Performance in Measurement of Serum Cystatin C by Laboratories Participating in the College of American Pathologists 2014 CYS Survey

Abstract

Context Cystatin C is becoming an increasingly popular biomarker for estimating glomerular filtration rate, and accurate measurements of cystatin C concentrations are necessary for accurate estimates of glomerular filtration rate. Objective To assess the accuracy of cystatin C concentration measurements in laboratories participating in the College of American Pathologists CYS Survey. Design Two fresh frozen serum pools, the first from apparently healthy donors and the second from patients with chronic kidney disease, were prepared and distributed to laboratories participating in the CYS Survey along with the 2 usual processed human plasma samples. Target values were established for each pool by using 2 immunoassays and ERM DA471/IFCC international reference material. Results For the normal fresh frozen pool (ERM-DA471/IFCC–traceable target of 0.960 mg/L), the all-method mean (SD, % coefficient of variation [CV]) reported by all of the 123 reporting laboratories was 0.894 mg/L (0.128 mg/L, 14.3%). For the chronic kidney disease pool (ERM-DA471/IFCC–traceable target of 2.37 mg/L), the all-method mean (SD, %CV) was 2.258 mg/L (0.288 mg/L, 12.8%). There were substantial method-specific biases (mean milligram per liter reported for the normal pool was 0.780 for Siemens, 0.870 for Gentian, 0.967 for Roche, 1.061 for Diazyme, and 0.970 for other/not specified reagents; and mean milligram per liter reported for the chronic kidney disease pool was 2.052 for Siemens, 2.312 for Gentian, 2.247 for Roche, 2.909 for Diazyme, and 2.413 for other/not specified reagents). Conclusions Manufacturers need to improve the accuracy of cystatin C measurement procedures if cystatin C is to achieve its full potential as a biomarker for estimating glomerular filtration rate.

Cystatin C standardization decreases assay variation and improves assessment of glomerular filtration rate

“…Based on the current literature, it is possible that calibration could be applied differently in the US, as it has been speculated for the Siemens assay [13;20-22]. Globally, the studies about cysC calibration show better concordance in European studies, including ours, [10;19;34;35] than in American ones [20][21][22]. However, this hypothesis should be addressed in future studies.…”

Using Glomerular Filtration Rate Estimating Equations: Clinical and Laboratory Considerations

“…On the other hand, the international reference standard for cystatin C has been developed only recently, and not all commercial assays are sufficiently well standardized for routine clinical use (7,8 ). Second, the CKD-EPI equations can be computed from variables that are generally available in clinical and laboratory information systems (age and sex in addition to serum concentrations of creatinine and cystatin C, with separate values reported for African-American individuals) (9 ).…”

Comparing Newer GFR Estimating Equations Using Creatinine and Cystatin C to the CKD-EPI Equations in Adults

“…Bias may reflect differences among assays for creatinine or cystatin C despite standardization 6,11 or among mGFR methods in the study populations used to develop and validate the equations. 12,13 In particular, the larger bias of the LMR versus CKD-EPI creatinine equation (larger underestimation of mGFR) may reflect use of plasma iohexol clearance for development of the LMR equation, which is thought to be lower Figure 1.…”