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Updated: Jul 9, 2026
A High-throughput Method for Measurement of Glomerular Filtration Rate in Conscious Mice
Published on: May 10, 2013
Modeling the variability of creatinine measurements improves estimates of the glomerular filtration rate
Sophie Séronie-Vivien1, François Bouissou, Sophie Dattez
1Department of Clinical Biology, Institut Claudius Regaud, Université Paul Sabatier, Toulouse, France. seronie-vivien.sophie@claudiusregaud.fr
Insights
Serum creatinine (SCr) assay bias affects glomerular filtration rate (GFR) estimation. Population pharmacokinetics modeling can adjust for SCr assay variability, improving GFR accuracy in children when assays are not standardized.
Area of Science:
- Pediatric Nephrology
- Clinical Chemistry
- Pharmacokinetics
Background:
- Estimating glomerular filtration rate (GFR) relies on formulae sensitive to serum creatinine (SCr) assay biases.
- Discrepancies between SCr assay methods and those used in formula development reduce GFR estimation precision.
Purpose of the Study:
- To evaluate the impact of different serum creatinine (SCr) assay methods on GFR estimation in children.
- To develop a population pharmacokinetics model to correct for SCr assay variability in GFR calculations.
Main Methods:
- Serum creatinine (SCr) was measured in 100 children using JAFFE, compensated Jaffe (COMP), enzymatic (ENZ), and HPLC assays.
- 51Cr-EDTA clearance (CLEDTA) was used as the reference for GFR.
- A non-linear mixed effects model (NONMEM) was employed for population pharmacokinetics analysis.
Main Results:
- The Schwartz formula showed significant positive bias for GFR when using COMP (+27.0%) and ENZ (+39.1%) SCr assays compared to JAFFE.
- A novel GFR equation was derived using NONMEM: CLEDTA (mL/min)=61.9 x [SCr (microM)/Theta]Psi x [age (years)/13.4]0.522 x (weight (kg)/44.2)0.233.
- This new equation accurately estimated CLEDTA in a separate cohort, with minimal bias for COMP (+3.1%) and ENZ (+5.3%) assays.
Conclusions:
- Serum creatinine (SCr) assay standardization is crucial for accurate GFR estimation.
- Population pharmacokinetics modeling offers a robust method to address inter-assay variability in SCr measurements.
- This approach can improve GFR accuracy in pediatric populations when standardized SCr assays are unavailable.
Background:
The precision of the formulae used to estimate glomerular filtration rate (GFR) decreases when the serum creatinine (SCr) assay is biased compared with the assay used during the development of the formulae.
Methods:
For 100 children referred for 51Cr-EDTA clearance (CLEDTA), SCr was measured with a JAFFE (classic Jaffe colorimetric creatinine assay), a compensated Jaffe (COMP), an enzymatic (ENZ) and an HPLC assay. A population pharmacokinetics approach based on a non-linear mixed effects model (NONMEM) was used to model the relationships between the CLEDTA and physiopathological/analytical variables.
Results:
Unlike JAFFE values, COMP and ENZ SCr gave a high bias using the Schwartz formula for the GFR calculation (median +27.0% and +39.1%, respectively). The best equation obtained from the analysis of the curves of [51Cr-EDTA]plasma vs. time was (n=67): CLEDTA (mL/min)=61.9 x [SCr (microM)/Theta]Psi x [age (years)/13.4]0.522 x (weight (kg)/44.2)0.233. The SCr assay-related coefficients and exponents were Theta=97.4, Psi=-0.757 (-0.922; -0.592) for JAFFE; Theta=85.3, Psi=-0.579 (-0.681; -0.477) for COMP; and Theta=82.6, Psi=-0.560 (-0.659; -0.460) for ENZ. When applied to 33 children, this equation estimated CL(EDTA) without any significant bias: +3.1% (-11.8; +11.4) for COMP and +5.3% (-7.2; +16.4) for ENZ.
Conclusions:
As long as there is no standardization of SCr measurements, population pharmacokinetics may be a powerful tool to model inter-assay variability.
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