Natalie Ebert1, Pierre Delanaye2, Michael Shlipak3, Olga Jakob4, Peter Martus5, Jan Bartel6, Jens Gaedeke7, Markus van der Giet8, Mirjam Schuchardt8, Etienne Cavalier9, Elke Schaeffner10. 1. Charité University Medicine, Institute of Public Health, Berlin, Germany. Electronic address: natalie.ebert@charite.de. 2. Division of Nephrology, Centre Hospitalier Universitaire du Sart-Tilman, Liège, Belgium. 3. San Francisco VA Medical Center, San Francisco, USA; University of California, San Francisco, USA. 4. Institute of Biostatistics and Clinical Epidemiology, Charité, Berlin, Germany. 5. Institute of Clinical Epidemiology and Medical Biostatistics, University Tübingen, Germany. 6. Limbach Laboratory, Heidelberg, Germany. 7. Division of Nephrology, Charité University Medicine, Campus Mitte, Berlin, Germany. 8. Division of Nephrology, Charité University Medicine, Campus Benjamin Franklin, Berlin, Germany. 9. Department of Clinical Chemistry, Centre Hospitalier Universitaire du Sart-Tilman, Liège, Belgium. 10. Charité University Medicine, Institute of Public Health, Berlin, Germany.
Abstract
BACKGROUND: Cystatin C is increasingly used in glomerular filtration rate (GFR) estimation equations. The dependence of cystatin C results upon the analytical method has been a major source of controversy. METHODS: Cystatin C was measured with non-standardized turbidimetric Roche Generation 1 and standardized nephelometric Siemens assays in 3666 and additionally with standardized Roche Generation 2 and Siemens in 567 blood samples of the Berlin Initiative Study. Cystatin C-based GFR was assessed with CKD-EPIcys (Chronic Kidney Disease Epidemiology) and CAPA (Caucasian, Asian, Pediatric, Adult) equations and the impact of the assays on GFR estimation was determined. Equation performance compared to measured GFR was evaluated. RESULTS: Concordance of Roche Gen2 and Siemens was high with median difference of 0.003 ± 0.13 mg/L (limits of agreement: -0.12 to 0.12) and Passing Bablok correlation was essentially perfect. Roche Gen1 assay showed worse concordance with Siemens: median difference was 0.08 ± 0.13 mg/L (limits of agreement: -0.18 to 0.34) and correlation was inferior. Mean difference (± SD) of estimated GFRCKD-EPIcys was 0 ± 4 mL/min/1.73 m(2) for Gen2 and Siemens compared to -5 ± 8 with Gen1. Performance of GFR estimating equations was not influenced by the choice of Siemens or Gen2 assays. CONCLUSIONS: Standardization of Roche Gen2 assay improved accuracy of cystatin C measurement compared to Siemens. It suggests only negligible method bias and results in equal performance of both assays when estimating GFR indicating that successful calibration has led to major progress in cystatin C analysis.
BACKGROUND:Cystatin C is increasingly used in glomerular filtration rate (GFR) estimation equations. The dependence of cystatin C results upon the analytical method has been a major source of controversy. METHODS:Cystatin C was measured with non-standardized turbidimetric Roche Generation 1 and standardized nephelometric Siemens assays in 3666 and additionally with standardized Roche Generation 2 and Siemens in 567 blood samples of the Berlin Initiative Study. Cystatin C-based GFR was assessed with CKD-EPIcys (Chronic Kidney Disease Epidemiology) and CAPA (Caucasian, Asian, Pediatric, Adult) equations and the impact of the assays on GFR estimation was determined. Equation performance compared to measured GFR was evaluated. RESULTS: Concordance of Roche Gen2 and Siemens was high with median difference of 0.003 ± 0.13 mg/L (limits of agreement: -0.12 to 0.12) and Passing Bablok correlation was essentially perfect. Roche Gen1 assay showed worse concordance with Siemens: median difference was 0.08 ± 0.13 mg/L (limits of agreement: -0.18 to 0.34) and correlation was inferior. Mean difference (± SD) of estimated GFRCKD-EPIcys was 0 ± 4 mL/min/1.73 m(2) for Gen2 and Siemens compared to -5 ± 8 with Gen1. Performance of GFR estimating equations was not influenced by the choice of Siemens or Gen2 assays. CONCLUSIONS: Standardization of Roche Gen2 assay improved accuracy of cystatin C measurement compared to Siemens. It suggests only negligible method bias and results in equal performance of both assays when estimating GFR indicating that successful calibration has led to major progress in cystatin C analysis.
Authors: George J Schwartz; Christopher Cox; Jesse C Seegmiller; Paula S Maier; Donna DiManno; Sue L Furth; Bradley A Warady; Alvaro Munoz Journal: Pediatr Nephrol Date: 2019-11-03 Impact factor: 3.714
Authors: Elke S Schaeffner; Natalie Ebert; Martin K Kuhlmann; Peter Martus; Nina Mielke; Alice Schneider; Markus van der Giet; Dörte Huscher Journal: Clin J Am Soc Nephrol Date: 2022-07-18 Impact factor: 10.614
Authors: Justine B Bukabau; Ernest K Sumaili; Etienne Cavalier; Hans Pottel; Bejos Kifakiou; Aliocha Nkodila; Jean Robert R Makulo; Vieux M Mokoli; Chantal V Zinga; Augustin L Longo; Yannick M Engole; Yannick M Nlandu; François B Lepira; Nazaire M Nseka; Jean Marie Krzesinski; Pierre Delanaye Journal: PLoS One Date: 2018-03-02 Impact factor: 3.240
Authors: S Ali Husain; Joshua Z Willey; Yeseon Park Moon; Mitchell S V Elkind; Ralph L Sacco; Myles Wolf; Ken Cheung; Clinton B Wright; Sumit Mohan Journal: PLoS One Date: 2018-11-14 Impact factor: 3.240
Authors: Stefanie W Benoit; Thelma Kathman; Jay Patel; Melinda Stegman; Cristina Cobb; Jonathan Hoehn; Prasad Devarajan; Edward J Nehus Journal: Kidney Int Rep Date: 2020-12-07