Cystatin C Standardization
(Update as of January 2014)
A human serum certified reference material for cystatin C has been developed by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)/Institute for Reference Materials and Measurements (IRMM) working group for standardization of cystatin C1.
Certified reference material for cystatin C: ERM-DA471/IFCC
- ERM-DA471/IFCC is available from the Institute for Reference Materials and Measurements in Belgium (http://irmm.jrc.ec.europa.eu/ ).
- The reporting units for cystatin C should be mg/L (SI units).
- As reported in reference (a) below published in 2010, ERMDA471/IFCC and dilutions prepared using the assay diluents were shown to be commutable for combinations of the Siemens N Latex cystatin C Test Kit run on a BN ProSpec (Siemens Healthcare Diagnostics), the Sentinel CH assay run on an Architect c16000 (Abbott Laboratories), and the Gentian cystatin C immunoassay performed on an Architect ci8200.
- The commutability of ERM-DA471/IFCC for use with additional manufacturer’s measurement procedures is being evaluated but this information is not yet available in a peer reviewed report.
Questions concerning the standardization process can be directed to firstname.lastname@example.org.
Estimated GFR based on standardized cystatin C values
Equations to estimate eGFR are now being published that are based on standardized cystatin C values. These equations differ because they are based on data derived from different populations. The equation appropriate for use in a given clinical setting will need to be evaluated based on the similarity between the population being managed for kidney disease and those used in development of an estimating equation. NKDEP recommends that eGFR based on cystatin C use an equation that was developed using data from measurement procedures that were standardized to the ERM-DA471/IFCC certified reference material. It is necessary to contact the in-vitro diagnostics manufacturer of a cystatin C measurement procedure to inquire about the calibration traceability of their procedure.
Conference: Improving GFR Estimates based on Cystatin C for International Use
A conference was organized in February 2013 by the NKDEP Laboratory Working Group and members of the former IFCC Working Group for Standardization of Cystatin C to discuss improving GFR estimates based on standardized cystatin C. The conference was hosted by Dr. Anders Grubb, chair of the IFCC working group, in Lund, Sweden. Fifty-four clinical laboratory scientists, nephrologists and IVD industry scientists from 10 countries participated in the conference.
In preparation for the conference, three research teams (the Chronic Kidney Disease Epidemiology Collaboration in the USA, the IFCC group in Sweden and the group of Dr. Horio in Japan) agreed to assess comparability of cystatin C measurement procedures used by each group and to perform comparisons of estimating equation performance across datasets, including unpublished data. In all cases, the estimating equations were based on cystatin C measurements that had calibration traceable to ERM-DA471/IFCC certified reference material. Similarly, creatinine measurements were all traceable to IDMS reference measurement procedures.
The Swedish Council on Health Technology Assessment has recently completed an evidence- based review of methods used to measure and to estimate GFR. It was reassuring to learn that both iohexol and iothalamate-based approaches to measure GFR agreed well with traditional inulin based “gold standard” procedures. There were differences based on the details of filtration marker administration and sampling, but overall it appeared that measured GFR by any of the techniques is acceptable to use as a reference for evaluating the performance of the estimating equations.
Performance of estimating equations compared to measured GFR varied across populations, probably reflecting demographic and clinical characteristics of the study populations and methods to measure GFR. As expected, the estimating equations performed best when applied to populations most similar to those used to develop each equation. Inclusion or exclusion of age and gender factors in cystatin C based equations may partially explain differences observed in some populations. It is worth noting that all estimating equations using either creatinine or cystatin C had noticeable imprecision, which was improved by including both cystatin C and creatinine in an equation.
There was agreement that it is desirable to identify generally applicable estimating equations and to understand their limitations. The data will be examined in greater detail to address comments made during the conference and to determine if additional research may be needed.
The IVD industry should proceed to implement standardized cystatin C measurement procedures with results traceable to the ERM-DA471/IFCC certified reference material. Standardized cystatin C results are a prerequisite to general use of any GFR estimating equation based on cystatin C.
April 2, 2014