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Prime Time for Enzymatic Creatinine Methods in Pediatrics

¹ Department of Clinical Chemistry, Amphia Hospital, Breda; ² SKML, UMC St-Radboud, Nijmegen; ³ Department of Clinical Chemistry, Queen Beatrix Hospital, Winterswijk, The Netherlands.

^aAddress correspondence to this author at: Amphia Hospital, Department of Clinical Chemistry and Hematology, Location Molengracht, Molengracht 21, 4800 RK Breda, The Netherlands. E-mail ccobbaert{at}amphia.nl, c.cobbaert{at}planet.nl.

Background: The literature regarding the nonspecificity of applications of the Jaffe (alkaline picrate) reaction for creatinine is generally outdated. We conducted a specificity study to update the nonspecificity information for current Jaffe and enzymatic creatinine assays.

Methods: Two serum pools with creatinine concentrations within the pediatric reference interval were spiked with albumin, IgG, unconjugated bilirubin, adult hemoglobin (Hb A), and fetal hemoglobin (Hb F) to produce 1 unspiked and 5 spiked samples per pool. The 35 laboratories participating in the survey used a total of 14 method–analyzer combinations. Measurements were performed in triplicate in a single run in accordance with manufacturer instructions. Absolute differences in creatinine concentration between spiked and unspiked samples were calculated per laboratory. Mixed ANOVA was used to quantify the interferent-related CV component for the Jaffe and enzymatic methods.

Results: The interference by bilirubin and Hb A on serum creatinine measurements was <10% for most of the Jaffe and enzymatic methods. Obvious interference was observed among the Jaffe methods in samples spiked with Hb F, albumin, and IgG, but not among the enzymatic methods. The within-laboratory interferent-related CVs for the Jaffe method–analyzer combinations ranged from 8.0%–27% at a creatinine concentration of 40.4 µmol/L (0.46 mg/dL) and from 5.4%–15% at 73.4 µmol/L (0.83 mg/dL). Enzymatic methods had within-laboratory interferent-related CVs of <4% at both concentrations.

Conclusions: Albumin, IgG, and Hb F interfered with Jaffe creatinine assays, leading to inaccuracies in estimated glomerular filtration rates that are clinically important, especially in children and neonates. Because protein error and Hb F interference do not occur with any of the enzymatic methods tested, we conclude that enzymatic creatinine methods are preferred for evaluation of kidney function in pediatric cases.

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