Immunoglobulin Free Light Chains, Serum (LAB5774)

The serum free light chain ratio (sFLC ratio) may be mildly elevated in patients with impaired renal function.

Clinical Background

The sFLC assay measures the concentration of serum free kappa and lambda immunoglobulin light chains, and is used for the screening, prognostication, and monitoring of patients with plasma cell disorders (PCD). Interpretation of the assay is based on the ratio of free kappa to lambda light chains (sFLC ratio)1.

sFLCs are primarily cleared renally. It has been demonstrated that renal impairment can lead to an increased sFLC ratio, falsely raising concern for the presence of a kappa-restricted PCD2.

A recent large study screened participants without evidence of monoclonal gammopathy and proposed the following renal-specific reference intervals3:

eGFR (mL/min/1.73m2)sFLC Ratio
≥ 600.26-1.65
45-590.46-2.62
30-440.48-3.38
<300.54-3.30
Table 1: Renal clearance-specific reference intervals for free light chain ratio from Long et al., 2022.
Common Pitfalls
  • A mildly elevated sFLC-ratio in the setting of renal impairment often triggers concern for a plasma cell disorder.
Key Takeaways
  • A mildly elevated sFLC ratio in the setting of renal impairment may be due to decreased renal clearance and not a plasma cell disorder.
References
  1. Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, 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 Feb;23(2):215-24. doi: 10.1038/leu.2008.307. Epub 2008 Nov 20.
  2. Hutchison CA, Harding S, Hewins P, Mead GP, Townsend J, Bradwell AR, Cockwell P. Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2008 Nov;3(6):1684-90.
  3. Long TE, Indridason OS, Palsson R. et al. Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study. Blood Cancer J. 12, 133 (2022).

Written by: Vahid Azimi, MD

Reviewed by: Ann Gronowski, PhD

Last Edited: 2024-01-18

Last Reviewed: 2024-01-18