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Predictors of augmented renal clearance based on iohexol plasma clearance in critically ill children

Evelyn Dhont (UGent) , Tatjana Van Der Heggen, Evelien Snauwaert (UGent) , Jef Willems (UGent) , Siska Croubels (UGent) , Joris Delanghe (UGent) , Jan De Waele (UGent) , Roos Colman (UGent) , Johan Vande Walle (UGent) , Peter De Paepe (UGent) , et al.
(2024) PEDIATRIC NEPHROLOGY. 39. p.1607-1616
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Abstract
BackgroundAugmented renal clearance (ARC) holds a risk of subtherapeutic drug concentrations. Knowledge of patient-, disease-, and therapy-related factors associated with ARC would allow predicting which patients would benefit from intensified dosing regimens. This study aimed to identify ARC predictors and to describe ARC time-course in critically ill children, using iohexol plasma clearance (CLiohexol) to measure glomerular filtration rate (GFR).MethodsThis is a retrospective analysis of data from the "IOHEXOL" study which validated GFR estimating formulas (eGFR) against CLiohexol. Critically ill children with normal serum creatinine were included, and CLiohexol was performed as soon as possible after pediatric intensive care unit (PICU) admission (CLiohexol1) and repeated (CLiohexol2) after 48-72 h whenever possible. ARC was defined as CLiohexol exceeding normal GFR for age plus two standard deviations.ResultsEighty-five patients were included; 57% were postoperative patients. Median CLiohexol1 was 122 mL/min/1.73 m2 (IQR 75-152). Forty patients (47%) expressed ARC on CLiohexol1. Major surgery other than cardiac surgery and eGFR were found as independent predictors of ARC. An eGFR cut-off value of 99 mL/min/1.73 m2 and 140 mL/min/1.73 m2 was suggested to identify ARC in children under and above 2 years, respectively. ARC showed a tendency to persist on CLiohexol2.ConclusionsOur findings raise PICU clinician awareness about increased risk for ARC after major surgery and in patients with eGFR above age-specific thresholds. This knowledge enables identification of patients with an ARC risk profile who would potentially benefit from a dose increase at initiation of treatment to avoid underexposure.Trial registrationClinicalTrials.gov NCT05179564, registered retrospectively on January 5, 2022.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information
Keywords
Augmented renal clearance, Glomerular filtration rate, idney function, Intensive care, Children

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MLA
Dhont, Evelyn, et al. “Predictors of Augmented Renal Clearance Based on Iohexol Plasma Clearance in Critically Ill Children.” PEDIATRIC NEPHROLOGY, vol. 39, 2024, pp. 1607–16, doi:10.1007/s00467-023-06221-4.
APA
Dhont, E., Van Der Heggen, T., Snauwaert, E., Willems, J., Croubels, S., Delanghe, J., … De Cock, P. (2024). Predictors of augmented renal clearance based on iohexol plasma clearance in critically ill children. PEDIATRIC NEPHROLOGY, 39, 1607–1616. https://doi.org/10.1007/s00467-023-06221-4
Chicago author-date
Dhont, Evelyn, Tatjana Van Der Heggen, Evelien Snauwaert, Jef Willems, Siska Croubels, Joris Delanghe, Jan De Waele, et al. 2024. “Predictors of Augmented Renal Clearance Based on Iohexol Plasma Clearance in Critically Ill Children.” PEDIATRIC NEPHROLOGY 39: 1607–16. https://doi.org/10.1007/s00467-023-06221-4.
Chicago author-date (all authors)
Dhont, Evelyn, Tatjana Van Der Heggen, Evelien Snauwaert, Jef Willems, Siska Croubels, Joris Delanghe, Jan De Waele, Roos Colman, Johan Vande Walle, Peter De Paepe, and Pieter De Cock. 2024. “Predictors of Augmented Renal Clearance Based on Iohexol Plasma Clearance in Critically Ill Children.” PEDIATRIC NEPHROLOGY 39: 1607–1616. doi:10.1007/s00467-023-06221-4.
Vancouver
1.
Dhont E, Van Der Heggen T, Snauwaert E, Willems J, Croubels S, Delanghe J, et al. Predictors of augmented renal clearance based on iohexol plasma clearance in critically ill children. PEDIATRIC NEPHROLOGY. 2024;39:1607–16.
IEEE
[1]
E. Dhont et al., “Predictors of augmented renal clearance based on iohexol plasma clearance in critically ill children,” PEDIATRIC NEPHROLOGY, vol. 39, pp. 1607–1616, 2024.
@article{01HQTMVTWRP8ETTHAG5MWRFB0W,
  abstract     = {{BackgroundAugmented renal clearance (ARC) holds a risk of subtherapeutic drug concentrations. Knowledge of patient-, disease-, and therapy-related factors associated with ARC would allow predicting which patients would benefit from intensified dosing regimens. This study aimed to identify ARC predictors and to describe ARC time-course in critically ill children, using iohexol plasma clearance (CLiohexol) to measure glomerular filtration rate (GFR).MethodsThis is a retrospective analysis of data from the "IOHEXOL" study which validated GFR estimating formulas (eGFR) against CLiohexol. Critically ill children with normal serum creatinine were included, and CLiohexol was performed as soon as possible after pediatric intensive care unit (PICU) admission (CLiohexol1) and repeated (CLiohexol2) after 48-72 h whenever possible. ARC was defined as CLiohexol exceeding normal GFR for age plus two standard deviations.ResultsEighty-five patients were included; 57% were postoperative patients. Median CLiohexol1 was 122 mL/min/1.73 m2 (IQR 75-152). Forty patients (47%) expressed ARC on CLiohexol1. Major surgery other than cardiac surgery and eGFR were found as independent predictors of ARC. An eGFR cut-off value of 99 mL/min/1.73 m2 and 140 mL/min/1.73 m2 was suggested to identify ARC in children under and above 2 years, respectively. ARC showed a tendency to persist on CLiohexol2.ConclusionsOur findings raise PICU clinician awareness about increased risk for ARC after major surgery and in patients with eGFR above age-specific thresholds. This knowledge enables identification of patients with an ARC risk profile who would potentially benefit from a dose increase at initiation of treatment to avoid underexposure.Trial registrationClinicalTrials.gov NCT05179564, registered retrospectively on January 5, 2022.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information}},
  author       = {{Dhont, Evelyn and Van Der Heggen, Tatjana and Snauwaert, Evelien and Willems, Jef and Croubels, Siska and Delanghe, Joris and De Waele, Jan and Colman, Roos and Vande Walle, Johan and De Paepe, Peter and De Cock, Pieter}},
  issn         = {{0931-041X}},
  journal      = {{PEDIATRIC NEPHROLOGY}},
  keywords     = {{Augmented renal clearance,Glomerular filtration rate,idney function,Intensive care,Children}},
  language     = {{eng}},
  pages        = {{1607--1616}},
  title        = {{Predictors of augmented renal clearance based on iohexol plasma clearance in critically ill children}},
  url          = {{http://doi.org/10.1007/s00467-023-06221-4}},
  volume       = {{39}},
  year         = {{2024}},
}

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