ArticleArchives of toxicology2018
Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity.
Article in Archives of toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 40 citations in OpenAlex.
- Analysis of the tumor reactivity of autologous TILs and allogeneic γδ T cells via tumor organoid-immune cell coculture.Journal of translational medicine · 2026Article
- Dynamic Changes in Serum Biochemical Indices and Alternative Splicing Events Revealed Molecular Regulatory Mechanisms in Rainbow Trout Under Copper Stress.Marine biotechnology (New York, N.Y.) · 2026Article
- Tubular ACSM3 deficiency impairs medium-chain fatty acid metabolism and aggravates kidney fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Evaluate the renal system damage caused by zoledronic acid: a comprehensive analysis of adverse events from FAERS.BMC cancer · 2024Article
- Article
- Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease.Nature reviews. Nephrology · 2023Review
- PI3K/AKT/mTOR Dysregulation and Reprogramming Metabolic Pathways in Renal Cancer: Crosstalk with the VHL/HIF Axis.International journal of molecular sciences · 2023Review
- Review
- Review
- Zoledronic Acid-Associated Fanconi Syndrome in Patients With Cancer.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2022Article
- Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis.Cell death & disease · 2020Article
- Fatty acid transport protein-2 regulates glycemic control and diabetic kidney disease progression.JCI insight · 2020Article
- A Non-Targeted Capillary Electrophoresis-Mass Spectrometry Strategy to Study Metabolic Differences in an In vitro Model of High-Glucose Induced Changes in Human Proximal Tubular HK-2 Cells.Molecules (Basel, Switzerland) · 2020Article
- Tussilagone Inhibits Osteoclastogenesis and Periprosthetic Osteolysis by Suppressing the NF-κB and P38 MAPK Signaling Pathways.Frontiers in pharmacology · 2020Article
- Recent Progress on Lipid Intake and Chronic Kidney Disease.BioMed research international · 2020Review
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
Zoledronate is a bisphosphonate that is widely used in the treatment of metabolic bone diseases. However, zoledronate induces significant nephrotoxicity associated with acute tubular necrosis and renal fibrosis when administered intravenously. There is speculation that zoledronate-induced nephrotoxicity may result from its pharmacological activity as an inhibitor of the mevalonate pathway but the molecular mechanisms are not fully understood. In this report, human proximal tubular HK-2 cells and mouse models were combined to dissect the molecular pathways underlying nephropathy caused by zoledronate treatments. Metabolomic and proteomic assays revealed that multiple cellular processes were significantly disrupted, including the TGFβ pathway, fatty acid metabolism and small GTPase signaling in zoledronate-treated HK-2 cells (50 μM) as compared with those in controls. Zoledronate treatments in cells (50 μM) and mice (3 mg/kg) increased TGFβ/Smad3 pathway activation to induce fibrosis and kidney injury, and specifically elevated lipid accumulation and expression of fibrotic proteins. Conversely, fatty acid transport protein Slc27a2 deficiency or co-administration of PPARA agonist fenofibrate (20 mg/kg) prevented zoledronate-induced lipid accumulation and kidney fibrosis in mice, indicating that over-expression of fatty acid transporter SLC27A2 and defective fatty acid β-oxidation following zoledronate treatments were significant factors contributing to its nephrotoxicity. These pharmacological and genetic studies provide an important mechanistic insight into zoledronate-associated kidney toxicity that will aid in development of therapeutic prevention and treatment options for this nephropathy.
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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.