Non-steroid Mineralocorticoid Receptor Antagonist Finerenone Improves Diabetic Kidney Disease Through Inhibiting Ferroptosis of Renal Tubule

Non-steroid Mineralocorticoid Receptor Antagonist Finerenone Improves Diabetic Kidney Disease Through Inhibiting Ferroptosis of Renal Tubule | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 28 October 2025 V1 Latest version Share on Non-steroid Mineralocorticoid Receptor Antagonist Finerenone Improves Diabetic Kidney Disease Through Inhibiting Ferroptosis of Renal Tubule Authors : Mingyan Zhang , Shanpan Fu , Yuemei Xi , Qiang Wang , De Xie , Junliang He , Linqian Yu , … Show All … , Qian Zhang , Jiayu Chen , Liushuang Xu , Yayan Liu , Xueling Ye , Mengni Wu , Wanling Que , Shuyi Chen , Shuai Huang , Cuiying Ye , Tetsuya Yamamoto , Hidenori Koyama , jidong Cheng [email protected] , and Yanhui Wu Show Fewer Authors Info & Affiliations https://doi.org/10.22541/au.176165565.56119616/v1 158 views 96 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background and Purpose: Diabetic kidney disease (DKD) is a major complication of diabetes, primarily linked to glomerular damage. However, recent research has highlighted the importance of renal tubular injury in DKD progression. Finerenone (FIN), a non-steroidal mineralocorticoid receptor (MR) antagonist, has shown promise as a treatment for DKD. Ferroptosis, an iron-dependent form of cell death, plays a significant role in DKD progression. This study investigates whether FIN can mitigate renal tubular ferroptosis and explore the underlying mechanisms involved. Experimental Approach: We evaluated the effects of FIN in two diabetic mouse models: high-fat diet (HFD)-streptozotocin (STZ) and db/db mice. Renal function, injury, and fibrosis were assessed, along with markers of ferroptosis, iron metabolism, and lipid peroxidation. Additionally, untargeted metabolomics was performed to identify metabolic pathways influenced by FIN. Key Results: FIN improved renal function and alleviated renal injury and fibrosis in both diabetic mouse models. It inhibited MR overactivation, regulated iron metabolism, reduced iron overload, and suppressed lipid peroxidation. Moreover, FIN upregulated ferroptosis-related proteins GPX4 and SLC7A11. Metabolomics analysis revealed that FIN modulated ferroptosis-related metabolic pathways, including antioxidant defense and lipid peroxidation. Conclusion and Implications: FIN protects against DKD by targeting ferroptosis through MR inhibition, iron regulation, and lipid peroxidation reduction. These findings provide new insights into the therapeutic mechanisms of FIN in DKD, suggesting its potential as a therapeutic agent for DKD and other ferroptosis-related renal disorders. However, further studies are needed to validate these findings in clinical settings. Supplementary Material File (figure-1.tif) Download 9.93 MB File (figure-2.tif) Download 8.10 MB File (figure-3.tif) Download 9.87 MB File (figure-4.tif) Download 9.15 MB File (figure-5.tif) Download 9.91 MB File (figure-6.tif) Download 9.91 MB File (figure-7.tif) Download 1.61 MB File (main document.doc) Download 718.50 KB Information & Authors Information Version history V1 Version 1 28 October 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Mingyan Zhang Xiamen University School of Medicine View all articles by this author Shanpan Fu Xiamen University School of Medicine View all articles by this author Yuemei Xi Xiamen University School of Medicine View all articles by this author Qiang Wang Zhejiang Provincial People's Hospital Urology and Nephrology Center View all articles by this author De Xie Xiamen University School of Medicine View all articles by this author Junliang He Xiamen University School of Life Sciences View all articles by this author Linqian Yu Xiamen University School of Medicine View all articles by this author Qian Zhang Xiamen University School of Medicine View all articles by this author Jiayu Chen Xiamen University School of Medicine View all articles by this author Liushuang Xu Xiamen University School of Medicine View all articles by this author Yayan Liu Xiamen University School of Medicine View all articles by this author Xueling Ye Xiamen University School of Medicine View all articles by this author Mengni Wu Xiamen University School of Medicine View all articles by this author Wanling Que Xiamen University School of Medicine View all articles by this author Shuyi Chen Xiamen University School of Medicine View all articles by this author Shuai Huang Xiamen University School of Medicine View all articles by this author Cuiying Ye Xiamen University School of Medicine View all articles by this author Tetsuya Yamamoto Osaka Gyoumeikan Hospital View all articles by this author Hidenori Koyama Hyogo College of Medicine View all articles by this author jidong Cheng [email protected] Xiamen University School of Medicine View all articles by this author Yanhui Wu Xiamen University School of Medicine View all articles by this author Metrics & Citations Metrics Article Usage 158 views 96 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Mingyan Zhang, Shanpan Fu, Yuemei Xi, et al. Non-steroid Mineralocorticoid Receptor Antagonist Finerenone Improves Diabetic Kidney Disease Through Inhibiting Ferroptosis of Renal Tubule. Authorea . 28 October 2025. DOI: https://doi.org/10.22541/au.176165565.56119616/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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