Abstract
Background: Quantification of serum free light chains (FLC) is important in the diagnosis of plasma cell diseases where an abnormal kappa:lambda ratio infers a population of monoclonal plasma cells. The Freelite™ and N Latex assays have been validated in populations without kidney disease but there is a paucity of data relating to the use of these assays in end stage kidney disease (ESKD). The aim of the study was to compare FLC assay performance in ESKD patients on haemodialysis.
Methods: Cross-sectional multi-centre study comparing the performance of the two assays on 112 haemodialysis patients without known paraproteinaemia. We quantified FLC pre- and post-dialysis using both the N Latex and the Freelite assays.
Results: FLC levels were elevated by both assays. Lambda FLC levels were considerably higher by the N Latex assay. Using the proposed renal reference range for Freelite (0.37–3.1) all but one patient had normal kappa:lambda FLC ratios. In contrast, there were no abnormal FLC ratios pre-dialysis using the N Latex assay. This was due to lambda FLC reading significantly higher by the N Latex assay. Kappa and lambda FLC levels decreased with dialysis but remained elevated above the normal range. The excess of lambda FLC by N Latex persisted post-dialysis but was somewhat attenuated. Dialysis adequacy and dialysis modality predicted clearance of kappa and lambda FLC by both assays.
Conclusions: The N Latex assay reported significantly higher pre-dialysis lambda FLC concentrations compared with the Freelite assays. Clinicians should be aware of the need for a separate renal reference range for interpreting FLC ratio using the Freelite assay but not for the N Latex assay in ESKD patients.
Acknowledgments
We thank Siemens Healthcare Diagnostics for providing N Latex free light chain reagents.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: JT is a member of the editorial board of CCLM.
Honorarium: None declared.
Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Bradwell, AR, editor. Serum free light chain analysis, 5th ed. Birmingham: The Binding Site Ltd, 2008:167–73.Search in Google Scholar
2. Abraham RS, Katzmann JA, Clark RJ, Bradwell AR, Kyle RA, Gertz MA. Quantitative analysis of serum free light chains. A new marker for the diagnostic evaluation of primary systemic amyloidosis. Am J Clin Pathol 2003;119:274–8.10.1309/LYWM47K2L8XYFFB3Search in Google Scholar
3. Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001;97:2900–2.10.1182/blood.V97.9.2900Search in Google Scholar PubMed
4. Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, et al. International Myeloma Working Group. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009;23:215–24.10.1038/leu.2008.307Search in Google Scholar PubMed
5. Hoedemakers RM, Pruijt JF, Hol S, Teunissen E, Martens H, Stam P, et al. Clinical comparison of new monoclonal antibody-based nephelometric assays for free light chain kappa and lambda to polyclonal antibody-based assays and immunofixation electrophoresis. Clin Chem Lab Med 2011:50:489–95.10.1515/cclm.2011.793Search in Google Scholar PubMed
6. Hutchison CA, Plant T, Drayson M, Cockwell P, Kountouri M, Basnayake K, et al. Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure. BMC Nephrol 2008;9:11.10.1186/1471-2369-9-11Search in Google Scholar PubMed PubMed Central
7. Hutchison CA, Harding S, Hewins P, Mead GP, Townsend J, Bradwell AR, et al. Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease. Clin J Am Soc Nephrol 2008;3:1684–90.10.2215/CJN.02290508Search in Google Scholar PubMed PubMed Central
8. Jacobs JF, Hoedemakers RM, Teunissen E, Te Velthuis H. N Latex FLC serum free light-chain assays in patients with renal impairment. Clin Chem Lab Med 2014;52:853–9.10.1515/cclm-2013-0864Search in Google Scholar PubMed
9. Tate J, Bazeley S, Klinberg S, Pretorius CJ, Hawley C, Mollee P. Comparison of the Freelite and N Latex srum free light chain (FLC) assays in chronic kidney disease [abstract]. Clin Biochem Rev 2012;33:S41.Search in Google Scholar
10. Data from manufacturer’s dialyser data sheets. www.fmc-ag.com, www.nipro.com, www.baxter.com.Search in Google Scholar
11. Jenner W, Klingberg S, Tate JR, Wilgen U, Ungerer JP, Pretorius CJ. Combined light chain immunofixation to detect monoclonal gammopathy: a comparison to standard electrophoresis in serum and urine. Clin Chem Lab Med 2014;52:981–7.10.1515/cclm-2014-0023Search in Google Scholar PubMed
12. MedCalc for Windows v. 15.2.2 (2015). www.medcalc.org.Search in Google Scholar
13. Lavatelli F, Brambilla F, Valentini V, Rognoni P, Casarini S, Di Silvestre D, et al. A novel approach for the purification and proteomic analysis of pathogenic immunoglobulin free light chains from serum. Biochim Biophys Acta 2011;1814:409–19.10.1016/j.bbapap.2010.12.012Search in Google Scholar PubMed
14. Hutchison CA, Cockwell P, Reid S, Chandler K, Mead GP, Harrison J, et al. Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. Clin J Am Soc Nephrol 2007;18:886–95.10.1182/blood.V108.11.5112.5112Search in Google Scholar
15. Hutchison CA, Basnayake K, Cockwell P. Serum free light chain assessment in monoclonal gammopathy and kidney disease. Nat Rev Nephrol 2009;11:621–8.10.1038/nrneph.2009.151Search in Google Scholar PubMed
16. Berlanga O, Carr-Smith H, Harding S. Response to Jacobs: N Latex FLC serum free light-chain assays in patients with renal impairment. Clin Chem Lab Med 2014;52:e243–5.10.1515/cclm-2014-0420Search in Google Scholar PubMed
Supplemental Material:
The online version of this article (DOI: 10.1515/cclm-2015-0799) offers supplementary material, available to authorised users.
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