Lab Med Online.  2019 Jan;9(1):12-16. 10.3343/lmo.2019.9.1.12.

Increment of Serum Free Light Chain Kappa/Lambda Ratio in Patients with Renal Dysfunction

• Jung JW
• Cheong MA
• Kim HJ
• Kim SH
• Oh AC
• Lee JK
• Hong YJ
• Chang YH

• KMID: 2430204
• DOI: http://doi.org/10.3343/lmo.2019.9.1.12

Abstract

BACKGROUND
Since free light chain (FLC) is metabolized in the kidney, serum FLC concentration and kappa/lambda ratio are increased in patients with decreased renal function, even in the absence of monoclonal protein. In this study, we measured serum FLC levels to investigate the change in kappa/lambda ratios in relation to the severity of renal dysfunction.
METHODS
Serum FLC concentrations were measured in 92 archived serum samples from patients diagnosed with chronic kidney disease using the Freelite assay (The Binding Site Group Ltd., UK), and kappa/lambda ratios were calculated. Serum creatinine levels were assayed to calculate estimated glomerular filtration rate (eGFR), and patients were divided into subgroups according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines. We analyzed the difference in serum FLC levels and kappa/lambda ratios between subgroups.
RESULTS
Serum FLC levels and kappa/lambda ratios increased depending on the severity of renal dysfunction. When patients were classified by setting cut-off value of eGFR as 60 mL/min/1.73 m2 (group A: eGFR ≥60 mL/min/1.73 m2, group B: < 60 mL/min/1.73 m2), the kappa/lambda ratio of group B was significantly higher than that of group A (group B: 1.60±0.46 vs. group A: 1.35±0.27, P=0.018). Serum FLC kappa/lambda ratios were within the previously determined renal reference interval (0.37-3.1).
CONCLUSIONS
When interpreting results of serum FLC kappa/lambda ratio, renal function status should be considered in addition to hematological findings. If renal function deteriorates, a wider renal reference interval is preferred instead of the usual reference interval.

Keyword

Serum free light chain; Kappa/lambda ratio; Chronic kidney disease

MeSH Terms

Binding Sites
Creatinine
Glomerular Filtration Rate
Humans
Kidney
Kidney Diseases
Renal Insufficiency, Chronic
Creatinine

Figure

• 

  Fig. 1. Comparison of kappa/lambda ratio among patient groups according to severity of renal dysfunction. (A) Comparison between 4 groups divided by KDIGO guideline (group 2, mildly decreased; group 3, moderately decreased; group 4, severely decreased; group 5, kidney failure). (B) Comparison between two groups, group A (eGFR ≥60 mL/min/1.73 m2) vs. group B (eGFR <60 mL/min/1.73 m2). KDIGO represents Kidney Disease Improving Global Outcomes.

Reference

1.Bradwell AR., Carr-Smith HD., Mead GP., Harvey TC., Drayson MT. Serum test for assessment of patients with Bence Jones myeloma. Lancet. 2003. 361:489–91.

2.Bradwell AR. Serum free light chain measurements move to center stage. Clin Chem. 2005. 51:805–7.

3.Heher EC., Rennke HG., Laubach JP., Richardson PG. Kidney disease and multiple myeloma. Clin J Am Soc Nephrol. 2013. 8:2007–17.

4.Finkel KW., Cohen EP., Shirali A., Abudayyeh A. American Society of Nephrology Onco-Nephrology Forum. Paraprotein–related kidney disease: evaluation and treatment of myeloma cast nephropathy. Clin J Am Soc Nephrol. 2016. 11:2273–9.

5.Katzmann JA., Kyle RA., Benson J., Larson DR., Snyder MR., Lust JA., Rajkumar SV., Dispenzieri A. Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009. 55:1517–22.

6.Rajkumar SV., Dimopoulos MA., Palumbo A., Blade J., Merlini G., Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014. 15:e538–48.

7.Kumar S., Paiva B., Anderson KC., Durie B., Landgren O., Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016. 17:e328–46.

8.Nowrousian MR., Brandhorst D., Sammet C., Kellert M., Daniels R., Schuett P, et al. Serum free light chain analysis and urine immunofxation electrophoresis in patients with multiple myeloma. Clin Cancer Res. 2005. 11:8706–14.

9.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.Katzmann JA., Clark RJ., Abraham RS., Bryant S., Lymp JF., Bradwell AR, et al. 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. 48:1437–44.

11.Hutchison CA., Plant T., Drayson M., Cockwell P., Kountouri M., Basnay-ake K, et al. Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure. BMC Nephrol. 2008. 9:11.

12.Abadie JM., van Hoeven KH., Wells JM. Are renal reference intervals required when screening for plasma cell disorders with serum free light chains and serum protein electrophoresis? Am J Clin Pathol. 2009. 131:166–71.

13.Diamantidis MD., Ioannidou-Papagiannaki E., Ntaios G. Novel extended reference range for serum kappa/lambda free light chain ratio in diagnosing monoclonal gammopathies in renal insuffcient patients. Clin Biochem. 2009. 42:1202–3.

14.Park JW., Kim YK., Bae EH., Ma SK., Kim SW. Combined analysis using extended renal reference range of serum free light chain ratio and serum protein electrophoresis improves the diagnostic accuracy of multiple myeloma in renal insuffciency. Clin Biochem. 2012. 45:740–4.

15.Levey AS., Stevens LA., Schmid CH., Zhang YL., Castro AF 3rd., Feldman HI, et al. A new equation to estimate glomerular fltration rate. Ann Intern Med. 2009. 150:604–12.

16.Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013. 3:1–150.

17.Leung N., Barnidge DR., Hutchison CA. Laboratory testing in monoclonal gammopathy of renal signifcance (MGRS). Clin Chem Lab Med. 2016. 54:929–37.

18.Hutchison CA., Landgren O. Polyclonal immunoglobulin free light chains as a potential biomarker of immune stimulation and infamma-tion. Clin Chem. 2011. 57:1387–9.