Free light chain ratio in patients with chronic renal failure
Authors:
P. Kušnierová 1,2; D. Zeman 1,2; O. Michnová 1; F. Všianský 1; D. Stejskal 1,2; V. Bartoš 1,2; T. Jelínek 3; R. Hájek 3
Authors‘ workplace:
Ústav laboratorní diagnostiky, Oddělení klinické biochemie, Fakultní nemocnice Ostrava
1; Katedra biomedicínských oborů, Lékařská fakulta, Ostravská univerzita
2; Hematoonkologická klinika, Fakultní nemocnice Ostrava
3
Published in:
Klin. Biochem. Metab., 28, 2020, No. 4, p. 144-149
Overview
Objective: Patients with chronic kidney disease (CKD) often show an increased serum free light chains concentration (FLC) accompanied by changes in the representation of both forms, i.e., kappa and lambda chains, and consequently by changing their ratio (FLC ratio). The aim of this study was to verify the reference limits of this ratio in patients with chronic renal failure, determined by commercial IVD of Binding Site.
Design: Methodological study.
Settings: Institute of Laboratory Diagnostics, Department of Clinical Biochemistry, University Hospital Ostrava.
Material and methods: The study included 150 patients with CKD and 17 controls. The concentration of creatinine, FLC kappa, FLC lambda was determined, the estimate of glomerular filtration according to CKD-EPI and serum FLC ratio were calculated according to the KDIGO classification, divided into groups G2 to G5. To exclude the presence of monoclonal FLC, serum protein electrophoresis, immunofixation electrophoresis and isoelectric focusing in agarose gel followed by affinity immunoblotting with antibodies against free kappa and lambda light chains (IEF / AIB) were used. Excel, MedCalc and Project R software were used for statistical data processing.
Results: Statistically significant differences were observed between concentrations of FLC kappa, FLC lambda and FLC ratio in individual groups (P < 0.0001). These parameters also statistically significantly correlated with creatinine concentration and with the estimate of glomerular filtration according to CKD EPI (P < 0.0001). In accordance with CLSI guideline EP28-A3C, the following reference limits were established for the FLC ratio in patients with CKD: a lower limit of 1.01 and an upper limit of 3.65.
Conclusion: Practical application of reference limits for the FLC ratio may increase the specificity of the FLC test for the detection of monoclonal FLC production in patients with CKD. The limits in this study were estimated using Binding Site diagnostics and may not be the same for other diagnostics.
Keywords:
Free light chains of immunoglobulins – immunoturbidimetry – Creatinine – enzymatic determination – estimation of glomerular filtration – reference limit – CKD
Sources
1. Waldmann, T. A., Strober, W., Mogielnicki, R. P. The renal handling of low molecular weight proteins. II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia. J. Clin. Invest., 1972, 51/8, p. 2162–2174.
2. Bradwell, A. R. Biology of immunoglobins. In: Serum Free Light Chain Analysis plus Hevylite, 7th Ed., edited by. Bradwell A. R., Birmingham, The Binding Site Ltd., 2015, p. 16–29, ISBN 978-0-9932196-0-3.
3. Maack, T., Johnson, V., Kau, S. T., Figueiredo, J., Sigulem, D. Renal filtration, transport, and metabolism of low-molecular-weight proteins: a review. Kidney Int., 1979, 16/3, p. 251–270.
4. Tichý, M, Vávrová, J, Friedecký, B, Maisnar, V. Přehled metod na stanovení volných lehkých řetězců. Klin. Biochem. Metab., 2008, 16/37, p. 93–96.
5. Solomon, A. Light chains of human immunoglobulins. Methods Enzymol., 1985, 116, p. 101–121.
6. Granátová, J, Bolková, M, Fantová, L, Hornová, L, Mašková, Z, Horák, J, Lánská, V. Volné lehké řetězce imunoglobulinů u nemocných v renální insuficienci. Klin. Biochem. Metab., 2008, 16/37, p. 106–110.
7. Hutchison, C. A., Harding, S., Hewins, P., Mead, G. P., Townsend, J., Bradwell, A. R., Cockwell, P. Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease. Clin. J. Am. Soc. Nephrol., 2008, 3/6, p. 1684-1690.
8. Hutchison, C. A., Basnayake, K., Cockwell, P. Serum free light chain assessment in monoclonal gammopathy and kidney disease. Nat. Rev. Nephrol., 2009, 5, p. 621-628.
9. Zima, T., Teplan, V., Tesař, V., Racek, J., Schück, O., Janda, J., Friedecký, B., Kubíček, Z., Kratochvíla, J. Doporučení České nefrologické společnosti a České společnosti klinické biochemie ČLS JEP k vyšetřování glomerulární filtrace. Klin. Biochem. Metab., 2009, 17/37, p. 109-117.
10. Zeman, D., Kušnierová, P., Švagera, Z., Všianský, F., Byrtusová, M., Hradílek, P., Kurková, B., Zapletalová, O., Bartoš, V. Assessment of Intrathecal Free Light Chain Synthesis: Comparison of Different Quantitative Methods with the Detection of Oligoclonal Free Light Chains by Isoelectric Focusing and Affinity-Mediated Immunoblotting. PLoS One., 2016, 15,11/11:e0166556. doi: 10.1371/journal.pone.0166556.
11. Viklický, O. Nová klasifikace chronických onemocnění ledvin. Postgrad. Nefrol., 2013, 11/1.
12. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. J Int. Soc. Nephrol., 2013, 3/1.
13. Clinical and Laboratory Standards Institute (CLSI). EP28-A3c Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline-third edition. Clin. Lab. Stand. Inst., 2010
14. Pavlov, I. Y., Wilson, A. R., Delgado, J. C. Resampling approach for determination of the method for re-ference interval calculation in clinical laboratory practice. Clin. Vaccine. Imunol., 2010, 17, p. 1217-1222.
15. Katzmann, J. A., Clark, R. J., Abraham, R. S., Bryant, S., Lymp, J. F., Bradwell, A. R., Kyle, R. A. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: Relative sensitivity for detection of monoclonal light chains. Clin. Chem., 2002, 48, p. 1437–1444.
16. Hájek, R. (ed.) et al.: Doporučení vypracované Českou myelomovou skupinou, Myelomovou sekcí České hematologické společnosti a Slovenskou Myelómovou Spoločností pro diagnostiku a léčbu mnohočetného myelomu. Transfuze. Hematol. dnes, 2018, 24/1, p. 2-157.
17. Nakano, T., Miyazaki, S., Takahashi, H. Immunochemical quantification of free immunoglobulin light chains from an analytical perspective. Clin. Chem. Lab. Med., 2006, 44/5, p. 522-532.
18. Vávrová, J., Kušnierová, P., Maisnar, V., Šolcová, L. Doporučení České společnosti klinické biochemie a České myelomové společnosti k laboratorní diagnostice monoklonálních gamapatií. Klin. Biochem. Metab., 2020, 28/49, p. 26-34.
19. Friedecký, B. Validní referenční intervaly a rozhodovací limity zcela závisí na úrovni harmonizace výsledků laboratorních měření. Klin. Biochem. Metab., 2014, 22/43, p. 114-115.
20. Nowrousian, M. R., Brandhorst, D., Sammet, C., Kellert, M., Daniels, R., Schuett, P., Poser, M., Mueller, S., Ebeling, P., Welt, A., Bradwell, A. R., Buttkereit, U., Opalka, B., Flasshove, M., Moritz, T., Seeber, S. Serum free light chain analysis and urine immunofixation electrophoresis in patients with multiple myeloma. Clin. Can. Res., 2005, 11, p. 8706–8714.
21. Rindlisbacher, B., Schild, Ch., Egger, F., Bacher, V. U., Pabst, T., Leichtle, A., Andres, M., Sédille-Mostafaie, N. Serum Free Light Chain Assay: Shift Toward a Higher κ/λ Ratio. J Appl. Lab. Med., 2020, 5/1, p. 114–125.
22. Caponi, L., Koni, E., Romiti, N., Paolicchi, A., Franzini, M. Different immunoreactivity of monomers and dimers makes automated free light chains assays not equivalent. Clin. Chem. Lab Med., 2018, 57/2, p. 221-229.
23. Tate, J. R., Hawley, C., Mollee, P. Response to article by Caponi et al. about serum free light chains. Clin. Chem. Lab. Med., 2018, 57/2, p. 1-2.
24. Kaplan, B., Aizenbud, B. M., Golderman, S., Yaskariev, R., Sela, B. A. Free light chain monomers in the diagnosis of multiple sclerosis. J. Neuroimmunol., 2010, 229/1-2, p. 263-271.
25. Kaplan, B., Livneh, A., Sela, B. A. Immunoglobulin free light chain dimers in human diseases. Sci. World J, 2011, 22/11, p. 726-735.
26. Kaplan, B., Golderman, S., Yahalom, G., Yaskariev, R., Ziv, T., Aizenbud, B. M., Sela, B. A., Livneh, A. Free light chain monomer-dimer patterns in the diagnosis of multiple sclerosis. J. Immunol. Methods., 2013, 390/1-2, p. 74-80.
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