Effects of Finerenone Combined with Empagliflozin in a Model of Hypertension-Induced End-Organ Damage.

American Journal of Nephrology
Peter KolkhofFrank Eitner

Abstract

The nonsteroidal mineralocorticoid receptor (MR) antagonist finerenone and sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated clinical benefits in CKD patients with type 2 diabetes. Clinical data analyzing the potential value of a combination therapy are currently limited. We therefore investigated cardiorenal protection of respective mono- and combination therapy in a preclinical model of hypertension-induced end-organ damage. Cardiovascular (CV) morbidity and mortality were studied in hypertensive, N(ω)-nitro-L-arginine methyl ester-treated, renin-transgenic (mRen2)27 rats. Rats (10- to 11-week-old females, n = 13-17/group) were treated once daily orally for up to 7 weeks with placebo, finerenone (1 and 3 mg/kg), empagliflozin (3 and 10 mg/kg), or a combination of the respective low doses. Key outcome parameters included mortality, proteinuria, plasma creatinine and uric acid, blood pressure, and cardiac and renal histology. Placebo-treated rats demonstrated a 50% survival rate over the course of 7 weeks. Drug treatment resulted in variable degrees of survival benefit, most prominently in the low-dose combination group with a survival benefit of 93%. Monotherapies of finerenone or empagliflozin dose-dependent...Continue Reading

Citations

Aug 28, 2021·The New England Journal of Medicine·Bertram PittUNKNOWN FIGARO-DKD Investigators
Aug 31, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Peter KolkhofUlrich Kintscher
Sep 15, 2021·Drugs·James E Frampton
Oct 14, 2021·British Journal of Pharmacology·Johann Bauersachs, Natalia López-Andrés

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