Endothelin Receptor Antagonists in Kidney Disease.
Int J Mol Sci
; 24(4)2023 Feb 08.
Article
de En
| MEDLINE
| ID: mdl-36834836
ABSTRACT
Endothelin (ET) is found to be increased in kidney disease secondary to hyperglycaemia, hypertension, acidosis, and the presence of insulin or proinflammatory cytokines. In this context, ET, via the endothelin receptor type A (ETA) activation, causes sustained vasoconstriction of the afferent arterioles that produces deleterious effects such as hyperfiltration, podocyte damage, proteinuria and, eventually, GFR decline. Therefore, endothelin receptor antagonists (ERAs) have been proposed as a therapeutic strategy to reduce proteinuria and slow the progression of kidney disease. Preclinical and clinical evidence has revealed that the administration of ERAs reduces kidney fibrosis, inflammation and proteinuria. Currently, the efficacy of many ERAs to treat kidney disease is being tested in randomized controlled trials; however, some of these, such as avosentan and atrasentan, were not commercialized due to the adverse events related to their use. Therefore, to take advantage of the protective properties of the ERAs, the use of ETA receptor-specific antagonists and/or combining them with sodium-glucose cotransporter 2 inhibitors (SGLT2i) has been proposed to prevent oedemas, the main ERAs-related deleterious effect. The use of a dual angiotensin-II type 1/endothelin receptor blocker (sparsentan) is also being evaluated to treat kidney disease. Here, we reviewed the main ERAs developed and the preclinical and clinical evidence of their kidney-protective effects. Additionally, we provided an overview of new strategies that have been proposed to integrate ERAs in kidney disease treatment.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Antagonistes des récepteurs de l'endothéline
/
Maladies du rein
Type d'étude:
Clinical_trials
Limites:
Humans
Langue:
En
Journal:
Int J Mol Sci
Année:
2023
Type de document:
Article
Pays d'affiliation:
Espagne