Improved Performance in Measurement of Serum Cystatin C by Laboratories Participating in the College of American Pathologists 2019 CYS Survey

Abstract

Context.— Use of cystatin C for glomerular filtration rate estimation (eGFR) has garnered heightened interest as a means to avoid race-based medicine, since eGFRcys equations do not require specification of race. Before considering more widespread use of cystatin C, it is important to confirm that assays provide accurate measurements of cystatin C concentration, to ensure accurate GFR estimates. Objective.— To determine if the accuracy of cystatin C measurements in laboratories participating in the College of American Pathologists' (CAP) Cystatin C (CYS) survey has improved since 2014. Design.— Two fresh frozen serum pools, the first from healthy donors without chronic kidney disease (CKD), and the second from patients with CKD, along with a synthetically prepared elevated cystatin C pool, were sent to laboratories participating in the 2019 CYS-A survey. Target values were established by using 2 immunoassays and a bracketed 2-point calibration with diluted ERM-DA471/IFCC reference material. Results.— For the healthy donor fresh frozen pool (ERM-DA471/IFCC-traceable target of 0.725 mg/L), the all-method mean (standard deviation, coefficient of variation) was 0.731 mg/L (0.071, 9.7%). For the CKD pool (ERM-DA471/IFCC-traceable target of 2.136 mg/L), the all-method mean was 2.155 mg/L (0.182, 8.4%). For the synthetically spiked pool (ERM-DA471/IFCC-traceable target of 1.843 mg/L), the all-method mean was 1.886 mg/L (0.152, 8.1%). This represents marked improvement in accuracy and between-method agreement compared to the 2014 CAP survey. Conclusions.— Manufacturers have markedly improved accuracy and between-method agreement of cystatin C measurement procedures since 2014, which allows for greater confidence in estimated GFR relying on cystatin C.

Exploring Renal Function Assessment: Creatinine, Cystatin C, and Estimated Glomerular Filtration Rate Focused on the European Kidney Function Consortium Equation

“…While a certified reference material for cysC (ERM-DA471/IFCC) is available, there are currently no certified reference measurement procedures for cysC to definitively establish target values for the cysC reference material [ 33 ]. However, studies have shown that manufacturers have markedly improved the accuracy and between-method agreement of cysC measurement procedures since 2014, which allows for greater confidence in eGFR relying on cysC [ 34 , 35 ]. For example, standardization of the Roche Gen2 assay improved the accuracy of cysC measurement compared to that of the Siemens assay [ 34 ].…”

“…However, despite the improved performance of cysC measurement procedures, the accuracy and between-method agreement of cysC fall well short of those of creatinine, which still is the most widely accepted filtration marker for GFR estimation. Moreover, while at present, all cysC assay kits are traceable to the ERM-DA471/IFCC reference material, ERM-DA471/IFCC-non-traceable kits were still distributed to users of older Siemens platforms, such as the ADVIA Centaur and Siemens Dimension Vista, until the end of 2020 [ 35 ]. The old Siemens Cystatin C assay for the ADVIA Chemistry and Atellica CH platforms was taken from the market in 2020 and replaced with Cystatin C_2, which is traceable to ERM-DA471 (Siemens private communication).…”

Advantages, Limitations, and Clinical Considerations in Using Cystatin C to Estimate GFR

“…25 However, the 2019 General Chemistry Survey of the College of American Pathologists showed that only 7% of U.S. clinical laboratories offered CysC tests, with >90% of these labs referring CysC testing to external commercial labs. 26 Concerns for assay accuracy and agreement across laboratories have impeded broader clinical CysC adoption. To address these concerns, certified reference materials (ERM-DA471/IFCC), which enable assay manufacturers to calibrate their methods, were made available in 2010.…”

“…In a 2020 survey of a subset of nephrology respondents of the International Society of Nephrology Global Kidney Health Atlas, 67% reported that CysC testing was available within their region (25). However, the 2019 General Chemistry Survey of the College of American Pathologists showed that only 7% of US clinical laboratories offered CysC tests, with >90% of these labs referring CysC testing to external commercial labs (26).…”

“…Similar issues across measurement methods were noted in the 2014 CAP Cystatin C Proficiency Testing Program (28). Conversely, a 2019 study by the same CAP program found much improved accuracy and agreement across CysC measurement methods, with coefficients of variation <10% and biases of <0.9% for healthy and CKD samples (26). Although certified reference measurement procedures are still needed to attain a similar level of confidence in assay performance to that for sCr measurements (26), these recent findings are reassuring as clinical use of CysC grows.…”