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.
Highlights
Uremic toxins are retention solutes that accumulate in the blood of patients with kidney failure.These molecules contribute to a variety of metabolic and functional disorders
Our present results show that free light chain (FLC) κ and λ levels are associated with levels of inflammatory markers (IL6 and C-reactive protein (CRP))
The present study of patients at various chronic kidney disease (CKD) stages confirmed that FLC κ and λ levels are positively correlated with declining kidney function
Summary
Uremic toxins are retention solutes that accumulate in the blood of patients with kidney failure. These molecules contribute to a variety of metabolic and functional disorders (e.g., impaired immune responses). Immunoglobulin light chains have a mean molecular weight of 25,000 Daltons for monomers and approximately 50,000 Daltons for dimers and are considered to be members of the middle molecule family of uremic toxins [1]. Light chains are synthesized by plasma cells; two light chains pair with two heavy chains to form the various classes of immunoglobulins [2]. Plasma cells normally produce slightly more light chains than heavy chains, and the excess light chains are either excreted or catabolized by the kidney [4]. It is thought that light chains (and FLCs) have a role in kidney disease
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