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

Area of Science:

• Clinical Chemistry
• Biomarker Analysis
• Renal Function Assessment

Background:

• Serum cystatin C (cysC) is a reliable biomarker for estimated glomerular filtration rate (eGFR), less influenced by factors like sex and muscle mass compared to creatinine.
• Standardization of cysC measurements faces challenges despite available certified reference materials.
• The impact of combining different cysC reagents and eGFR equations remains unclear.

Purpose of the Study:

• To evaluate the concordance of cysC measurements between two standardized reagents (Gentian_cys and Roche_cys).
• To assess the variability in eGFR estimations generated by combining these cysC measurements with four different equations (CKD-EPI_cys, CAPA_eq, FAS_eq, EKFC_cys).

Main Methods:

• A simulation analysis was performed on cysC measurements from 148 participants using Gentian_cys and Roche_cys reagents.
• eGFR was calculated using eight combinations of two cysC measurement results and four distinct equations.
• Statistical analyses included regression and Lin's concordance correlation coefficient to assess agreement.

Main Results:

• Mean cysC levels were comparable between Gentian_cys (1.72±1.44 mg/L) and Roche_cys (1.71±1.35 mg/L).
• Reagent concordance was observed within 0.85-4.40 mg/L under a ±7.61% total allowable error.
• Lin's concordance correlation coefficient for eGFR varied significantly (0.73 to 1.00) depending on the reagent-equation combination.

Conclusions:

• Equivalence of cysC values between the two reagents was unsatisfactory at low concentrations (<0.85 mg/L).
• Different measurement systems and equation combinations can lead to substantial variations in calculated eGFR.
• These findings underscore the need for improved standardization in cysC assays for accurate eGFR determination.