Cystatin C is recognized as a useful marker for kidney damage. Several equations have been developed to estimate eGFR from serum cystatin C. Because cystatin C measurement procedures do not produce uniform results, the estimating equations are restricted for use only with results from the specific method used to develop them. Consequently, there was a need to standardize cystatin C calibration to enable more widespread use of eGFR estimating equations that use cystatin C concentration in the calculation.
The International Federation of Clinical Chemistry and Laboratory Medicine/Institute for Reference Materials and Measurements working group for standardization of cystatin C (WG-SCC 8.3.37) has taken steps toward standardization.
A cystatin C in human serum reference material (ERM-DA471/IFCC), which is based on SI units (mg/L), is now available from IRMM in Belgium. It is expected this reference material will be listed by the Joint Committee for Traceability in Laboratory Medicine in 2012. It was produced by adding recombinant cystatin C that is identical to the human protein into a serum pool from blood donors. The final product is lyophilized. The value was assigned against the primary reference material of isolated recombinant cystatin C, whose concentration was established by dry mass analysis.
Three different immunochemical techniques were used to transfer the value from the secondary serum calibrator to the first reference preparations: enzyme amplified single radial immunodiffusion (two studies), turbidimitry (three studies), and nephelometry (two studies). Based on these studies, the assigned value and uncertainty is 5.48 +/- 0.15 mg/L (expanded uncertainty with a coverage factor k=2).
As of July 2010, the certificate of analysis does not discuss commutability because the larger scale commutability study is still ongoing.
Preliminary studies have been performed with dilutions of the calibrator and patient samples with a range of cystatin C concentrations. Results are expected to be published in 2011.
ERM-DA471/IFCC has shown good commutability at 60% and greater dilution of the material with 3 immunoassays. This dilution will allow calibration to approximately 3 mg/L, which will cover the 1-2 mg/L range of most interest. The material should not be used undiluted to calibrate methods at higher concentrations unless commutability with patient samples has been confirmed.
Continuing studies of a larger group of measurement procedures indicate that there is acceptable commutability for 11 of the 14 methods tested.
ERM-DA471/IFCC is expected to be used by all manufacturers; one major manufacturer has already made changes to its method to achieve commutability between the reference material and patient samples.
The following publication describes a method for establishing calibration traceability for routine methods to a human serum based reference material: Blirup-Jensen S, Johnson AM, Larsen M. Protein standardization V: Value transfer. A practical protocol for the assignment of serum protein values from a reference material to a target material. Clin Chem Lab Med 2008;46:1470-9.