Association between free light chain levels, and disease progression and mortality in chronic kidney disease

Lucie Desjardins, Sophie Liabeuf, Aurélie Lenglet, Horst-Dieter Lemke, Raymond Vanholder, Gabriel Choukroun, Ziad A Massy, European Uremic Toxin (EUTox) Work Group, Lucie Desjardins, Sophie Liabeuf, Aurélie Lenglet, Horst-Dieter Lemke, Raymond Vanholder, Gabriel Choukroun, Ziad A Massy, European Uremic Toxin (EUTox) Work Group

Abstract

Immunoglobulin free light chains (FLCs) form part of the middle molecule group of uremic toxins. Accumulation of FLCs has been observed in patients with chronic kidney disease (CKD). The aim of the present study was to measure FLC levels in patients at different CKD stages and to assess putative associations between FLC levels on one hand and biochemical/clinical parameters and mortality on the other. One hundred and forty patients at CKD stages 2-5D were included in the present study. Routine clinical biochemistry assays and assays for FLC kappa (κ) and lambda (λ) and other uremic toxins were performed. Vascular calcification was evaluated using radiological techniques. The enrolled patients were prospectively monitored for mortality. Free light chain κ and λ levels were found to be elevated in CKD patients (especially in those on hemodialysis). Furthermore, FLC κ and λ levels were positively correlated with inflammation, aortic calcification and the levels of various uremic toxins levels. A multivariate linear regression analysis indicated that FLC κ and λ levels were independently associated with CKD stages and β2 microglobulin levels. Elevated FLC κ and λ levels appeared to be associated with mortality. However, this association disappeared after adjustment for a propensity score including age, CKD stage and aortic calcification. In conclusion, our results indicate that FLC κ and λ levels are elevated in CKD patients and are associated with inflammation, vascular calcification and levels of other uremic toxins. The observed link between elevated FLC levels and mortality appears to depend on other well-known factors.

Figures

Figure 1
Figure 1
Levels of free light chain κ (A), λ (B) and κ/λ (C) as a function of the chronic kidney disease (CKD) stage. *p < 0.05 vs. healthy volunteers (HVs); $ p < 0.05 vs. CKD stage 2; £ < 0.05 vs. CKD stage 3; § p < 0.05 vs. CKD stage 4; ¤ p < 0.05 vs. CKD stage 5. CKD: chronic kidney disease. The dotted lines indicate the reference value derived from HVs (11.3 mg/L for FLC κ and 12.6 mg/L for FLC λ).
Figure 2
Figure 2
Kaplan–Meyer estimates of overall mortality for patients as a function of the median free light chain κ (A) and λ (B) levels.

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