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Endothelin Receptor Antagonists in Kidney Disease
Irene Martínez-Díaz1, Nerea Martos1, Carmen Llorens-Cebrià1
1Nephrology and Transplantation Research Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
International Journal of Molecular Sciences
|February 25, 2023
Summary
Endothelin receptor antagonists (ERAs) show promise in slowing kidney disease progression by reducing proteinuria and fibrosis. New strategies, including ETA-specific agents and combinations, aim to mitigate side effects and enhance therapeutic benefits.
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Research
Background:
- Elevated endothelin (ET) levels in kidney disease contribute to vasoconstriction, hyperfiltration, and podocyte damage.
- Endothelin receptor type A (ETA) activation by ET exacerbates kidney injury, leading to proteinuria and declining glomerular filtration rate (GFR).
Purpose of the Study:
- To review the development and therapeutic potential of endothelin receptor antagonists (ERAs) for kidney disease.
- To explore novel strategies for optimizing ERA efficacy and managing adverse events in kidney disease treatment.
Main Methods:
- Review of preclinical and clinical evidence on ERAs in kidney disease.
- Analysis of randomized controlled trials investigating ERA efficacy.
- Examination of emerging therapeutic approaches, including ETA-specific antagonists and combination therapies.
Main Results:
- ERAs have demonstrated efficacy in reducing kidney fibrosis, inflammation, and proteinuria in preclinical and clinical studies.
- Some ERAs faced commercialization challenges due to adverse events, primarily edema.
- ETA-specific antagonists and combination therapies (e.g., with SGLT2 inhibitors) are being investigated to improve safety profiles.
Conclusions:
- ERAs represent a promising therapeutic class for managing kidney disease, offering protection against fibrosis and proteinuria.
- Targeting ETA specifically and exploring combination therapies are key strategies to enhance the therapeutic window of ERAs.
- Further research and clinical trials are essential to establish the optimal use of ERAs and novel therapeutic combinations in kidney disease management.
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