Comparison of three different cystatin C measurement procedures in a pediatric chronic kidney disease cohort: Calibration for longitudinal measurements and implications for clinical estimation of GFR

Introduction: Serum cystatin C (CysC) is used to estimate glomerular filtration rate (eGFR), including in the Chronic Kidney Disease in Children (CKiD) Under 25 years (U25eGFR) equations. Several CysC measurement procedures available from diagnostic vendors include reference material for calibration, but the extent of heterogeneity across manufacturers is unclear. Since heterogeneity may have clinical and research implications for eGFR, we evaluated three CysC procedures in samples from the CKiD study representing a wide spectrum of kidney function. Materials and Methods: The three CysC measurement procedures evaluated were: Siemens BN II N Latex CystatinC Assay; Gentian CystatinC Immunoassay; and Roche Tina-quant CystatinC Gen.2. Bland-Altman quantified agreement with Siemens as reference because that method was used for longitudinal CKiD samples from 2003 to 2023. We present derivation of the interquartile range (IQR) of U25eGFR as a measure of precision and describe differences outside this range. Results: From 53 samples from 44 participants, Gentian measurements were 7 % higher than Siemens (95 %CI: +5.6 %,+8.5 %), while Roche measurements were 4.8 % lower on average (95 %CI:-6.2 %,-3.3 %). Both had very high correlation: 0.9926 and 0.9906, respectively. There was strong agreement across procedures, but a simple correction factor of 7 % reduction applied to Gentian yielded unbiased estimates (+0.03 %, 95 %CI:-1.3 %,+1.4 %) and strong performance in Deming regression. For precision, 98 % of U25eGFR values based on Gentian and Roche CysC were each within the IQR of the Siemens-based estimates. Conclusions: Despite reference material calibration, heterogeneity across CysC measurement procedures was observed. Procedure variability was within the limits of U25eGFR estimates indicating that practically, all procedures are appropriate for clinical use. Clinicians may consider calculating IQR of U25eGFR estimates for pediatric chronic kidney disease management.