ArticleRenal failure2025
Dapagliflozin improves diabetic kidney disease by inhibiting ferroptosis through β-hydroxybutyrate production.
Article in Renal failure, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Navigating the nexus: synergistic challenges in diabetes, hypertension, and renal medicine.Renal failure · 2026Article
- Overexpression of LINC00472 alleviates diabetic kidney disease progression via the miR-21-5p/STAT3 axis.Renal failure · 2026Article
- SPARC Drives Podocyte Mitochondrial Damage and Ferroptosis in Diabetic Kidney Disease Following Klotho Deficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From molecules to the clinic-pathophysiology of sodium-glucose cotransporter 2 inhibitors and their emerging role in urology: A comprehensive review from the European Association of Urology Section of Endourology.Asian journal of urology · 2026Review
- Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Advances in targeted treatment of ferroptosis in diabetic kidney disease with SGLT2 inhibitors.Diabetology & metabolic syndrome · 2026Review
- [Different Astragalus medicinal pairs improve diabetic nephropathy in mice by regulating lipid peroxidation through PTGS2].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Tubular injury in diabetic kidney disease: a focus on regulated cell death.Frontiers in endocrinology · 2026Review
- Recalibrating cell fate: targeting the mitochondrial signaling hub with natural active compounds to inhibit regulated cell death in diabetic kidney disease.Frontiers in physiology · 2026Review
- Role of Treg cells in diabetes mellitus and association with traditional Chinese medicine: a literature review.Frontiers in immunology · 2026Review
- Ferroptosis regulation by SGLT2 inhibitors: mechanisms and clinical benefits in diabetic kidney disease.Frontiers in pharmacology · 2026Review
- New Horizons in Metabolic Health: Unveiling the Future of Drug Discovery and Development.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Qing-Re-Xiao-Zheng-yi-qi formula protects renal function by stabilizing lysosomal membranes and inhibiting NLRP3-inflammasome-mediated pyroptosis in diabetic kidney disease.Annals of medicine · 2025Article
- Pathogenesis and Therapeutic Perspectives of Tubular Injury in Diabetic Kidney Disease: An Update.Biomedicines · 2025Review
- Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular-Kidney-Metabolic (CKM) Syndrome.Antioxidants (Basel, Switzerland) · 2025Review
- Qianshi Mixture Treats Diabetic Nephropathy by Regulating Lipid Metabolism Reprogramming and Inhibiting Oxidative Stress Damage.Journal of cellular and molecular medicine · 2025Article
- Programmed Cell Death in Diabetic Kidney Disease: Mechanisms and Therapeutic Targeting.Journal of inflammation research · 2025Review
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7 authors.
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Abstract
backgroundDiabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2i) are antihyperglycemic agents that provide additional renal-protective effects in patients with DKD, independent of their glucose-lowering effects. However, the underlying mechanism remains unclear. This study hypothesized that SGLT2i could alleviate diabetic kidney injury by inhibiting ferroptosis and explored its potential mechanisms.
methodsC57BL/6J mice were randomly divided into the control, DKD, DKD+dapagliflozin, and DKD+insulin treatment groups. Blood glucose levels and body weight were monitored. Renal function, tissue pathology, mitochondrial morphology and function, and lipid peroxidation biomarkers (lipid peroxidation [LPO], malondialdehyde [MDA], glutathione peroxidase 4 [GPX4], glutathione [GSH], and cystine transporter solute carrier family 7 member 11 [SLC7A11]) were evaluated. Human proximal tubule cells (HK2 cells) were exposed to high glucose alone or in combination with dapagliflozin. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) level, NAD+/NADH ratio (oxidized/reduced ratio of nicotinamide adenine dinucleotide), and lipid peroxidation were measured. In addition, the role of the β-hydroxybutyrate- Calcium/Calmodulin Dependent Protein Kinase Kinase 2 (BHB-CaMKK2) axis in mediating dapagliflozin regulating ferroptosis was examined.
resultsDapagliflozin significantly ameliorated kidney injury in mice with DKD. Typical changes in ferroptosis, including lipid peroxidation and impaired antioxidant capacity, increased in mice with DKD and HG-treated HK-2 cells. Dapagliflozin significantly improves ferroptosis-related lipid peroxidation and mitochondrial dysfunction. Furthermore, dapagliflozin suppressed the expression of CaMKK2, a key ferroptosis regulator. Specific CaMKK2 inhibitors alleviated mitochondrial damage and ferroptosis, whereas a CaMKK2 agonist counteracted the protective effects of dapagliflozin against mitochondrial, antioxidant, and anti-ferroptosis effects. In addition, dapagliflozin increased BHB production, which mediates its nephroprotective effects.
conclusionDapagliflozin improves DKD by inhibiting ferroptosis, promoting BHB production, and regulating CaMKK2.
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