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Licensed Unlicensed Requires Authentication Published by De Gruyter November 9, 2021

High-resolution capillary electrophoresis for the determination of carbamylated albumin

  • Julien Favresse ORCID logo EMAIL logo and Joris Delanghe ORCID logo

Abstract

Objectives

Carbamylation is a non-enzymatic post-translational reaction of a primary amino group of a protein with isocyanate. The albumin carbamylation is a negative prognostic factor in chronic kidney disease (CKD) patients and induce charge difference implying an observed shift in electrophoretic mobility that can be measured through a symmetry factor (SF).

Methods

The Helena V8 and the Sebia Capillarys 2 systems were used for all experiments. The effect of in vitro carbamylation on the SF by spiking increasing concentrations of potassium isocyanate (KCNO) in serum of three healthy volunteers was investigated. Theoretical plate numbers (N) as a surrogate of separation efficiency were also calculated and correlations between SF and renal function biomarkers were performed on 284 patients.

Results

A dose-dependent impact of KCNO on the SF was observed for both methods with the Helena V8 being more sensitive. The mean N was significantly higher on the Helena V8 as compared to the Sebia Capillarys 2 (2,972 vs. 444.1, p<0.0001). The SF correlated significantly with eGFR (r=0.50, p<0.0001), creatinine (r=−0.31, p<0.0001) and urea (r=−0.34, p<0.0001) on the Helena V8. On the Sebia Capillarys 2, a significant correlation was only observed with eGFR (r=0.17, p=0.004). A better discrimination between CKD stages was also observed using the Helena V8.

Conclusions

Thanks to a higher mean N, the Helena V8 might offer new possibilities, including detection of carbamylated albumin through SF calculation. Further studies are still needed to confirm the interest of using this type of assays in clinical routine.


Corresponding author: Julien Favresse, Department of Laboratory Medicine, Clinique St-Luc Bouge, 8 Rue Saint-Luc, 5000 Namur, Belgium; and Department of Pharmacy, Namur Research Institute for LIfes Sciences, University of Namur, Namur, Belgium, Phone: +32 81 20 91 44, E-mail:

Acknowledgments

The authors thanks Mr Thierry De Bruyne for performing the Adobe InDesign analysis and Mr Guillaume Sondag for performing the spiking experiment.

  1. Research funding: None declared.

  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 the three healthy volunteers included in this study.

  5. Ethical approval: The local Institutional Review Board approved the study exempt from review.

References

1. Kyle, R, Shampo, M. Arne Tiselius – father of electrophoresis. Mayo Clin Proc 2005;80:302.Search in Google Scholar

2. Hage, DS. An overview of CE in clinical analysis. Methods Mol Biol 2019;1972:3–11. https://doi.org/10.1007/978-1-4939-9213-3_1.Search in Google Scholar

3. Morrison, T, Booth, RA, Hauff, K, Berardi, P, Visram, A. Laboratory assessment of multiple myeloma. Adv Clin Chem 2019;89:1–58. https://doi.org/10.1016/bs.acc.2018.12.001.Search in Google Scholar

4. Slev, PR, Williams, BG, Harville, TO, Ashwood, ER, Bornhorst, JA. Efficacy of the detection of the alpha1-antitrypsin “Z” deficiency variant by routine serum protein electrophoresis. Am J Clin Pathol 2008;130:568–72. https://doi.org/10.1309/jwewe4qrqkj5ejeu.Search in Google Scholar

5. Tate, JR, Keren, DF, Mollee, P. A global call to arms for clinical laboratories – harmonised quantification and reporting of monoclonal proteins. Clin Biochem 2018;51:4–9. https://doi.org/10.1016/j.clinbiochem.2017.11.009.Search in Google Scholar

6. Petersen, JR, Okorodudu, AO, Mohammad, A, Payne, DA. Capillary electrophoresis and its application in the clinical laboratory. Clin Chim Acta 2003;330:1–30. https://doi.org/10.1016/s0009-8981(03)00006-8.Search in Google Scholar

7. Jabeen, R, Payne, D, Wiktorowicz, J, Mohammad, A, Petersen, J. Capillary electrophoresis and the clinical laboratory. Electrophoresis 2006;27:2413–38. https://doi.org/10.1002/elps.200500948.Search in Google Scholar PubMed

8. Plebani, M. New insights on the analytical performances for detecting and quantifying monoclonal proteins. Clin Chem Lab Med 2020;26:457–9. https://doi.org/10.1515/cclm-2019-1266.Search in Google Scholar PubMed

9. Favresse, J, Yolande, L, Gras, J. Evaluation of a capillary electrophoresis system for the separation of proteins. J Appl Lab Med 2021;6:1611–7. https://doi.org/10.1093/jalm/jfab044.Search in Google Scholar PubMed

10. Booth, RA, McCudden, CR, Balion, CM, Blasutig, IM, Bouhtiauy, I, Rodriguez-Capote, K, et al.. Candidate recommendations for protein electrophoresis reporting from the Canadian Society of Clinical Chemists Monoclonal Gammopathy Working Group. Clin Biochem 2018;51:10–20. https://doi.org/10.1016/j.clinbiochem.2017.10.013.Search in Google Scholar PubMed

11. Delanghe, S, Moerman, A, Pletinck, A, Schepers, E, Glorieux, G, Van Biesen, W, et al.. Quantification of carbamylated albumin in serum based on capillary electrophoresis. Electrophoresis 2017;38:2135–40. https://doi.org/10.1002/elps.201700068.Search in Google Scholar PubMed

12. Donato, LJ, Jenkins, SM, Smith, C, Katzmann, JA, Snyder, MR. Reference and interpretive ranges for alpha(1)-antitrypsin quantitation by phenotype in adult and pediatric populations. Am J Clin Pathol 2012;138:398–405. https://doi.org/10.1309/ajcpmeejk32acyfp.Search in Google Scholar PubMed

13. Chartier, C, Boularan, AM, Dupuy, AM, Badiou, S, Bargnoux, AS, Cognot, C, et al.. Evaluation of two automated capillary electrophoresis systems for human serum protein analysis. Clin Biochem 2011;44:1473–9. https://doi.org/10.1016/j.clinbiochem.2011.05.022.Search in Google Scholar PubMed

14. Regeniter, A, Siede, WH. Peaks and tails: evaluation of irregularities in capillary serum protein electrophoresis. Clin Biochem 2018;51:48–55. https://doi.org/10.1016/j.clinbiochem.2017.09.017.Search in Google Scholar PubMed

15. Delanghe, S, Delanghe, JR, Speeckaert, R, Van Biesen, W, Speeckaert, MM. Mechanisms and consequences of carbamoylation. Nat Rev Nephrol 2017;13:580–93. https://doi.org/10.1038/nrneph.2017.103.Search in Google Scholar PubMed

16. Berg, AH, Drechsler, C, Wenger, J, Buccafusca, R, Hod, T, Kalim, S, et al.. Carbamylation of serum albumin as a risk factor for mortality in patients with kidney failure. Sci Transl Med 2013;5:1–23. https://doi.org/10.1126/scitranslmed.3005218.Search in Google Scholar PubMed PubMed Central

17. Levey, AS, Stevens, LA, Schmid, CH, Zhang, YL, Castro, AF3rd, Feldman, HI, et al.. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;9:604–12. https://doi.org/10.7326/0003-4819-150-9-200905050-00006.Search in Google Scholar PubMed PubMed Central

18. Geffre, A, Concordet, D, Braun, JP, Trumel, C. Reference value advisor: a new freeware set of macroinstructions to calculate reference intervals with Microsoft Excel. Vet Clin Pathol 2011;40:107–12. https://doi.org/10.1111/j.1939-165x.2011.00287.x.Search in Google Scholar

19. CLSI Document C28-A3c:2008. Measurement procedure comparison and bias estimation using patient samples, approved guidelines, 3rd ed. Wayne (PA): CLSI; 2013, vol 30:1–80 pp.Search in Google Scholar


Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2021-0926).


Received: 2021-08-19
Accepted: 2021-10-28
Published Online: 2021-11-09
Published in Print: 2022-01-27

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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