ArticleInternational journal of molecular sciences2022
Enhanced Cardiorenal Protective Effects of Combining SGLT2 Inhibition, Endothelin Receptor Antagonism and RAS Blockade in Type 2 Diabetic Mice.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Efficacy and safety of endothelin receptor antagonists in non-diabetic kidney nephropathy : A systematic review and meta-analysis.Wiener klinische Wochenschrift · 2025Pooled it
- Comparative efficacy and safety of different SGLT2 inhibitor-based combination strategies in HFrEF: a systematic review and network meta-analysis.Frontiers in endocrinology · 2025Pooled it
- Effects of Empagliflozin Combined with Anaerobic, Aerobic, and Endurance Swimming Protocols on Cardiac Structure and Electrophysiology in Healthy Rats.Journal of clinical medicine · 2026Article
- Progress in mechanistic and clinical translational research of endothelin A receptor antagonists in the treatment of diabetic kidney disease: a narrative review.Frontiers in endocrinology · 2026Review
- The role of endothelin receptor antagonists in kidney disease.Renal failure · 2025Review
- Obesity-Related Kidney Disease: A Growing Threat to Renal Health.International journal of molecular sciences · 2025Review
- Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular-Kidney-Metabolic (CKM) Syndrome.Antioxidants (Basel, Switzerland) · 2025Review
- Endothelin receptor antagonists in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- SGLT2 inhibitors: how do they affect the cardiac cells.Molecular and cellular biochemistry · 2025Review
- Combination therapy as a new standard of care in diabetic and non-diabetic chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Combination therapy for kidney disease in people with diabetes mellitus.Nature reviews. Nephrology · 2024Review
- Renal antiporter ClC-5 regulates collagen I/IV through the β-catenin pathway and lysosomal degradation.Life science alliance · 2024Article
- SGLT2i and GLP1-RA exert additive cardiorenal protection with a RAS blocker in uninephrectomized db/db mice.Frontiers in pharmacology · 2024Article
- The sodium glucose co-transporter 2 inhibitor dapagliflozin ameliorates the fluid-retaining effect of the endothelin A receptor antagonist zibotentan.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- The Role of Renin-Angiotensin System in Diabetic Cardiomyopathy: A Narrative Review.Life (Basel, Switzerland) · 2023Review
- Endothelin-1, Outcomes in Patients With Heart Failure and Reduced Ejection Fraction, and Effects of Dapagliflozin: Findings From DAPA-HF.Circulation · 2023Article
- Novel Aspects of the Immune Response Involved in the Peritoneal Damage in Chronic Kidney Disease Patients under Dialysis.International journal of molecular sciences · 2023Review
- Endothelin Receptor Antagonists in Kidney Disease.International journal of molecular sciences · 2023Review
- Niaoduqing alleviates podocyte injury in high glucose modelFrontiers in pharmacology · 2023Article
- Cardiorenal syndrome and diabetes: an evil pairing.Frontiers in cardiovascular medicine · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Treatments with sodium-glucose 2 cotransporter inhibitors (SGLT2i) or endothelin receptor antagonists (ERA) have shown cardiorenal protective effects. The present study aimed to evaluate the cardiorenal beneficial effects of the combination of SGLT2i and ERA on top of renin-angiotensin system (RAS) blockade. Type 2 diabetic mice (db/db) were treated with different combinations of an SGLT2i (empagliflozin), an ERA (atrasentan), and an angiotensin-converting enzyme inhibitor (ramipril) for 8 weeks. Vehicle-treated diabetic mice and non-diabetic mice were included as controls. Weight, blood glucose, blood pressure, and kidney and heart function were monitored during the study. Kidneys and heart were collected for histological examination and to study the intrarenal RAS. Treatment with empagliflozin alone or combined significantly decreased blood glucose compared to vehicle-treated db/db. The dual and triple therapies achieved significantly greater reductions in diastolic blood pressure than ramipril alone. Compared to vehicle-treated db/db, empagliflozin combined with ramipril or in triple therapy significantly prevented GFR increase, but only the triple combination exerted greater protection against podocyte loss. In the heart, empagliflozin alone or combined reduced cardiac isovolumetric relaxation time (IVRT) and left atrium (LA) diameter as compared to vehicle-treated db/db. However, only the triple therapy was able to reduce cardiomyocyte area. Importantly, the add-on triple therapy further enhanced the intrarenal ACE2/Ang(1-7)/Mas protective arm of the RAS. These data suggest that triple therapy with empagliflozin, atrasentan and ramipril show synergistic cardiorenal protective effects in a type 2 diabetic mouse model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.