ArticlePloS one2015
Endocytotic uptake of zoledronic acid by tubular cells may explain its renal effects in cancer patients receiving high doses of the compound.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Fanconi Syndrome After a Single Exposure to Intravenous Zoledronic Acid.Clinical case reports · 2026Article
- Article
- Evaluate the renal system damage caused by zoledronic acid: a comprehensive analysis of adverse events from FAERS.BMC cancer · 2024Article
- The dynamin inhibitor, dynasore, prevents zoledronate-induced viability loss in human gingival fibroblasts by partially blocking zoledronate uptake and inhibiting endosomal acidification.Journal of applied oral science : revista FOB · 2024Article
- Zoledronic Acid-Associated Fanconi Syndrome in Patients With Cancer.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2022Article
- A Mathematical Model of In Vitro Cellular Uptake of Zoledronic Acid and Isopentenyl Pyrophosphate Accumulation.Pharmaceutics · 2022Article
- Article
- LongitudinalFrontiers in bioengineering and biotechnology · 2022Article
- Review
- Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity.Archives of toxicology · 2018Article
- Zoledronic acid induces apoptosis via stimulating the expressions of ERN1, TLR2, and IRF5 genes in glioma cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Fluorescent Bisphosphonate and Carboxyphosphonate Probes: A Versatile Imaging Toolkit for Applications in Bone Biology and Biomedicine.Bioconjugate chemistry · 2016Article
- Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin-Darby canine kidney cells.Toxicology reports · 2015Article
- Early onset acute tubular necrosis following single infusion of zoledronate.Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal DiseasesArticle
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zoledronic acid, a highly potent nitrogen-containing bisphosphonate used for the treatment of pathological bone loss, is excreted unmetabolized via the kidney if not bound to the bone. In cancer patients receiving high doses of the compound renal excretion may be associated with acute tubular necrosis. The question of how zoledronic acid is internalized by renal tubular cells has not been answered until now. In the current work, using a primary human tubular cell culture system, the pathway of cellular uptake of zoledronic acid (fluorescently/radiolabeled) and its cytotoxicity were investigated. Previous studies in our laboratory have shown that this primary cell culture model consistently mimics the physiological characteristics of molecular uptake/transport of the epithelium in vivo. Zoledronic acid was found to be taken up by tubular cells via fluid-phase-endocytosis (from apical and basolateral side) as evidenced by its co-localization with dextran. Cellular uptake and the resulting intracellular level was twice as high from the apical side compared to the basolateral side. Furthermore, the intracellular zoledronic acid level was found to be dependent on the administered concentration and not saturable. Cytotoxic effects however, were only seen at higher administration doses and/or after longer incubation times. Although zoledronic acid is taken up by tubular cells, no net tubular transport could be measured. It is concluded that fluid-phase-endocytosis of zoledronic acid and cellular accumulation at high doses may be responsible for the acute tubular necrosis observed in some cancer patients receiving high doses of the compound.
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