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Review
. 2021 Nov 19:13:11795735211042166.
doi: 10.1177/11795735211042166. eCollection 2021.

The Influence of Renal Function Impairment on Kappa Free Light Chains in Cerebrospinal Fluid

Franz F Konen  1 , Philipp Schwenkenbecher  1 , Ulrich Wurster  1 , Konstantin F Jendretzky  1 , Nora Möhn  1 , Stefan Gingele  1 , Kurt-Wolfram Sühs  1 , Malte J Hannich  2 , Matthias Grothe  3 , Torsten Witte  4 , Martin Stangel  1 , Marie Süße  3 , Thomas Skripuletz  1
Affiliations
Review

The Influence of Renal Function Impairment on Kappa Free Light Chains in Cerebrospinal Fluid

Franz F Konen et al. J Cent Nerv Syst Dis. .

Abstract

Background: The determination of kappa free light chains (KFLC) in cerebrospinal fluid (CSF) is an upcoming biomarker for the detection of an intrathecal immunoglobulin synthesis. Since renal function impairment leads to altered serum KFLC and albumin concentrations, interpretation of KFLC in CSF may be influenced by these parameters.

Methods: In this two-center study, the influence of renal function (according to the CKD-EPI creatinine equation) on KFLC and albumin concentrations was investigated in patients with "physiological" (n = 139), "non-inflammatory" (n = 146), and "inflammatory" (n = 172) CSF profiles in respect to the KFLC index and the evaluation in quotient diagrams in reference to the hyperbolic reference range (KFLC IF).

Results: All sample groups displayed declining KFLC indices and KFLC IF values with decreasing renal function (P-values between <.0001 and .0209). In "inflammatory" CSF profile samples, 15% of the patients presented a KFLC index <5.9 while 10% showed an intrathecal KFLC fraction below QKappa(lim), suggesting possible false negative KFLC results.

Conclusions: The influence of renal function should be considered while interpreting KFLC results in patients with neuroinflammatory diseases. The interpretation of KFLC in quotient diagrams is less susceptible to renal function impairment than the KFLC index and should be preferentially used.

Keywords: biomarker; cerebrospinal fluid; eGFR; kappa free light chains (KFLC); reiber’s diagram; renal function.

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Conflict of interest statement

Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Correlation with renal function in “physiological” cerebrospinal fluid (CSF) profile patients. Depicted are the correlations of serum albumin (A1), cerebrospinal fluid (CSF) albumin (A2), serum kappa free light chain (KFLC) (B1), and CSF KFLC (B2) concentrations with renal function estimated by the glomerular filtration rate (eGFR) according to the CKD-EPI equation in “physiological” CSF profile patients. Further, the correlation between CSF/serum quotients of albumin (A3) and KFLC (B3) and eGFR are shown. In C1, the correlation between eGFR and KFLC index (QKFLC / QAlb) is depicted, while C2 presents the correlation between eGFR and the intrathecal KFLC fraction in relation to Qmean according to Reiber’s diagram for KFLC (KFLC IF). In the caption, P-values of linear regression and Spearman’s r (Gaussian distributed values) or Pearson’s r (nonparametric distributed values) as well as the coefficient of correlation (ρ) are shown.
Figure 2.
Figure 2.
Correlation with renal function in “non-inflammatory” cerebrospinal fluid (CSF) profile patients. Depicted are the correlations of serum albumin (A1), cerebrospinal fluid (CSF) albumin (A2), serum kappa free light chain (KFLC) (B1), and CSF KFLC (B2) concentrations with renal function estimated by the glomerular filtration rate (eGFR) according to the CKD-EPI equation in “non-inflammatory” CSF profile patients. Further, the correlation between CSF/serum quotients of albumin (A3) and KFLC (B3) and eGFR is shown. In C1, the correlation between eGFR and KFLC index (QKFLC/QAlb) is depicted, while C2 presents the correlation between eGFR and the intrathecal KFLC fraction in relation to Qmean according to Reiber’s diagram for KFLC (KFLC IF). In the caption, P-values of linear regression and Spearman’s r (Gaussian distributed values) or Pearson’s r (nonparametric distributed values) as well as the coefficient of correlation (ρ) are shown.
Figure 3.
Figure 3.
Correlation with renal function in “inflammatory” cerebrospinal fluid (CSF) profile patients. Depicted are the correlations of serum albumin (A1), cerebrospinal fluid (CSF) albumin (A2), serum kappa free light chain (KFLC) (B1), and CSF KFLC (B2) concentrations with renal function estimated by the glomerular filtration rate (eGFR) according to the CKD-EPI equation in “inflammatory” CSF profile patients. Further, the correlation between CSF/serum quotients of albumin (A3) and KFLC (B3) and eGFR is shown. In C1, the correlation between GFR and KFLC index (QKFLC/QAlb) is depicted, while C2 presents the correlation between eGFR and the intrathecal KFLC fraction in relation to Qmean according to Reiber’s diagram for KFLC (KFLC IF). In the caption, P-values of linear regression and Spearman’s r (Gaussian distributed values) or Pearson’s r (nonparametric distributed values) as well as the coefficient of correlation (ρ) are shown.
Figure 4.
Figure 4.
Kappa free light chain (KFLC) index and KFLC fraction in age- and renal function-matched samples. Depicted are comparisons of KFLC indices and intrathecal KFLC fractions in relation to Qmean according to Reiber’s diagram for KFLC (KFLC IF) in samples of “physiological” cerebrospinal fluid (CSF) profile and “non-inflammatory” CSF profile patients. Samples of patients with the most impaired renal function estimated by the glomerular filtration rate (eGFR) according to the CKD-EPI equation (n = 15) were age-matched with samples of patients with the highest possible eGFR (n = 15) (patients below the age of 60 years (A); patients above the age of 60 years (B)). Further, the samples of the oldest patients (n = 15) were eGFR-matched with the youngest possible patient samples (n = 15) (patients with reduced renal function (C); patients with normal renal function (D)). P-values are shown above the arrowed line.
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