In a study published last year, they used structural equation modeling to evaluate the direct influence of GFR on serum κ-FLC concentration and the albumin quotient, and via these two variables the indirect influence on CSF κ-FLC concentration (Schmidauer M, et al. Clin Chem Lab Med. 2025;63[9]:1792–1799).
They were able to prove their hypothesis, Dr. Hegen said, and “this explains why there is no association between renal function and the κ-FLC index. Because the effect of impaired renal function on serum kappa free light chain is passed on to the CSF compartment, and by calculating the ratio of CSF and serum, the effect is partialed out. So we can integrate the kappa free light chain index independent of renal function.”
Studies of renal function and CSF κ-FLC involved patients with chronic renal failure, he noted in response to a question, not acute renal failure.
Asked how monoclonal interference might affect the method, Dr. Hegen said it’s largely unknown and a false-negative κ-FLC index is possible.
Dr. Hegen delved into the κ-FLC index versus absolute CSF κ-FLC concentration and why the index should be used.
He and coauthors measured κ-FLC in CSF and serum sample pairs of patients with CIS (n=60), MS (n=60), and other neurological diseases (n=60) from four MS centers (Presslauer S, et al. Mult Scler. 2016;22[4]:502–510). The κ-FLC intrathecal fraction, which is the proportion of intrathecally produced κ-FLC with regard to the whole amount of κ-FLC in CSF, was significantly higher in patients with MS (92.9 percent) and CIS (85.8 percent) than in patients with other neurological diseases (zero percent in 57 of 60 patients).
“For MS patients, 93 percent of the total kappa free light chain concentration is intrathecally produced, or [put] the other way around: Seven percent of the κ-FLC in the CSF stem from the blood compartment,” Dr. Hegen said. This decreases when looking at other diseases, especially in noninflammatory controls, where the contribution of serum κ-FLC is 100 percent to the CSF compartment. “This is important and why we should use the kappa free light chain index.”
Dr. Hegen used two patient examples to illustrate the importance of serum κ-FLC and the albumin quotient. Patient No. 1 has an absolute concentration of κ-FLC in CSF of 1 mg/L, with a serum κ-FLC concentration of 10.3 and an albumin quotient of 8.2, which results in a κ-FLC index of 11.84.
Patient No. 2 also has a concentration of κ-FLC in CSF of 1 mg/L but a higher serum κ-FLC concentration (22.6) and albumin quotient (13), which results in a κ-FLC index of 3.44.
Patient No. 1’s κ-FLC index of nearly 12 is positive and corresponds with oligoclonal bands, Dr. Hegen said, and patient No. 2’s κ-FLC index of 3.44 is negative, also confirmed by OCB.
“These two examples show we get further information by including the serum kappa free light chains as well as the blood CSF barrier function,” he said, which is important when it comes to neuromyelitis optica spectrum disease or myelin oligodendrocyte glycoprotein antibody-associated disease. “These two differential diagnoses have in a certain proportion of patients elevated albumin quotient, and therefore it’s important to consider” (Jarius S, et al. J Neurol Sci. 2011;306[1–2]:82–90; Jarius S, et al. J Neuroinflammation. 2020;17[1]:262).
In another study, Dr. Hegen and coauthors compared the diagnostic performance of CSF FLC concentration, FLC quotient, FLC index, and FLC intrathecal fraction in patients with CIS and MS and other neurological diseases (Hegen H, et al. Clin Chem Lab Med. 2019;57[10]:1574–1586).