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. 2020 Dec 7;6(2):429-436.
doi: 10.1016/j.ekir.2020.11.028. eCollection 2021 Feb.

GFR Estimation After Cystatin C Reference Material Change

Stefanie W Benoit  1   2   3 , Thelma Kathman  1 , Jay Patel  1 , Melinda Stegman  1 , Cristina Cobb  1 , Jonathan Hoehn  4 , Prasad Devarajan  1   3 , Edward J Nehus  1   3
Affiliations

GFR Estimation After Cystatin C Reference Material Change

Stefanie W Benoit et al. Kidney Int Rep. .

Abstract

Introduction: Glomerular filtration rate (GFR) is routinely estimated with cystatin C. In June 2010, the International Federation of Clinical Chemistry (IFCC) released a certified cystatin C reference material (ERM-DA471/IFCC), and new cystatin C glomerular filtration rate estimation (eGFR) equations were developed with the IFCC standard. Early in 2018, Siemens discontinued their nonstandardized cystatin C reagent kits and replaced them with IFCC-calibrated kits in the US market. The aim of the current study was to assess the effect of IFCC calibration on cystatin C values and corresponding GFR estimations.

Methods: Cystatin C concentration was measured in 81 pediatric patients using a plasma sample from their nuclear GFR measurement with 99mTc-diethylenetriaminepentaaccetic acid. Calibration curves were generated using Siemens nonstandardized and IFCC-standardized kits to measure paired cystatin C concentrations in each sample. GFR-estimating equations using pre-IFCC and IFCC cystatin C values were compared using Bland-Altman analyses.

Results: The IFCC-standardized assay resulted in a mean increase in the measured cystatin C value of 24%. Estimating equations consistently overestimated GFR prior to IFCC standardization. Following incorporation of the IFCC standard, the Full Age Spectrum equation demonstrated the best overall performance, whereas the Chronic Kidney Disease in Children (CKiD) equation was more accurate in children with decreased GFR.

Conclusion: Incorporation of the IFCC standard significantly increased cystatin C values and affected the performance of GFR estimating equations. Clinical laboratories and providers may need to update the equation used for cystatin C-based estimation of GFR following adoption of the IFCC reference standard.

Keywords: clinical laboratory; cystatin C; equations; glomerular filtration rate; pediatric.

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Figures

Figure 1
Figure 1
Pre- and post–International Federation of Clinical Chemistry (IFCC) calibration cystatin C values. (a) Linear regression analysis comparing cystatin C values obtained using the IFCC-calibrated and pre–IFCC calibration reagents (r = 0.998). (b) Bland-Altman plot of IFCC-calibrated cystatin C. Pre–IFCC calibration cystatin C shows a larger difference between pre- and postcalibrated values as the cystatin C value increased. Cystatin C is measured in milligrams per liter. CI, confidence interval.
Figure 2
Figure 2
Bland-Altman plots of eGFRs using pre- and post–International Federation of Clinical Chemistry (IFCC) cystatin C values. Bland-Altman plots of estimated glomerular filtration rate (eGFR) using the IFCC-calibrated cystatin C value: the eGFR using the pre-IFCC calibration cystatin C value for each evaluated equation. Dark blue dashed line is the mean difference. Light blue dashed lines are upper and lower 95% confidence intervals. eGFR is calculated in milliliters per minute per 1.73 m2. CAPA, Caucasian, Asian, pediatric and adult; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CKiD, Chronic Kidney Disease in Children; FAS, full age spectrum.
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