Long-Term Longitudinal Stability of Kidney Filtration Marker Measurements: Implications for Epidemiological Studies and Clinical Care

Abstract

Background Establishment and improvement of glomerular filtration rate estimating equations requires accurate and precise laboratory measurement procedures (MPs) for filtration markers. The Advanced Research and Diagnostic Laboratory (ARDL) at the University of Minnesota, which has served as the central laboratory for the Chronic Kidney Disease Epidemiology Collaboration since 2009, has implemented several quality assurance measures to monitor the accuracy and stability of filtration marker assays over time. Methods To assess longitudinal stability for filtration marker assays, a 40-sample calibration panel was created using pooled serum, divided into multiple frozen aliquots stored at −80 °C. ARDL monitored 4 markers—creatinine, cystatin C, beta-2-microglobulin (B2M) and beta-trace protein—measuring 15 calibration panel aliquots from 2009 to 2019. Initial target values were established using the mean of the first 3 measurements performed in 2009–10, and differences from target were monitored over time. New MPs for cystatin C and B2M were added in 2012, with target values established using the first measurement. Results The mean percentage difference from mean target values across time was <2% for all original MPs (−0.59% for creatinine; −0.94% for cystatin C; −0.82% for B2M; 1.24% for beta-trace protein). Conclusions Close monitoring of filtration marker trends with a calibration panel at ARDL demonstrates remarkable long-term stability of the MPs. Routine use of a calibration panel for both research studies and clinical care is recommended for filtration markers where longitudinal monitoring is important to detect analytical biases, which can mask or confound true clinical trends in patients.

Association of Estimated GFR Calculated Using Race-Free Equations With Kidney Failure and Mortality by Black vs Non-Black Race

“…Measurement of creatinine and cystatin C followed previously reported methods . Values from each cohort were calibrated to the extent possible using the available information.…”

A prospective cross-sectional study estimated glomerular filtration rate from creatinine and cystatin C in adults with solid tumors

“…Serum samples for creatinine and cystatin C were frozen at -80 C, and measured at the University of Minnesota at the end of the study during a single run, using assays traceable to international reference materials. 16 Other analytes were analyzed locally on the day the samples were collected (Supplementary Material Section SE).…”

Improved Performance in Measurement of Serum Cystatin C by Laboratories Participating in the College of American Pathologists 2019 CYS Survey

“…While performance of cystatin C measurement procedures significantly improved during this 5-year period, caveats and concerns remain. First, despite the improved performance of cystatin C measurement procedures, the accuracy and between-method agreement of cystatin C falls well short of creatinine, 21,22 which is still considered the most widely accepted filtration marker for GFR estimation. Virtually all creatinine measurement procedures have been universally standardized to an isotope-dilution mass spectrometry (IDMS) reference measurement procedure, with a serumbased reference material (SRM 967 from the National Institute of Standards and Technology) available to manufacturers and laboratories that is traceable to IDMS.…”