Modeling the variability of creatinine measurements improves estimates of the glomerular filtration rate.
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.
Séronie-Vivien
Sophie
S
Department of Clinical Biology, Institut Claudius Regaud, Université Paul Sabatier, Toulouse, France. seronie-vivien.sophie@claudiusregaud.fr
Bouissou
François
F
Dattez
Sophie
S
Coulais
Yvon
Y
Hanser
Anne-Marie
AM
Hym
Bernadette
B
Chatelut
Etienne
E
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007223:Infant; D008297:Male
D003404:Creatinine