CKD) incidence and prevalence are increasing globally.
• Current therapies for CKD often fail to adequately control blood pressure and proteinuria, leading to progressive renal dysfunction.
• The endothelin (ET) system has emerged as a significant factor in CKD pathogenesis.

Purpose of the Study:

• To review the current literature on the role of the endothelin system in nondiabetic chronic kidney disease.
• To evaluate the therapeutic potential of targeting the ET system for managing CKD progression.

Main Methods:

• Literature review of experimental models and clinical studies.
• Analysis of the involvement of ET-1 and its receptor, endothelin-A, in renal injury.
• Examination of data on endothelin receptor antagonists in slowing CKD progression.

Main Results:

• Experimental models demonstrate ET-1's role in proteinuria, glomerular injury, fibrosis, and inflammation in CKD.
• Endothelin receptor antagonists have shown potential in preclinical and early clinical studies.
• Therapies targeting the ET system may slow CKD progression, primarily by lowering blood pressure and proteinuria.

Conclusions:

• The endothelin system is a critical mediator in the progression of nondiabetic CKD.
• Targeting the endothelin system, specifically endothelin-A receptor antagonism, represents a promising therapeutic strategy.
• Further research and clinical application of ET-targeting therapies are warranted for CKD management.