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Accurate Estimation of Glomerular Filtration Rate in Critically Ill Infants and Children Using a Iohexol Population
Evelyn Dhont1,2, Alexandre Destere3,4, Alexandre Gerard3
1Pediatric Intensive Care Unit 1K12D, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium. evelyn.dhont@uzgent.be.
Insights
A new formula for estimating glomerular filtration rate (GFR) in critically ill children, eGFRiohexol, shows improved accuracy, especially for infants. This model-based approach offers a practical bedside tool for assessing kidney function, outperforming existing methods.
Area of Science:
- Pediatric Nephrology
- Pharmacokinetics
- Critical Care Medicine
Background:
- Accurate glomerular filtration rate (GFR) assessment is vital in critically ill children, but standard estimation formulas (eGFR) show poor performance, particularly in neonates and infants.
- Iohexol plasma clearance is the gold standard for measured GFR, but its clinical application is hindered by logistical challenges.
Purpose of the Study:
- To develop and validate a population pharmacokinetic model for iohexol in critically ill children.
- To derive a practical, model-based GFR estimation formula (eGFRiohexol).
- To compare the predictive performance of eGFRiohexol against established formulas like eGFRSchwartz and eGFRSmeets/Pierce.
Main Methods:
- A population pharmacokinetic model was built using iohexol plasma concentrations from 93 critically ill children, with validation in 31 patients.
- Reference GFR clearances were determined using post hoc Bayesian estimates.
- Predictive performance was evaluated using bias, imprecision, Total Deviation Index, concordance correlation coefficient, and percentage of predictions within 10% and 30% error (P10, P30).
Main Results:
- The final model identified body surface area, serum creatinine, cystatin C, postoperative status, and clonidine treatment as key predictors of iohexol clearance.
- eGFRiohexol demonstrated excellent performance with minimal bias (-0.8%), low imprecision (21%), and high accuracy (P30 = 87%).
- eGFRiohexol showed superior accuracy in children under 2 years (P30 = 90%) compared to eGFRSchwartz (P30 = 40%) and outperformed eGFRSmeets/Pierce (P30 = 68%).
Conclusions:
- A GFR estimation formula derived from iohexol population pharmacokinetic modeling offers accurate bedside assessment of kidney function in critically ill children.
- eGFRiohexol significantly outperforms the Schwartz and Smeets/Pierce formulas, especially in infants.
- Further external validation in diverse pediatric intensive care unit populations is recommended to confirm generalizability and clinical utility.
Background And Objective:
Accurate assessment of the glomerular filtration rate (GFR) is crucial in critically ill children, yet standard estimation formulas (eGFR) perform poorly, especially in the youngest. Iohexol plasma clearance is the reference standard for measured GFR; however, its routine use is limited by logistical constraints. This study aims to develop and internally validate a population pharmacokinetic model of iohexol in critically ill children, to derive a practical model-based GFR estimation formula (eGFRiohexol), and to compare its predictive performance against established eGFR formulas (eGFRSchwartz, eGFRSmeets/Pierce).
Methods:
After administration of iohexol, up to six blood samples were drawn from 107 patients over a 6-hour interval. Data from 93 patients were used for model building, and from 31 patients for internal validation. Reference clearances were obtained using the post hoc Bayesian clearance estimates. Predictive performances of eGFRiohexol, eGFRSchwartz, and eGFRSmeets/Pierce were compared with reference clearances using bias, imprecision, Total Deviation Index, concordance correlation coefficient, and the percentage of predictions within 10 and 30% error (P10, P30) around reference clearances.
Results:
The final model identified body surface area, serum creatinine, cystatin C, postoperative status, and clonidine treatment as significant predictors of iohexol clearance. eGFRiohexol demonstrated minimal bias (-0.8%) and imprecision (21%) and high accuracy (P30 = 87%), particularly in patients under 2 years of age (P30 = 90 vs 40% for eGFRSchwartz). Furthermore, eGFRiohexol also demonstrated superiority over eGFRSmeets/Pierce, which exhibited moderate bias (-5.4%) and reduced accuracy (P30 = 68%).
Conclusions:
A model-derived GFR estimation formula based on iohexol population pharmacokinetic modeling might allow for an accurate bedside assessment of kidney function in critically ill children, outperforming the Schwartz and Smeets/Pierce formulas, particularly in infants. External validation in larger pediatric intensive care unit populations, across the full age and GFR range, is warranted to confirm the generalizability of this equation and its potential for broader clinical application.
Clinical Trial Registration:
ClinicalTrials.gov NCT05179564, registered retrospectively on 5 January, 2022.
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