Determining the mechanisms underlying augmented renal drug clearance in the critically ill: use of exogenous marker compounds

Udy, Andrew A., Jarrett, Paul, Stuart, Janine, Lassig-Smith, Melissa, Starr, Therese, Dunlop, Rachel, Wallis, Steven C., Roberts, Jason A. and Lipman, Jeffrey (2014) Determining the mechanisms underlying augmented renal drug clearance in the critically ill: use of exogenous marker compounds. Critical Care, 18 657: 1-9. doi:10.1186/s13054-014-0657-z

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Author Udy, Andrew A.
Jarrett, Paul
Stuart, Janine
Lassig-Smith, Melissa
Starr, Therese
Dunlop, Rachel
Wallis, Steven C.
Roberts, Jason A.
Lipman, Jeffrey
Title Determining the mechanisms underlying augmented renal drug clearance in the critically ill: use of exogenous marker compounds
Journal name Critical Care   Check publisher's open access policy
ISSN 1466-609X
Publication date 2014-11-29
Year available 2014
Sub-type Article (original research)
DOI 10.1186/s13054-014-0657-z
Open Access Status DOI
Volume 18
Issue 657
Start page 1
End page 9
Total pages 9
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2015
Language eng
Formatted abstract

The 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.


This 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.


Twenty 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.


In 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
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