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Iohexol plasma clearance in children: validation of multiple formulas and single-point sampling times
Camilla Tøndel1,2, Cathrin Lytomt Salvador3,4, Karl Ove Hufthammer5
1Department of Pediatrics, Haukeland University Hospital, 5021, Bergen, Norway. camilla.tondel@helse-bergen.no.
Insights
The Fleming formula at 3 hours (GFR1p3h-Fleming) accurately estimates glomerular filtration rate (GFR) in children with CKD and GFR ≥ 30 mL/min/1.73 m2, offering a simpler alternative to two-point methods. For lower GFRs, multiple blood samples are recommended.
Area of Science:
- Pediatric Nephrology
- Diagnostic Imaging
- Biomarker Analysis
Background:
- Iohexol is a preferred non-ionic agent for glomerular filtration rate (GFR) measurement.
- Accurate GFR estimation in children is challenging, necessitating methods that minimize blood draws.
- This study evaluates single-time-point GFR formulas using iohexol clearance in pediatric chronic kidney disease (CKD).
Purpose of the Study:
- To assess the accuracy of various single-point formulas for calculating measured GFR (mGFR) based on plasma iohexol clearance.
- To identify the optimal blood sampling time point for single-point GFR estimation in children.
- To compare single-point GFR methods with a reference multi-point method.
Main Methods:
- A cross-sectional study involving 96 children with CKD stages 1-5.
- Iohexol clearance measured with seven blood samples within 5 hours (GFR7p) served as the reference.
- Six single-point GFR formulas were validated against the GFR7p reference.
Main Results:
- The Fleming formula with a single blood draw at 3 hours (GFR1p3h-Fleming) demonstrated the best performance, with 82% of values within 10% of the reference (P10).
- In children with GFR ≥ 30 mL/min/1.73 m2, GFR1p3h-Fleming achieved 92.3% P10, comparable to the two-point method (96.2%).
- Significant variations in formula performance were observed across different CKD stages and sampling times.
Conclusions:
- GFR1p3h-Fleming is recommended as a reliable single-point method for estimating mGFR in children with CKD and GFR ≥ 30 mL/min/1.73 m2.
- For children with GFR < 30 mL/min/1.73 m2, slope-GFR using at least two blood samples is advised.
- These findings support optimized GFR measurement protocols in pediatric nephrology.
Background:
The non-ionic agent iohexol is increasingly used as the marker of choice for glomerular filtration rate (GFR) measurement. Estimates of GFR in children have low accuracy and limiting the number of blood-draws in this patient population is especially relevant. We have performed a study to evaluate different formulas for calculating measured GFR based on plasma iohexol clearance with blood sampling at only one time point (GFR1p) and to determine the optimal sampling time point.
Methods:
Ninety-six children with chronic kidney disease (CKD) stage 1-5 (median age 9.2 years; range 3 months to 17.5 years) were examined in a cross-sectional study using iohexol clearance and blood sampling at seven time points within 5 h (GFR7p) as the reference method. Median GFR7p was 66 (range 6-153) mL/min/1.73 m2. The performances of six different single time-point formulas (Fleming, Ham and Piepsz, Groth and Aasted, Stake, Jacobsson- and Jacobsson-modified) were validated against the reference. The two-point GFR (GFR2p) was calculated according to the Jødal and Brøchner-Mortensen formula.
Results:
The GFR1p calculated according to Fleming with sampling at 3 h (GFR1p3h-Fleming) had the best overall performance, with 82% of measures within 10% of the reference value (P10). In children with a GFR ≥ 30 mL/min/1.73 m2 (n = 78), the GFR1p3h-Fleming had a P10 of 92.3%, which is not significantly different (p = 0.29) from that of GFR2p (P10 = 96.2%). Considerable differences within and between the different formulas were found for different CKD stages and different time points for blood sampling.
Conclusions:
For determination of mGFR in children with CKD and an assumed GFR of ≥ 30 mL/min/1.73 m2 we recommend GFR1p3h-Fleming as the preferred single-point method as an alternative to GFR2p. For children with a GFR < 30 mL/min/1.73 m2, we recommend the slope-GFR with at least two blood samples.
Clinical Trial Registration:
ClinicalTrials.gov , Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2.
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