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Optimal sampling strategies to assess inulin clearance in children by the inulin single-injection method
Lyonne K van Rossum1, Ron A A Mathot, Karlien Cransberg
1Department of Hospital Pharmacy, Erasmus MC, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. l.vanrossum@erasmusmc.nl
Insights
This study developed fewer blood sampling strategies for accurately measuring inulin clearance in children using the single-injection method. These optimized sampling times reduce patient burden without compromising reliable glomerular filtration rate estimation.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Pediatric Nephrology
- Clinical Chemistry
Background:
- Glomerular filtration rate (GFR) is crucial for assessing kidney function.
- The inulin single-injection method is a standard for GFR estimation but requires multiple blood samples.
- Minimizing blood draws is essential for pediatric patient comfort and practicality.
Purpose of the Study:
- To develop and validate reduced blood sampling strategies for inulin clearance measurement in pediatric patients.
- To enable accurate GFR prediction using fewer samples in the inulin single-bolus-injection method.
- To enhance the convenience and practicality of GFR assessment in children.
Main Methods:
- A population pharmacokinetic model was built using data from 100 pediatric patients.
- Optimal sampling times were identified using D-optimality theory.
- Bayesian estimates of inulin clearance were validated in 54 pediatric patients using 2-4 sampling times.
Main Results:
- Sampling strategies with 2-4 time points (including 240 min) accurately predicted inulin clearance (bias <3%, imprecision <15%).
- Even a single sample at 240 minutes showed acceptable performance.
- The validated strategies demonstrated high accuracy and reliability.
Conclusions:
- Reduced sampling strategies (2-4 samples, including one at 240 min) are effective for accurate inulin clearance prediction in children.
- These methods simplify the inulin clearance test for pediatric patients.
- The proposed strategies balance accuracy with reduced patient burden.
Background:
Glomerular filtration rate in patients can be determined by estimating the plasma clearance of inulin with the single-injection method. In this method, a single bolus injection of inulin is administered and several blood samples are collected. For practical and convenient application of this method in children, it is important that a minimal number of samples are drawn. The aim of this study was to develop and validate sampling strategies with fewer samples for reliable prediction of inulin clearance in pediatric patients by the inulin single-bolus-injection method.
Methods:
Complete inulin plasma concentration-time curves of 154 patients were divided into an index (n = 100) and a validation set (n = 54). A population pharmacokinetic model was developed for the index set. Optimal sampling times were selected based on D-optimality theory. For the validation set, Bayesian estimates of clearance were generated using the derived population parameters and concentrations at two to four sampling times. Bayesian estimates of clearance were compared with the individual reference values of clearance.
Results:
The strategies with samples taken at 10/30/90/240 min, 10/30/240 min, 10/90/240 min, 30/90/240 min, and 90/240 min allowed accurate prediction of inulin clearance (bias <3% and not significantly different from 0; imprecision <15%).
Conclusions:
Strategies involving two to four samples, including a sample at 240 min after administration of inulin, in the inulin single-injection method allow accurate prediction of inulin clearance in pediatric patients. Even one blood sample at 240 min showed acceptable performance. The proposed strategies are practical and convenient to children, and reduce repetitive blood sampling without compromising accuracy.
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