Abstract: FR-PO399
Combined Dapagliflozin and Eplerenone Treatment Improve Cardiorenal Function in Rats with CKD
Session Information
- Hypertension and CVD: Basic
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Soulié, Matthieu, INSERM U1138, Paris, Île-de-France, France
- Durand, Manon, INSERM U1138, Paris, Île-de-France, France
- Stephan, Yohan, INSERM U1096, Rouen, Normandie, France
- Lima Posada, Ixchel Quetzaliztli, INSERM U1138, Paris, Île-de-France, France
- Palacios Ramirez, Roberto, INSERM U1138, Paris, Île-de-France, France
- Nicol, Lionel, INSERM U1096, Rouen, Normandie, France
- Lopez-Andres, Natalia, Navarrabiomed, Pamplona, Navarra, Spain
- Mulder, Paul, INSERM U1096, Rouen, Normandie, France
- Jaisser, Frederic, INSERM U1138, Paris, Île-de-France, France
Background
Patients with chronic kidney disease (CKD) present higher risk of cardiovascular (CV) complications as well as renal function decline. The DAPA-CKD trial showed reduced CV events in diabetic and non-diabetic CKD patients treated with Dapagliflozine (DAPA). Mineralocorticoid Receptor Antagonists (MRAs) have shown similar beneficial effects in diabetic CKD patients (FIDELIO-CKD & FIGARO-CKD trials) but impact in non-diabetic CKD patients is unkown. The aim of this study was to compare DAPA and Eplerenone (EPLE), alone or in combination on renal and CV functions in a non-diabetic rat CKD model.
Methods
CKD was induced in SD rats by 5/6 nephrectomy. Rats were treated with DAPA (10 mg/kg/day PO), EPLE (100 mg/kg/day PO) or the combination during 3 months after CKD induction before cardiorenal function assessment. Renal impact was assessed by histology and creatinine clearance and 24h albuminuria. Cardiac function was evaluated by cardiac echocardiography and left ventricle (LV) hemodynamics (catheterization). LV perfusion was assessed by Magnetic resonance imaging (MRI).
Results
After 3 month kidney fibrosis is decreased in the 3 treated groups compared to untreated CKD. No changes of creatinine clearance were observed while albuminuria increased in the DAPA groups with no significant effects of EPLE. The fractional shortening and the cardiac output were not modified by the treatments (not shown). Cardiac hemodynamic was improved with reduced LV end diastolic pressure (LVEDP) in the CKD rats treated with EPLE or a combination of EPLE and DAPA while LV end diastolic pressure volume relationship (LVEDPVR) was decrease by both DAPA and EPLE and further decreased by DAPA + EPLE. Decreased cardiac perfusion was prevented with EPLE alone or with the combination.
Conclusion
The use of DAPA + EPLE appears to be more effective than DAPA or EPLE alone on diastolic function in non-diabetic CKD rats while cardiac perfusion is improved by EPLE only.
| Groups | Kidney fibrosis (%) | Creatinine clearance | Albuminuria (mg/24h) | LV perfusion (ml/min/g) | LV EDP (mmHg) | LV EDPVR (mmHg/RVU) |
| CKD | 0.61±0.05 | 3.58±0.53 | 642±128 | 6.07±0.48 | 8.65±0.60 | 3.74±0.18 |
| CKD+DAPA | 0.41±0.06 | 3.61±0.31 | 2170±316* | 7.34±0.49 | 10.41±0.31 | 2.21±0.17* |
| CKD+EPLE | 0.39±0.04 | 4.57±1.49 | 483±141 | 9.31±0.89* | 6.78±0.28* | 2.39±0.21* |
| CKD+DAPA+EPLE | 0.38±0.06* | 3.41±0.41 | 976±268* | 9.40±0.87* | 7.03±0.41* | 1.61±0.15*† |
*: p<0.05 vs CKD, †: p<0.05 vs CKD+DAPA or vs CKD+EPLE