ArticleCell discovery2023
Metformin potentiates nephrotoxicity by promoting NETosis in response to renal ferroptosis.
Article in Cell discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 56 citations in OpenAlex.
- Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026Review
- Dose-Dependent Association of Long-Term Metformin Use and Diabetic Nephropathy Risk in Patients with Type 2 Diabetes Mellitus: A Nationwide Population-Based Study in Taiwan.Clinical drug investigation · 2026Article
- Ferroptosis in T cells: mechanisms, biology and translational opportunities.Nature reviews. Immunology · 2026Review
- Regulated Cell Death in Fungi, the Role of Metacaspases and Assay Techniques.Methods and protocols · 2026Review
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Burden of chronic kidney disease caused by dietary risks in China from 1990 to 2021: a systematic analysis and comparison with global levels.Journal of clinical biochemistry and nutrition · 2026Article
- Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury.Biomolecules · 2026Review
- A Novel Protective Strategy Against Metformin-Induced Renal Injury Involving Adenosine Triphosphate and Thiamine Pyrophosphate.International journal of molecular sciences · 2026Article
- Hyperandrogenemia Induces Trophoblast Ferroptosis and Early Pregnancy Loss in Patients With PCOS via CMA-Dependent FTH1 Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neutrophil Extracellular Traps in Diabetic Kidney Disease: Mechanisms of Pathogenesis and Emerging Therapeutic Strategies.Drug design, development and therapy · 2026Review
- Adverse event reporting signals for SGLT-2 inhibitor-metformin combination therapy: a disproportionality analysis of the FAERS database.Frontiers in endocrinology · 2026Article
- The Current Application Prospects of Nanomedicine in Renal Ischemia-Reperfusion Injury.International journal of nanomedicine · 2026Review
- Ferroptosis: a promising therapeutic target for periodontitis.Frontiers in immunology · 2026Review
- FMRP regulation of STAT3-MYC signaling is critical for adult hippocampal neurogenesis and cognitive flexibility.Cell death and differentiation · 2026Article
- Mechanistic insights of hypoglycemic components fromFrontiers in endocrinology · 2026Article
- Glycyrrhizin alleviates contrast-induced acute kidney injury via inhibiting HMGB1-mediated renal tubular epithelial cells ferroptosis.Renal failure · 2025Article
- Associations of hypoglycemic medications, cordycepin and vaccination with clinical outcomes in diabetic kidney disease patients with COVID-19.Renal failure · 2025Article
- SLC39A8-mediated zinc dyshomeostasis potentiates kidney disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Study of Skeletal Stem Cell Dynamics and Its Potential Applications in the Design of a Titanium Implant for Senile Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NETosis-based prognostic model reveals immune modulation in clear cell renal cell carcinoma using single-cell and bulk RNA sequencing.Scientific reports · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Given the rapidly aging population, aging-related diseases are becoming an excessive burden on the global healthcare system. Metformin has been shown to be beneficial to many age-related disorders, as well as increase lifespan in preclinical animal models. During the aging process, kidney function progressively declines. Currently, whether and how metformin protects the kidney remains unclear. In this study, among longevity drugs, including metformin, nicotinamide, resveratrol, rapamycin, and senolytics, we unexpectedly found that metformin, even at low doses, exacerbated experimentally-induced acute kidney injury (AKI) and increased mortality in mice. By single-cell transcriptomics analysis, we found that death of renal parenchymal cells together with an expansion of neutrophils occurs upon metformin treatment after AKI. We identified programmed cell death by ferroptosis in renal parenchymal cells and blocking ferroptosis, or depleting neutrophils protects against metformin-induced nephrotoxicity. Mechanistically, upon induction of AKI, ferroptosis in renal parenchymal cells initiates the migration of neutrophils to the site of injury via the surface receptor CXCR4-bound to metformin-iron-NGAL complex, which results in NETosis aggravated AKI. Finally, we demonstrated that reducing iron showed protective effects on kidney injury, which supports the notion that iron plays an important role in metformin-triggered AKI. Taken together, these findings delineate a novel mechanism underlying metformin-aggravated nephropathy and highlight the mechanistic relationship between iron, ferroptosis, and NETosis in the resulting AKI.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.