Endothelin Receptor Antagonists in Kidney Disease
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 (ET<sub>A</sub>) activation, causes sustained vasoconstriction...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3427 |
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| author | Irene Martínez-Díaz Nerea Martos Carmen Llorens-Cebrià Francisco J. Álvarez Patricia W. Bedard Ander Vergara Conxita Jacobs-Cachá Maria José Soler |
| author_facet | Irene Martínez-Díaz Nerea Martos Carmen Llorens-Cebrià Francisco J. Álvarez Patricia W. Bedard Ander Vergara Conxita Jacobs-Cachá Maria José Soler |
| author_sort | Irene Martínez-Díaz |
| collection | DOAJ |
| description | 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 (ET<sub>A</sub>) 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 ET<sub>A</sub> 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. |
| first_indexed | 2024-03-11T08:42:41Z |
| format | Article |
| id | doaj.art-25d2a4b82b8746859952b6ee455af496 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:42:41Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-25d2a4b82b8746859952b6ee455af4962023-11-16T20:59:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244342710.3390/ijms24043427Endothelin Receptor Antagonists in Kidney DiseaseIrene Martínez-Díaz0Nerea Martos1Carmen Llorens-Cebrià2Francisco J. Álvarez3Patricia W. Bedard4Ander Vergara5Conxita Jacobs-Cachá6Maria José Soler7Nephrology 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, SpainNephrology 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, SpainNephrology 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, SpainTravere Therapeutics, Inc., San Diego, CA 92130, USATravere Therapeutics, Inc., San Diego, CA 92130, USANephrology 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, SpainNephrology 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, SpainNephrology 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, SpainEndothelin (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 (ET<sub>A</sub>) 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 ET<sub>A</sub> 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.https://www.mdpi.com/1422-0067/24/4/3427endothelinendothelin receptor antagonists (ERAs)atrasentansparsentankidney disease |
| spellingShingle | Irene Martínez-Díaz Nerea Martos Carmen Llorens-Cebrià Francisco J. Álvarez Patricia W. Bedard Ander Vergara Conxita Jacobs-Cachá Maria José Soler Endothelin Receptor Antagonists in Kidney Disease International Journal of Molecular Sciences endothelin endothelin receptor antagonists (ERAs) atrasentan sparsentan kidney disease |
| title | Endothelin Receptor Antagonists in Kidney Disease |
| title_full | Endothelin Receptor Antagonists in Kidney Disease |
| title_fullStr | Endothelin Receptor Antagonists in Kidney Disease |
| title_full_unstemmed | Endothelin Receptor Antagonists in Kidney Disease |
| title_short | Endothelin Receptor Antagonists in Kidney Disease |
| title_sort | endothelin receptor antagonists in kidney disease |
| topic | endothelin endothelin receptor antagonists (ERAs) atrasentan sparsentan kidney disease |
| url | https://www.mdpi.com/1422-0067/24/4/3427 |
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