Plasma free light chains across chronic kidney disease stages: real-world patterns of kappa, lambda, and κ/λ ratio

Abstract Objectives Free immunoglobulin light chains (FLCs) are key biomarkers for plasma cell disorders, but interpretation is complicated in patients with impaired kidney function because reduced renal clearance leads to accumulation of polyclonal FLCs. Although FLC concentrations are known to increase as kidney function declines, data from routine clinical practice remain limited. Methods This retrospective study included 7,921 plasma samples referred for clinical FLC testing between 2021 and 2025 using the Siemens N Latex FLC assay. Free κ and λ concentrations were paired with same-day creatinine measurements, and estimated glomerular filtration rate (eGFR) was calculated. Samples were grouped according to KDIGO eGFR categories. To reduce the influence of overt monoclonal gammopathies, samples with extreme κ/λ ratios (<0.1 or >10) or a documented M-component were excluded. FLC distributions were estimated using non-parametric and bootstrap methods. Analyses were descriptive and performed at the sample level. Results Both κ and λ FLC concentrations increased progressively with declining eGFR. Across eGFR categories, κ concentrations increased approximately ten-fold and λ concentrations approximately five-fold from the highest to the lowest kidney function group. The κ/λ ratio remained relatively stable overall, although variability increased and upper percentiles widened at the lowest eGFR levels. Conclusions FLC concentrations are strongly influenced by kidney function, underscoring the importance of interpreting results in the context of eGFR. These real-world findings provide a descriptive overview of FLC distributions across kidney function categories. However, because of the retrospective design, repeated sampling, limited clinical information, and lack of diagnostic validation, the results should be considered exploratory.