A Nonsteroidal Mineralocorticoid Receptor Antagonist Alleviates Vascular Aging in CKD

Background: Chronic kidney disease (CKD) is associated with early vascular aging processes, leading to increased morbidity and mortality. Aldosterone may exacerbate these processes, but the impact of mineralocorticoid receptor blocking on vascular complications in CKD remains unknown. This study aims to assess the impact of a novel nonsteroidal mineralocorticoid receptor antagonist, finerenone, on mitigating vascular aging in CKD. Methods: CKD was induced in mice using an adenine-rich diet. Three groups of C57BL/6 mice were assigned to distinct dietary regimens: standard chow, a diet enriched with 0.25% adenine, and an adenine-enriched diet supplemented with finerenone (10 mg/kg) (n=6, 14, and 14, respectively). After a 6-week diet, renal function was assessed by serum creatinine and urine albumin levels. Vascular aging and calcification were studied on the aorta ex vivo to evaluate the effects of adenine and finerenone. (Figure) Results: The adenine diet increased serum creatinine levels and urine albumin-to-creatinine ratios, but finerenone treatment improved these measures. Alkaline phosphatase levels in serum and calcium deposits in the aorta increased in mice fed adenine but normalized in the adenine/finerenone group. Whereas, serum aldosterone levels were upregulated in both adenine and adenine/finerenone groups compared to control mice. Aortic expressions of senescence and SASP markers Cdkn1a, Tnfα, and Serpine1 increased in the adenine group but decreased with finerenone treatment. Finerenone also improved the expression of the osteogenic marker Sox9 in the aorta, correlating with Cdkn1a expressions. Conclusion: CKD triggers osteogenic changes and vascular aging in a murine model, but finerenone mitigates vascular aging, at least partly due to the improvement of Sox9 expression. These findings support the exploration of mineralocorticoid receptor blocking strategies for improving vascular aging in CKD.