Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors.

The non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone (FIN) improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) in type 2 diabetes (T2D). We explored the effect of FIN in a novel model of type 1 diabetic Munich Wistar Frömter (MWF) rat (D) induced by injection of streptozotocin (15 mg/kg) and additional exposure to a high-fat/high-sucrose diet. Oral treatment with FIN (10 mg/kg/day in rat chow) in diabetic animals (D -FIN) was compared to a group of D rats receiving no treatment and a group of non-diabetic untreated MWF rats (C) (n = 7–10 animals per group). After 6 weeks, D and D -FIN exhibited significantly elevated blood glucose levels (271.7 ± 67.1 mg/dl and 266.3 ± 46.8 mg/dl) as compared to C (110.3 ± 4.4 mg/dl; p < 0.05). D showed a 10-fold increase of kidney damage markers Kim-1 and Ngal which was significantly suppressed in D -FIN. Blood pressure, pulse wave velocity (PWV) and arterial collagen deposition were lower in D -FIN, associated to an improvement in endothelial function due to a reduction in pro-contractile prostaglandins, as well as reactive oxygen species (ROS) and inflammatory cytokines (IL-1, IL-6, TNFα and TGFβ) in perivascular and perirenal adipose tissue (PVAT and PRAT, respectively). In addition, FIN restored the imbalance observed in CKD between the procalcifying BMP-2 and the nephroprotective BMP-7 in plasma, kidney, PVAT, and PRAT. Our data show that treatment with FIN improves kidney and vascular damage in a new rat model of DKD with T1D associated with a reduction in inflammation, fibrosis and osteogenic factors independently from changes in glucose homeostasis. [Display omitted] • FIN has a protective effect on kidney and cardiovascular damage progression in a new model of T1DM in established CKD. • FIN reduces kidney damage markers, blood pressure, vascular prostanoids, ROS and collagen content, PWV and heart weight. • FIN prevents diabetes-induced upregulation of proinflammatory, profibrotic, and osteogenic factors in PVAT and PRAT. • FIN restores the imbalance between procalcifying BMP-2 and nephroprotective BMP-7 in plasma, kidney, PVAT, and PRAT. • All beneficial effects of FIN are observed despite no change in glycaemia or other characteristic symptoms of diabetes. • These results support further studies exploring the therapeutic potential of FIN on kidney and vascular damage in T1DM. [ABSTRACT FROM AUTHOR]