Ann Lab Med.  2023 Nov;43(6):565-573. 10.3343/alm.2023.43.6.565.

Effect of Two Cystatin C Reagents and Four Equations on Glomerular Filtration Rate Estimations After Standardization

• Lee HS
• Bae GE
• Lee JE
• Park HD

• KMID: 2552028
• DOI: http://doi.org/10.3343/alm.2023.43.6.565

Abstract

Background
Serum cystatin C (cysC), which is less affected by sex, race, and muscle mass than creatinine, is a useful biomarker of the estimated glomerular filtration rate (eGFR). The standardization of cysC measurements remains controversial, although a certified reference material (ERM-DA471/IFCC) is available. Moreover, the effect of combinations of cysC reagents and equations for eGFR is unclear.
Methods
We conducted a simulation analysis of cysC measured using two reagents standardized against ERM-DA471/IFCC—Gentian cystatin C immunoassay (Gentian_cys; GentianAS, Moss, Norway) and Roche Tina-quant Cystatin C Gen.2 (Roche_cys; Roche, Mannheim, Germany)—on a Cobas c702 system (Roche) and eGFR generated by eight combinations of four equations: 2012 cystatin C-based Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI_cys); the Caucasian, Asian, pediatric, and adult equation (CAPA_eq); full age spectrum equation (FAS_eq); and 2023 cystatin C-based European Kidney Function Consortium equation (EKFC_cys).
Results
A total of 148 participants (mean age, 60.5±14.5 years; 43% female) were enrolled. The mean cysC was 1.72±1.44 mg/L for Gentiancys and 1.71±1.35 mg/L for Roche_cys. Regression analysis showed concordance between the reagents within 0.85–4.40 mg/L when using ±7.61% total allowable error. Lin’s concordance correlation coefficient of eGFR, by combining the measuring system and equation, varied from 0.73 to 1.00.
Conclusions
The equivalence of cysC values at low concentrations (<0.85 mg/L) between the two reagents was unsatisfactory. Results obtained with different measurement systems could lead to larger differences in eGFR varying with the combination.

Keyword

Cystatin C; Estimated glomerular filtration rate; Chronic Kidney Disease Epidemiology Collaboration; Caucasian; Asian; European Kidney Function Consortium

Figure

• 

  Fig. 1 Bland–Altman plots of cysC values between Gentiancys and Rochecys (A) and the regression line between Gentiancys and Rochecys (B). The Y-axis of (A) is the percentage difference of cysC values between Gentiancys and Rochecys. Abbreviations: cysC, cystatin C; Gentiancys, Gentian cystatin C immunoassay; Rochecys, Tina-quant Gen.2 analysis.

• 

  Fig. 2 Regression lines (A and B) and Bland–Altman plots (C and D) of eGFR values between Gentianeq and CKD-EPIcys using cysC values with Gentiancys and Rochecys. The Y-axes of (C) and (D) are the differences in eGFR between Gentianeq and CKD-EPIcys. Abbreviations: eGFR, estimated glomerular filtration rate; cysC, cystatin C; Gentiancys, Gentian cystatin C immunoassay; Rochecys, Tina-quant Gen.2 analysis; Gentianeq, equation of Gentian manufacturer; CKD-EPIcys, CKD-EPI cystatin C equation.

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