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Abstract: FR-PO327

Mineralocorticoid Receptor Antagonism by Finerenone Improves Diastolic Dysfunction Induced by CKD in Mice

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Bonnard, Benjamin, INSERM U1138, Paris Cedex 13, France
  • Pieronne-Deperrois, Marie, INSERM 1096, Paris, France
  • Djerada, Zoubir, INSERM 1096, Paris, France
  • El moghrabi, Soumaya, INSERM U1138, Paris Cedex 13, France
  • Kolkhof, Peter, BAYER AG, Wuppertal, Germany
  • Ouvrard-Pascaud, Antoine, INSERM 1096, Paris, France
  • Mulder, Paul, INSERM 1096, Paris, France
  • Jaisser, Frederic, INSERM U1138, Paris Cedex 13, France
  • Messaoudi, Smail, INSERM U1138, Paris Cedex 13, France
Background

Managing the cardiovascular complications of renal failure is a major therapeutic challenge in clinical practice. Mineralocorticoid Receptor (MR) blockade is a highly effective strategy for the management of heart failure, but the use of MR antagonists (MRA) is limited by their side effects rendering them contraindicated in patients with renal failure. Finerenone is a new non-steroidal MRA that has demonstrated in more than 2000 patients with heart failure and additional chronic kidney disease (CKD) as well as in patients with diabetic kidney disease that neither hyperkalemia nor reductions in kidney function were limiting factors to its use.
The aim of this study is to characterize the effects of finerenone on the cardiac complications of renal failure in a mouse model of CKD.

Methods

CKD was induced by subtotal nephrectomy (Nx), and finerenone was administered at a low dose (2.5 mg/kg/d) from week 4 to week 10 post-Nx. Cardiac function was assessed by echocardiography and invasive hemodynamic while cardiac fibrosis was measured by Sirius Red staining.

Results

Renal failure induced cardiac systolic and diastolic dysfunctions as well as minor changes on cardiac structure in untreated CKD mice. We also observed alterations in the phosphorylation of proteins playing key roles in the calcium handling (phospholamban, calmodulin kinase II) in these mice. Finerenone prevented most of these lesions without interfering with renal dysfunction.

Conclusion

The benefits of finerenone suggest that MR plays a key role in the development of diastolic dysfunction induced by CKD, thus providing a rationale for further clinical studies with MRAs in patients with CKD.

Funding

  • Commercial Support