Analytic and clinical validation of a standardized cystatin C particle enhanced turbidimetric assay (PETIA) to estimate glomerular filtration rate

Background: Cystatin C is an alternative biomarker for assessing glomerular filtration rate (GFR), yet lack of standardization could hinder its widespread use. In this study we analytically and clinically validated a newer cystatin C particle-enhanced turbidimetric assay (PETIA) traceable to a certified reference material and compared it to the more commonly used particle-enhanced nephelometric assay (PENIA). Methods: Samples from four patient cohorts at the Mayo Clinic were studied: 1) clinical convenience samples (n = 50); 2) samples from patients undergoing iothalamate urinary clearance testing for clinical indications (n = 101); 3) volunteers without kidney disease (n = 292); 4) samples from 1999 to 2000 with previous cystatin C measurements. Results: The cystatin C PETIA was analytically robust between 0.15 mg/L and 8.36 mg/L. PETIA cystatin C values were 27.5 % higher than PENIA results. Furthermore, PENIA results were 12.9 % lower in 2010 than in 2000. PETIA cysta-tin C values and existing equations performed reasonably well to estimate GFR with an overall - 7.4 % bias for all patients analyzed. Age and gender specific reference intervals were established for the PETIA cystatin C. Conclusions: Cystatin C can be precisely measured by PETIA traceable to the international reference material, ERM-DA471/IFCC, using a routine chemistry autoanalyzer. There are important biases between this assay and the widely employed Siemens PENIA. This study highlights the importance of assay standardization if cystatin C is to be widely used to estimate GFR.