In this work we investigated the acute effects of hemodiafiltration with endogenous reinfusion (HFR therapy) on the removal of free immunoglobulin light chains (FIgLCs), which may be considered members of the family of uremic toxins. In two groups of patients – group 1 (polyclonal FIgLCs production) and group 2 (monoclonal plasma cell proliferative disorders), we analyzed the pre- and postdialysis levels of ĸ- and λ-chains. In group 1 we observed a significant reduction of FIgLCs (p < 0.01). A similar trend was found in patients of group 2 only for ĸ-chains. The FIgLCs removal ratio was significantly higher for ĸ- than λ-chains in the two patient groups. In vitro data showed affinity of macroporous resin to binding FIgLCs. Our results show that the HFR therapy could be effective in removing FIgLCs, particularly ĸ-chains in dialysis patients with polyclonal and monoclonal FIgLCs production.