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Abstract: PO0687

The Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Left Ventricular Function in Preclinical Diabetic CKD

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Lima Posada, Ixchel Quetzaliztli, Centre de Recherche des Cordeliers, INSERM 1138, París, France
  • Stephan, Yohan, Normandy University, INSERM U1096, Rouen, France
  • Soulié, Matthieu, Normandy University, INSERM U1096, Rouen, France
  • Bonnard, Benjamin, Centre de Recherche des Cordeliers, INSERM 1138, París, France
  • Palacios Ramirez, Roberto, Centre de Recherche des Cordeliers, INSERM 1138, París, France
  • Nicol, Lionel, Normandy University, INSERM U1096, Rouen, France
  • Kolkhof, Peter, Bayer AG, R&D Pharmaceuticals, Cardiovascular Research, Wuppertal, Germany
  • Mulder, Paul, Normandy University, INSERM U1096, Rouen, France
  • Jaisser, Frederic, Centre de Recherche des Cordeliers, INSERM 1138, París, France

Group or Team Name

  • Diabetes, metabolic diseases and comorbidities
Background

The steroidal MR antagonist (MRA) spironolactone and eplerenone reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF) but their use in patients with CKD is not indicated due to the associated risk of hyperkalemia. Finerenone is a non-steroidal MRA which recently reduced the composite kidney and cardiovascular outcomes in the phase III study FIDELIO in CKD patients with T2D.
Purpose: To test whether finerenone improves renal and cardiac function in preclinical CKD rat models with T2D.

Methods

12 weeks old male Zucker Diabetic rats (ZSF1) were used as model of diabetic CKD. Finerenone was administered at the dose of 10 mg/kg/d po. GFR (transcutaneous FITC-sinistrin) and cardiac LV function/hemodynamics (LV catheterization) and LV tissue perfusion (MRI) were assessed in vivo at the age of 24 weeks.

Results

24-week old ZSF1 rats showed classical signs of CKD, with reduced GFR (1.44±0.11 ml/min/100g body weight for non-diabetic rats vs 1.04±0.16 ml/min/100g body weight for ZSF1, p<0.05). This was associated with LV diastolic dysfunction, illustrated by the increases in LV end-diastolic pressure (LVEDP; 5.58±0.57 vs. 8.04±0.81 mmHg, p<0.05), and LV end-diastolic pressure volume-relation (LVEDPVR; 1.10±0.23 vs. 5.63±0.54 mmHg/relative volume unit, p<0.05) without significant changes in LV end-systolic pressure (LVESP; 173±10 vs 197±5 mmHg) or LV end-systolic pressure volume-relation (LVESPVR; 32.7±4.2 vs 28.2±1.09 mmHg/relative volume unit). LV perfusion was reduced (5.21±0.37 vs 4.11±0.21 ml/min/g LV tissue; p<0.05).
Finerenone treatment did not impact GFR in ZSF1 rats (0.93±0.17 ml/min/100g body weight) but reduced significantly LVEDP (5.72±0.76 mmHg, p<0.05) and LV end-diastolic pressure volume-relation (LVEDPVR; 2.73±0.33 mmHg/relative volume unit; p<0.05). Finerenone increased LV tissue perfusion (6.90±0.34 ml/min/g LV tissue).

Conclusion

Finerenone treatment improves CKD related LV diastolic function in diabetic CKD rats, independently from changes in GFR.

Funding

  • Commercial Support –