Academic Journal
Benefit of combination therapy with dapagliflozin and eplerenone on cardiac function and fibrosis in rats with non-diabetic chronic kidney disease
| Title: | Benefit of combination therapy with dapagliflozin and eplerenone on cardiac function and fibrosis in rats with non-diabetic chronic kidney disease |
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| Authors: | M. Soulié, Y. Stephan, M. Durand, I. Lima-Posada, R. Palacios-Ramírez, L. Nicol, N. Lopez-Andres, P. Mulder, F. Jaisser |
| Source: | Scientific Reports, Vol 14, Iss 1, Pp 1-10 (2024) |
| Publisher Information: | Nature Portfolio, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Cardiorenal, Chronic kidney disease, Mineralocorticoid receptor antagonist, Sodium-glucose cotransporter-2 inhibitor, 5/6 nephrectomy, Medicine, Science |
| More Details: | Abstract Patients with chronic kidney disease (CKD) are at a high risk of cardiovascular (CV) complications. In these patients, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce CV events. Mineralocorticoid receptor antagonists (MRAs) exert similar benefits in diabetic CKD, though their effects in non-diabetic CKD remain unclear. This study aimed to evaluated whether the combination of Dapagliflozin (DAPA) and Eplerenone (EPLE) would have positive effects on cardiorenal functions in a non-diabetic CKD model. CKD was induced in rats via 5/6 nephrectomy, followed by treatment with DAPA (5 mg/kg/day PO), EPLE (100 mg/kg/day PO) or the combination for 3 months following CKD induction. Cardiorenal functions were assessed after the treatment period. All treated groups showed reduced kidney fibrosis though plasma creatinine and urea levels remained unchanged. Compared to untreated CKD, EPLE or DAPA/EPLE reduced left ventricle (LV) end-diastolic pressure and LV end-diastolic pressure volume relationship, whereas DAPA alone did not achieve significant reductions. Compared to untreated CKD, EPLE and DAPA/EPLE improved cardiac perfusion but DAPA alone did not. Cardiac fibrosis in CKD was blunted by either DAPA or EPLE alone, with the combination showing an additive effect. In conclusion, co-treatment with DAPA and EPLE enhances diastolic function, cardiac perfusion and reduces myocardial fibrosis in non-diabetic CKD rats. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-024-74934-z |
| Access URL: | https://doaj.org/article/15f1b047b07849c4b85225bbf161495d |
| Accession Number: | edsdoj.15f1b047b07849c4b85225bbf161495d |
| Database: | Directory of Open Access Journals |
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| ISSN: | 20452322 |
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| DOI: | 10.1038/s41598-024-74934-z |
| Published in: | Scientific Reports |
| Language: | English |