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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.
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1 Sorbonne Université, Université Paris Cité, INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Normandie Univ, UNIROUEN, INSERM U1096, Rouen, France (GRID:grid.460771.3) (ISNI:0000 0004 1785 9671)
2 Normandie Univ, UNIROUEN, INSERM U1096, Rouen, France (GRID:grid.460771.3) (ISNI:0000 0004 1785 9671)
3 Sorbonne Université, Université Paris Cité, INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602)
4 Universidad Pública de Navarra (UPNA), Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Pamplona, Spain (GRID:grid.410476.0) (ISNI:0000 0001 2174 6440)
5 Sorbonne Université, Université Paris Cité, INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Université de Lorraine, INSERM Centre d’Investigations Cliniques-Plurithématique 1433, UMR 1116, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT, Nancy, France (GRID:grid.29172.3f) (ISNI:0000 0001 2194 6418)