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Imprecision remains to be improved in the measurement of serum cystatin C with heterogeneous systems

  • Jie Zeng , Li Zhang , Jiangtao Zhang , Weiyan Zhou ORCID logo , Tianjiao Zhang , Jing Wang , Haijian Zhao and Chuanbao Zhang ORCID logo EMAIL logo
Published/Copyright: March 6, 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 61 Issue 8

Abstract

Objectives

Except for the large bias of some measurement systems for serum cystatin C (CysC) measurements, unacceptable imprecision has been observed for the heterogenous system. This study analyzed the external quality assessment (EQA) results in 2018–2021 to provide an insight into the imprecision of CysC assays.

Methods

Five EQA samples were sent to participating laboratories every year. Participants were divided into reagent/calibrator-based peer groups, for which the robust mean of each sample and robust coefficient of variation (CV) were calculated by Algorithm A from ISO 13528. Peers with more than 12 participants per year were selected for further analysis. The limit of CV was determined to be 4.85% based on clinical application requirements. The concentration-related effect on CVs was investigated using logarithmic curve fitting; the difference in medians and robust CVs between instrument-based subgroups was also evaluated.

Results

The total number of participating laboratories increased from 845 to 1,695 in four years and heterogeneous systems remained the mainstream (≥85%). Of 18 peers with ≥12 participants, those using homogeneous systems showed relatively steady and small CVs over four years, with the mean four-year CVs ranging from 3.21 to 3.68%. Some peers using heterogenous systems showed reduced CVs over four years, while 7/15 still had unacceptable CVs in 2021 (5.01–8.34%). Six peers showed larger CVs at the low or high concentrations, and some instrument-based subgroups presented greater imprecision than others.

Conclusions

More efforts should be made to improve the imprecision of heterogeneous systems for CysC measurement.

Keywords: cystatin C; external quality assessment; imprecision; peer group evaluation
Corresponding author: Chuanbao Zhang, National Center for Clinical Laboratories, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing Engineering Research Center of Laboratory Medicine, Institute of Geriatric Medicine, Beijing, P.R. China, Phone: +86 010-58115059, Fax: +86 010-65132968, E-mail:
Jie Zeng and Li Zhang contributed equally to this work.

Funding source: National Key Research and Development Program of China

Award Identifier / Grant number: 2022YFC3602301

  1. Research funding: National Key Research and Development Program of China: No. 2022YFC3602301.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Not applicable.

References

1. Eckardt, KU, Coresh, J, Devuyst, O, Johnson, RJ, Köttgen, A, Levey, AS, et al.. Evolving importance of kidney disease: from subspecialty to global health burden. Lancet 2013;382:158–69. https://doi.org/10.1016/s0140-6736(13)60439-0.Search in Google Scholar

2. Vijay, P, Lal, BB, Sood, V, Khanna, R, Alam, S. cystatin C: best biomarker for acute kidney injury and estimation of glomerular filtration rate in childhood cirrhosis. Eur J Pediatr 2021;180:3287–95. https://doi.org/10.1007/s00431-021-04076-1.Search in Google Scholar PubMed

3. Lees, JS, Welsh, CE, Celis-Morales, CA, Mackay, D, Lewsey, J, Gray, SR, et al.. Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease. Nat Med 2019;25:1753–60. https://doi.org/10.1038/s41591-019-0627-8.Search in Google Scholar PubMed PubMed Central

4. Casal, MA, Nolin, TD, Beumer, JH. Estimation of kidney function in oncology: implications for anticancer drug selection and dosing. Clin J Am Soc Nephrol 2019;14:587–95. https://doi.org/10.2215/cjn.11721018.Search in Google Scholar PubMed PubMed Central

5. Lameire, NH, Levin, A, Kellum, JA, Cheung, M, Jadoul, M, Winkelmayer, WC, et al.. Harmonizing acute and chronic kidney disease definition and classification: report of a kidney disease: improving global Outcomes (KDIGO) consensus conference. Kidney Int 2021;100:516–26. https://doi.org/10.1016/j.kint.2021.06.028.Search in Google Scholar PubMed

6. Levey, AS, Coresh, J, Tighiouart, H, Greene, T, Inker, LA. Measured and estimated glomerular filtration rate: current status and future directions. Nat Rev Nephrol 2020;16:51–64. https://doi.org/10.1038/s41581-019-0191-y.Search in Google Scholar PubMed

7. Levey, AS, Titan, SM, Powe, NR, Coresh, J, Inker, LA. Kidney disease, race, and GFR estimation. Clin J Am Soc Nephrol 2020;15:1203–12. https://doi.org/10.2215/cjn.12791019.Search in Google Scholar

8. Shlipak, MG, Tummalapalli, SL, Boulware, LE, Grams, ME, Ix, JH, Jha, V, et al.. The case for early identification and intervention of chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2021;99:34–47. https://doi.org/10.1016/j.kint.2020.10.012.Search in Google Scholar PubMed

9. Kashani, K, Rosner, MH, Ostermann, M. Creatinine: from physiology to clinical application. Eur J Intern Med 2020;72:9–14. https://doi.org/10.1016/j.ejim.2019.10.025.Search in Google Scholar PubMed

10. Kimura, K, Morita, H, Daimon, M, Horio, M, Kawata, T, Nakao, T, et al.. Utility of cystatin C for estimating glomerular filtration rate in patients with muscular dystrophy. Int Heart J 2016;57:386–8. https://doi.org/10.1536/ihj.15-461.Search in Google Scholar PubMed

11. Li, DY, Yin, WJ, Zhou, LY, Ma, RR, Liu, K, Hu, C, et al.. Utility of cystatin C-based equations in patients undergoing dialysis. Clin Chim Acta 2018;485:282–7. https://doi.org/10.1016/j.cca.2018.07.010.Search in Google Scholar PubMed

12. Delgado, C, Baweja, M, Crews, DC, Eneanya, ND, Gadegbeku, CA, Inker, LA, et al.. A unifying approach for GFR estimation: recommendations of the NKF-ASN task force on reassessing the inclusion of race in diagnosing kidney disease. J Am Soc Nephrol 2021;32:2994–3015. https://doi.org/10.1681/asn.2021070988.Search in Google Scholar

13. Eckfeldt, JH, Karger, AB, Miller, WG, Rynders, GP, Inker, LA. Performance in measurement of serum cystatin C by laboratories participating in the College of American Pathologists 2014 CYS survey. Arch Pathol Lab Med 2015;139:888–93. https://doi.org/10.5858/arpa.2014-0427-cp.Search in Google Scholar

14. Grubb, A, Horio, M, Hansson, LO, Björk, J, Nyman, U, Flodin, M, et al.. Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator. Clin Chem 2014;60:974–86. https://doi.org/10.1373/clinchem.2013.220707.Search in Google Scholar PubMed

15. Bargnoux, AS, Kuster, N, Delatour, V, Delanaye, P, González-Antuña, A, Cristol, JP, et al.. Reference method and reference material are necessary tools to reveal the variability of cystatin C assays. Arch Pathol Lab Med 2016;140:117–8. https://doi.org/10.5858/arpa.2015-0198-le.Search in Google Scholar

16. Karger, AB, Long, T, Inker, LA, Eckfeldt, JH. Improved performance in measurement of serum cystatin C by laboratories participating in the College of American Pathologists’ 2019 CYS survey. Arch Pathol Lab Med 2022;146:1218–23. https://doi.org/10.5858/arpa.2021-0306-cp.Search in Google Scholar PubMed

17. Bargnoux, AS, Piéroni, L, Cristol, JP, Kuster, N, Delanaye, P, Carlier, MC, et al.. Multicenter evaluation of cystatin C measurement after assay standardization. Clin Chem 2017;63:833–41. https://doi.org/10.1373/clinchem.2016.264325.Search in Google Scholar PubMed

18. China National Accreditation Service for Conformity Assessment. CNAS-GL003: Guidance on evaluating the homogeneity and stability of samples used for proficiency testing. Beijing, China: CNAS; 2018.Search in Google Scholar

19. International Organization for Standardization. ISO 13528: statistical methods for use in proficiency testing by interlaboratory comparison. Geneva, Switzerland: ISO; 2022.Search in Google Scholar

20. Aarsand, AK, Fernandez-Calle, P, Webster, C, Coskun, A, Gonzales-Lao, E, Diaz-Garzon, J, et al.. The EFLM biological variation database. Available from: https://biologicalvariation.eu/ [Accessed Nov 2022].Search in Google Scholar

21. Miller, WG, Myers, GL. Commutability still matters. Clin Chem 2013;59:1291–3. https://doi.org/10.1373/clinchem.2013.208785.Search in Google Scholar PubMed

22. Miller, WG, Myers, GL, Rej, R. Why commutability matters. Clin Chem 2006;52:553–4. https://doi.org/10.1373/clinchem.2005.063511.Search in Google Scholar PubMed

23. Xiao, YL, Zhang, CB, Zhao, HJ, Kang, FF, Wang, W, Zhong, K, et al.. Application of ISO 13528 robust statistical method for external quality assessment of blood glucose measurements in China. Accred Qual Assur 2014;19:397–401. https://doi.org/10.1007/s00769-014-1078-z.Search in Google Scholar

24. Zhang, K, Lin, G, Wang, L, Sun, Y, Zhang, R, Xie, J, et al.. Harmonization of results has not been fully achieved for serum immunoglobulin measurements. Clin Chem Lab Med 2015;53:e309–e12. https://doi.org/10.1515/cclm-2015-0145.Search in Google Scholar PubMed

25. Stepman, HC, Tiikkainen, U, Stöckl, D, Vesper, HW, Edwards, SH, Laitinen, H, et al.. Measurements for 8 common analytes in native sera identify inadequate standardization among 6 routine laboratory assays. Clin Chem 2014;60:855–63. https://doi.org/10.1373/clinchem.2013.220376.Search in Google Scholar PubMed PubMed Central

Received: 2022-12-21
Accepted: 2023-02-03
Published Online: 2023-03-06
Published in Print: 2023-07-26

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2022-1299
Keywords for this article
cystatin C; external quality assessment; imprecision; peer group evaluation

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Addressing standardized definitions of post-COVID and long-COVID
  4. Reviews
  5. The chitinases as biomarkers in immune-mediate diseases
  6. Pitfalls in the diagnosis of hematuria
  7. Opinion Papers
  8. Remote decentralized clinical trials: a new opportunity for laboratory medicine
  9. Striving for a pragmatic contribution of biomarkers results to lifelong health care
  10. IFCC Paper
  11. External quality assessment practices in medical laboratories: an IFCC global survey of member societies
  12. Guidelines and Recommendations
  13. Antibody-mediated interferences affecting cardiac troponin assays: recommendations from the IFCC Committee on Clinical Applications of Cardiac Biomarkers
  14. General Clinical Chemistry and Laboratory Medicine
  15. Evaluation of four automated clinical analyzers for the determination of total 25(OH)D in comparison to a certified LC-MS/MS
  16. Standard −20 °C freezer storage protocols may cause substantial plasma renin cryoactivation
  17. Lower accuracy of testosterone, cortisol, and free T4 measurements using automated immunoassays in people undergoing hemodialysis
  18. Multicenter study to compare the diagnostic performance of CLIA vs. FEIA transglutaminase IgA assays for the diagnosis of celiac disease
  19. Imprecision remains to be improved in the measurement of serum cystatin C with heterogeneous systems
  20. Analytical validation of the modified Westergren method on the automated erythrocyte sedimentation rate analyzer CUBE 30 touch
  21. Reference Values and Biological Variations
  22. Systematic review and meta-analysis of within-subject and between-subject biological variation data of coagulation and fibrinolytic measurands
  23. Biological variation estimates for spot urine analytes and analyte/creatinine ratios in 33 healthy subjects
  24. Short-term biological variation of plasma uracil in a Caucasian healthy population
  25. Cardiovascular Diseases
  26. Elevated Hemolysis Index is associated with higher risk of cardiovascular diseases
  27. Infectious Diseases
  28. Clinical assessment of SNIBE Maglumi SARS-CoV-2 antigen fully-automated chemiluminescent immunoassay
  29. Pre-analytical considerations in the development of a prototype SARS-CoV-2 antigen ARCHITECT automated immunoassay
  30. SARS CoV-2 spike protein-guided exosome isolation facilitates detection of potential miRNA biomarkers in COVID-19 infections
  31. Monocyte distribution width alterations and cytokine storm are modulated by circulating histones
  32. Letters to the Editor
  33. Letter to the Editor regarding the article by Wayne J. Dimech et al. Time to address quality control processes applied to antibody testing for infectious diseases. Clin Chem Lab Med 2023; 61(2):205–212
  34. Response to Tony Badrick regarding “Letter to the Editor regarding the article by Wayne J. Dimech et al. Time to address quality control processes applied to antibody testing for infectious diseases. Clin Chem Lab Med 2023; 61(2):205–212 by”
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  37. Test results comparison: is the S-Monovette® Lithium-Heparin Gel+ a suitable replacement for the S-Monovette® Lithium-Heparin Gel on Alinity Abbott®?
  38. Analytical performance of Abbott’s ARCHITECT and Alinity TSH-receptor antibody (TRAb) assays
  39. Cis-AB showing discrepant results across different automated and manual methods: a case report and review of the literature
  40. A graphical tool to investigate method validation
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  44. 9th Annual Meeting of the Austrian Society for Laboratory Medicine and Clinical Chemistry (ÖGLMKC)
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