The Non-steroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction In Preclinical Non-diabetic Chronic Kidney Disease

Background: The mineralocorticoid receptor (MR) plays an important role in the development of Chronic Kidney Disease (CKD) and its overactivation contributes to the progression of cardiovascular complications. Antagonizing the overactivation of the MR with MR antagonists (MRA) is a therapeutic option. Finerenone, is a non-steroidal MRA recently studied in two large clinical trials showing the beneficial effects lowering the risks of CKD progression and cardiovascular events in stage 1 to 4 CKD patients with type 2 diabetes (T2D) (FIDELIO-DKD and FIGARO-DKD trials) Aim: To test whether finerenone improves renal and/or cardiac functions in preclinical non-diabetic CKD. Methods: non-diabetic CKD was induced by 5/6 nephrectomy in 6 weeks old Sprague Dawley rats. Finerenone (10 mg/kg/day) was administered as preventive or as curative treatment. Left ventricle (LV) function/hemodynamics, LV tissue perfusion and GFR were assessed in vivo at the age of 24 weeks. Results: 12 weeks after 5/6 nephrectomy, the rats showed classical signs of CKD: reduced GFR and increased kidney weight; associated with LV diastolic dysfunction confirmed by increased in LV end-diastolic pressure (LVEDP), LV relaxation constant (Tau) and LV end-diastolic pressure volume-relation (LVEDPVR), while LV perfusion was reduced. Both prevention and curative treatment with finerenone reduced significantly both LVEDPVR and Tau; and increased LV tissue perfusion. Finerenone treatment did not impact reduced kidney GFR but reduced renal hypertrophy. Conclusion: Both preventive and curative finerenone improves non-diabetic CKD related LV diastolic function, independently from changes in kidney function.