ArticleAntimicrobial agents and chemotherapy2013
Megalin contributes to kidney accumulation and nephrotoxicity of colistin.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 109 citations in OpenAlex.
- Preliminary clinical study of the effect of ascorbic acid on colistin-associated nephrotoxicity.Antimicrobial agents and chemotherapy · 2015Trial
- Megalin: from structure to function.Nature reviews. Nephrology · 2026Review
- Antimicrobial-induced hyponatremia: pathophysiological mechanisms, implicated agents, and clinical management strategies.European journal of clinical pharmacology · 2026Review
- Preheating colistimethate sodium enhances its efficacy against multi/extensively drug-resistant Gram-negative bacilli in preservation fluid.Scientific reports · 2026Article
- Breaking the outer membrane barrier: structure, targets, and antimicrobial strategies for Gram-negative bacteria.Frontiers in microbiology · 2026Review
- Molecular mechanisms attributed to colistin renal proximal tubular epithelial cytotoxicity.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Review
- Population Pharmacokinetic/Toxicodynamic Model for Polymyxin B in Critically Ill Patients to Identify the Risk of Nephrotoxicity.Clinical pharmacology and therapeutics · 2025Observational
- L-carnitine co-administration prevents colistin-induced mitochondrial permeability transition and reduces the risk of acute kidney injury in mice.Scientific reports · 2024Article
- Mechanisms of gelofusine protection in an in vitro model of polymyxin B-associated renal injury.American journal of physiology. Renal physiology · 2024Article
- Comparison of the Impact of VRP-034 and Polymyxin B upon Markers of Kidney Injury in Human Proximal Tubule Monolayers In Vitro.Antibiotics (Basel, Switzerland) · 2024Article
- Dextrin conjugation to colistin inhibits its toxicity, cellular uptake and acute kidney injuryRSC pharmaceutics · 2024Article
- Recent Advances in the Development of Polymyxin Antibiotics: 2010-2023.ACS infectious diseases · 2024Review
- Tobramycin Reduces Pulmonary Toxicity of Polymyxin B via Inhibiting the Megalin-Mediated Drug Uptake in the Human Lung Epithelial Cells.Pharmaceutics · 2024Article
- Flucloxacillin worsens while imipenem-cilastatin protects against vancomycin-induced kidney injury in a translational rat model.British journal of pharmacology · 2024Article
- Genetic predisposition and high exposure to colistin in the early treatment period as independent risk factors for colistin-induced nephrotoxicity.Clinical and translational science · 2024Article
- Interactions Between Antimicrobial Peptides and Targets Responsible for their Nephrotoxic Action: Molecular Dynamics Simulations.Current drug safety · 2024Article
- In vivo evaluation of nephrotoxicity and neurotoxicity of colistin formulated with sodium deoxycholate sulfate in a mice model.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Overview of Antibiotic-Induced Nephrotoxicity.Kidney international reports · 2023Review
- Synchrotron-based X-ray fluorescence microscopy reveals accumulation of polymyxins in single human alveolar epithelial cells.Antimicrobial agents and chemotherapy · 2023Article
- Adverse Events and Drug Resistance in Critically Ill Patients Treated with Colistimethate Sodium: A Review of the Literature.Infection and drug resistance · 2023Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interest has recently been shown again in colistin because of the increased prevalence of infections caused by multidrug-resistant Gram-negative bacteria. Although the potential for nephrotoxicity is a major dose-limiting factor in colistin use, little is known about the mechanisms that underlie colistin-induced nephrotoxicity. In this study, we focused on an endocytosis receptor, megalin, that is expressed in renal proximal tubules, with the aim of clarifying the role of megalin in the kidney accumulation and nephrotoxicity of colistin. We examined the binding of colistin to megalin by using a vesicle assay. The kidney accumulation, urinary excretion, and concentrations in plasma of colistin in megalin-shedding rats were also evaluated. Furthermore, we examined the effect of megalin ligands and a microtubule-depolymerizing agent on colistin-induced nephrotoxicity. We found that cytochrome c, a typical megalin ligand, inhibited the binding of colistin to megalin competitively. In megalin-shedding rats, renal proximal tubule colistin accumulation was decreased (13.5 ± 1.6 and 21.3 ± 2.6 μg in megalin-shedding and control rats, respectively). Coadministration of colistin and cytochrome c or albumin fragments resulted in a significant decrease in urinary N-acetyl-β-d-glucosaminidase (NAG) excretion, a marker of renal tubular damage (717.1 ± 183.9 mU/day for colistin alone, 500.8 ± 102.4 mU/day for cytochrome c with colistin, and 406.7 ± 156.7 mU/day for albumin fragments with colistin). Moreover, coadministration of colistin and colchicine, a microtubule-depolymerizing agent, resulted in a significant decrease in urinary NAG excretion. In conclusion, our results indicate that colistin acts as a megalin ligand and that megalin plays a key role in the accumulation in the kidney and nephrotoxicity of colistin. Megalin ligands may be new targets for the prevention of colistin-induced nephrotoxicity.
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