ArticleThe Journal of antimicrobial chemotherapy2019
Twenty-four hour pharmacokinetic relationships for intravenous vancomycin and novel urinary biomarkers of acute kidney injury in a rat model.
Article in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- The monitoring of vancomycin: a systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing.BMC infectious diseases · 2021Pooled it
- Big Data Bayesian Truths: No Vancomycin Trough Concentration Target Is Sufficiently Precise for Safety or Efficacy.Open forum infectious diseases · 2025Trial
- Risk Factors for Nephrotoxicity in Methicillin-Resistant Staphylococcus aureus Bacteraemia: A Post Hoc Analysis of the CAMERA2 Trial.Clinical drug investigation · 2023Trial
- Optimizing vancomycin therapy: the critical role of dosing frequency, AUC monitoring and gender: a retrospective cohort study.Frontiers in pharmacology · 2026Article
- A Large Cohort Study to Identify Risk Factors of Acute Kidney Injury in Pediatric Patients Undergoing Intravenous Vancomycin Therapy.Pharmacotherapy · 2025Article
- Protamine protects against vancomycin-induced kidney injury.Antimicrobial agents and chemotherapy · 2025Article
- Past, present, and future biomarkers of kidney function and injury: The relationship with antibiotics.International journal of antimicrobial agents · 2024Review
- Relationship between nephrotoxicity and area under the concentration-time curve of vancomycin in critically ill patients: a multicenter retrospective study.Microbiology spectrum · 2024Observational
- Impact of humanized vancomycin infusion on kidney function and kidney injury in a translational rat model.International journal of antimicrobial agents · 2024Article
- Flucloxacillin worsens while imipenem-cilastatin protects against vancomycin-induced kidney injury in a translational rat model.British journal of pharmacology · 2024Article
- Iohexol-Measured Glomerular Filtration Rate and Urinary Biomarker Changes between Vancomycin and Vancomycin Plus Piperacillin-Tazobactam in a Translational Rat Model.Antimicrobial agents and chemotherapy · 2023Article
- Iohexol-measured glomerular filtration rate and urinary biomarker changes between vancomycin and vancomycin plus piperacillin-tazobactam in a translational rat model.bioRxiv : the preprint server for biology · 2023Article
- Impact of Vancomycin Loading Doses and Dose Escalation on Glomerular Function and Kidney Injury Biomarkers in a Translational Rat Model.Antimicrobial agents and chemotherapy · 2023Article
- Blood Biomarkers and Metabolomic Profiling for the Early Diagnosis of Vancomycin-Associated Acute Kidney Injury: A Systematic Review and Meta-Analysis of Experimental Studies.Journal of personalized medicine · 2022Review
- Piperacillin-Tazobactam Plus Vancomycin-Associated Acute Kidney Injury in Adults: Can Teicoplanin or Other Antipseudomonal Beta-Lactams Be Remedies?Healthcare (Basel, Switzerland) · 2022Review
- Intra-articular versus systemic vancomycin for the treatment of periprosthetic joint infection after debridement and spacer implantation in a rat model.Bone & joint research · 2022Article
- Vancomycin-arginine (STM-001) abrogates ESBL carrier and carbapenem-resistant Escherichia coli burden in a murine complicated urinary tract infection model.The Journal of antimicrobial chemotherapy · 2022Article
- Vancomycin Pharmacokinetics in a Pregnancy Rat Model.Antimicrobial agents and chemotherapy · 2022Article
- A translational rat model to assess glomerular function changes with vancomycin.International journal of antimicrobial agents · 2022Article
- Glomerular Function and Urinary Biomarker Changes between Vancomycin and Vancomycin plus Piperacillin-Tazobactam in a Translational Rat Model.Antimicrobial agents and chemotherapy · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesTo identify the pharmacokinetic (PK) and toxicodynamic (TD) relationship for vancomycin-induced kidney injury.
methodsMale Sprague-Dawley rats received intravenous (iv) vancomycin. Doses ranging from 150 mg/kg/day to 400 mg/kg/day were administered as a single or twice-daily injection over 24 h (total protocol duration). Controls received iv saline. Plasma was sampled with up to eight samples in 24 h per rat. Twenty-four hour urine was collected and assayed for kidney injury molecule 1 (KIM-1), osteopontin and clusterin. Vancomycin in plasma was quantified via LC-MS/MS. PK analyses were conducted using Pmetrics for R. PK exposures during the first 24 h (i.e. AUC0-24h, Cmax 0-24h and Cmin 0-24h) were calculated. PK/TD relationships were assessed with Spearman's rank coefficient (rs) and the best-fit mathematical model.
resultsPK/TD data were generated from 45 vancomycin-treated and 5 control rats. A two-compartment model fit the data well (Bayesian: observed versus predicted R2 = 0.97). Exposure-response relationships were found between AUC0-24h versus KIM-1 and osteopontin (R2 = 0.61 and 0.66) and Cmax 0-24h versus KIM-1 and osteopontin (R2 = 0.50 and 0.56) using a four-parameter Hill fit. Conversely, Cmin 0-24h was less predictive of KIM-1 and osteopontin (R2 = 0.46 and 0.53). A vancomycin AUC0-24h of 482.2 corresponded to a 90% of maximal rise in KIM-1.
conclusionsVancomycin-induced kidney injury as defined by urinary biomarkers is driven by vancomycin AUC or Cmax rather than Cmin. Further, an identified PK/TD target AUC0-24h of 482.2 mg·h/L may have direct relevance to human outcomes.
Indexed as
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.