Observational studyCritical care (London, England)2014
Determining the mechanisms underlying augmented renal drug clearance in the critically ill: use of exogenous marker compounds.
Observational study in Critical care (London, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06266494 (Prevention and Treatment of Frostbite Infection With Antimicrobial Pharmacokinetic Analysis), which is not on this map. Cited by 32 papers, 2 of them syntheses that pooled it.
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.
Prevention and Treatment of Frostbite Infection With Antimicrobial Pharmacokinetic Analysis
Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 83 citations in OpenAlex.
- The intact nephron hypothesis as a model for renal drug handling.European journal of clinical pharmacology · 2019Pooled it
- Augmented Renal Clearance in Critically Ill Patients: A Systematic Review.Clinical pharmacokinetics · 2018Pooled it
- The long walk to a short half-life: the discovery of augmented renal clearance and its impact on antibiotic dosing.The Journal of antimicrobial chemotherapy · 2025Review
- The Impact of Augmented Renal Clearance on the Pharmacokinetics of Levetiracetam in Critically Ill Patients: A Literature Review.Journal of clinical pharmacology · 2025Review
- Augmented Renal Clearance: Prevalence, Risk Factors and Underlying Mechanism in Critically Ill Patients with Subarachnoid Hemorrhage.Neurocritical care · 2025Article
- Pharmacotherapy variability and precision medicine in neurocritical care.Frontiers in neurology · 2025Review
- Enhanced renal clearance impacts levetiracetam concentrations in patients with traumatic brain injury with and without augmented renal clearance.BMC neurology · 2024Article
- Personalized application of antimicrobial drugs in pediatric patients with augmented renal clearance: a review of literature.European journal of pediatrics · 2024Review
- Pharmacokinetic relevance of glomerular hyperfiltration for drug dosing.Clinical kidney journal · 2023Review
- The Significance of Bayesian Pharmacokinetics in Dosing for Critically Ill Patients: A Primer for Clinicians Using Vancomycin as an Example.Antibiotics (Basel, Switzerland) · 2023Review
- Prevalence and prediction of augmented renal clearance in the neurocritical care population.Journal of neurocritical care · 2022Article
- Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance.The Journal of antimicrobial chemotherapy · 2022Article
- Development of a decision flowchart to identify the patients need high-dose vancomycin in early phase of treatment.Journal of pharmaceutical health care and sciences · 2022Article
- Augmented renal clearance in critically ill COVID-19 patients: Forewarned is forearmed.Journal of critical care · 2021Article
- Augmented Renal Clearance, Muscle Catabolism and Urinary Nitrogen Loss: Implications for Nutritional Support in Critically Ill Trauma Patients.Nutrients · 2021Article
- Population Pharmacokinetics and Dosing Optimization of Vancomycin in Infants, Children, and Adolescents with Augmented Renal Clearance.Antimicrobial agents and chemotherapy · 2021Article
- Augmented renal clearance in critically ill patients with cancer (ARCCAN Study): A prospective observational study evaluating prevalence and risk factors.Pharmacology research & perspectives · 2021Observational
- Optimizing Aminoglycoside Dosing Regimens for Critically Ill Pediatric Patients with Augmented Renal Clearance: a Convergence of Parametric and Nonparametric Population Approaches.Antimicrobial agents and chemotherapy · 2021Article
- Ensuring Sufficient Trough Plasma Concentrations for Broad-Spectrum Beta-Lactam Antibiotics in Children With Malignancies: Beware of Augmented Renal Clearance!Frontiers in pediatrics · 2021Article
- Population Pharmacokinetics Modeling of Vancomycin Among Chinese Infants With Normal and Augmented Renal Function.Frontiers in pediatrics · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe aim of this study was to explore changes in glomerular filtration (GFR) and renal tubular function in critically ill patients at risk of augmented renal clearance (ARC), using exogenous marker compounds.
methodsThis prospective, observational pharmacokinetic (PK) study was performed in a university-affiliated, tertiary-level, adult intensive care unit (ICU). Patients aged less than or equal to 60 years, manifesting a systemic inflammatory response, with an expected ICU length of stay more than 24 hours, no evidence of acute renal impairment (plasma creatinine concentration < 120 μmol/L) and no history of chronic kidney disease or renal replacement therapy were eligible for inclusion. The following study markers were administered concurrently: sinistrin 2,500 mg (Inutest; Laevosan, Linz, Austria), p-aminohippuric acid (PAH) 440 mg (4% p-aminohippuric acid sodium salt; CFM Oskar Tropitzsch, Marktredwitz, Germany), rac-pindolol 5 or 15 mg (Barbloc; Alphapharm, Millers Point, NSW, Australia) and fluconazole 100 mg (Diflucan; Pfizer Australia Pty Ltd, West Ryde, NSW, Australia). Plasma concentrations were then measured at 5, 10, 15, 30, 60 and 120 minutes and 4, 6, 12 and 24 hours post-administration. Non-compartmental PK analysis was used to quantify GFR, tubular secretion and tubular reabsorption.
resultsTwenty patients were included in the study. Marker administration was well tolerated, with no adverse events reported. Sinistrin clearance as a marker of GFR was significantly elevated (mean, 180 (95% confidence interval (CI), 141 to 219) ml/min) and correlated well with creatinine clearance (r = 0.70, P < 0.01). Net tubular secretion of PAH, a marker of tubular anion secretion, was also elevated (mean, 428 (95% CI, 306 to 550) ml/min), as was net tubular reabsorption of fluconazole (mean, 135 (95% CI, 100 to 169) ml/min). Net tubular secretion of (S)- and (R)-pinodolol, a marker of tubular cation secretion, was impaired.
conclusionsIn critically ill patients at risk of ARC, significant alterations in glomerular filtration, renal tubular secretion and tubular reabsorption are apparent. This has implications for accurate dosing of renally eliminated drugs.
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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.