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Abstract: SA-PO424

Non-Steroidal Mineralocorticoid Receptor Antagonists (MRAs)-Finerenone Ameliorates Mitochondrial Dysfunction via PI3K/Akt Signaling Pathway in Diabetic Tubulopathy

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic

Author

  • Wang, Pei, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Background

Diabetic tubulopathy (DT) is gradually valued and elucidated as same as glomerular pathology in the pathophysiological perturbations of diabetic kidney disease (DKD). The mitochondria-centric view of DT is emerging as a vital pathological factor in metabolic diseases including DKD. Finerenone (FIN), a novel non-steroidal MRAs, attenuates proteinuria and fibrosis in tubules in DM, but these precise pathomechanisms remain unclear.

Methods

We investigated the role of mineralocorticoid receptor (MR) activation in perturbation of mitochondrial function via PI3K/Akt signaling pathway, including mitochondrial dynamics and mitophagy, under a DM state or hyperglycemia ambience.

Results

In vivo, the molecules were examined in kidneys of DM and FIN treatment mice as well. Notably, FIN administration partially attenuated mitochondrial fragmentation, oxidative stress, and apoptosis and restored mitophagy via PI3K/Akt signaling pathway both in HK-2 cells subjected to HG ambience and tubular cells of DM mice.

Conclusion

These results suggest a novel mechanism linking MR activation to mitochondrial dysfunction via PI3K/Akt signaling pathway during tubular injury in the pathogenesis of DKD and it provides evidence support for FIN as a agent for the treatment of DKD.