Journal
AMERICAN JOURNAL OF NEPHROLOGY
Volume 53, Issue 7, Pages 552-564Publisher
KARGER
DOI: 10.1159/000524940
Keywords
Mineralocorticoid receptor antagonist; Finerenone; Aldosterone; Chronic kidney disease
Categories
Funding
- Bayer Pharma AG, Germany
- DZHK [BER 5.4 PR]
- Deutsche For-schungsgemeinschaft [DFG-KI 712/10-1, SFB-1470-A09, WE 1688 19-1]
- Einstein Foundation/Foundation Charite [EVF-BIH-2018-440]
- Deutsche For-schungsgemeinschaft (DFG) [ID470188766]
- [BfR1328-564]
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This study investigated the anti-inflammatory/fibrotic and immunological effects of the nonsteroidal MR antagonist finerenone in a cardiorenal disease model. The results showed that finerenone could alleviate cardiorenal damage, reduce blood pressure, decrease renal inflammatory cell content, and improve cardiac function.
Introduction: Chronic activation of the mineralocorticoid receptor (MR) leads to pathological processes like inflammation and fibrosis during cardiorenal disease. Modulation of immunological processes in the heart or kidney may serve as a mechanistic and therapeutic interface in cardiorenal pathologies. In this study, we investigated anti-inflammatory/-fibrotic and immunological effects of the selective nonsteroidal MR antagonists finerenone (FIN) in the deoxycorticosterone acetate (DOCA)-salt model. Methods: Male C57BL6/J mice were uninephrectomized and received a DOCA pellet implantation (2.4 mg/day) plus 0.9% NaCl in drinking water (DOCA-salt) or received a sham operation and were orally treated with FIN (10 mg/kg/day) or vehicle in a preventive study design. Five weeks after the procedure, blood pressure (BP), urinary albumin/creatinine ratio (UACR), glomerular and tubulointerstitial damage, echocardiographic cardiac function, as well as cardiac/renal inflammatory cell content by FACS analysis were assessed. Results: BP was significantly reduced by FIN. FACS analysis revealed a notable immune response due to DOCA-salt exposure. Especially, infiltrating renal ROR gamma t gamma delta-positive T cells were upregulated, which was significantly ameliorated by FIN treatment. This was accompanied by a significant reduction of UACR in FIN-treated mice. In the heart, FIN reduced DOCA-salt-induced cardiac hypertrophy, cardiac fibrosis and led to an improvement of the global longitudinal strain. Cardiac actions of FIN were not associated with a regulation of cardiac ROR gamma t gamma delta-positive T cells. Discussion/Conclusion: The present study shows cardiac and renal protective effects of FIN in a DOCA-salt model. The cardiorenal protection was accompanied by a reduction of renal ROR gamma t gamma delta T cells. The observed actions of FIN may provide a potential mechanism of its efficacy recently observed in clinical trials.
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