We proposed a combination of convective and diffusive transport mechanisms as high cut-off (HCO) post-dilution hemodiafiltration dialysis technique to optimize serum immunoglobulin free light chains (FLCs) removal which may improve dialysis dependent renal failure in patients with multiple myeloma. To reduce bleeding risk regional citrate anticoagulation was successfully used for the first 7 h followed by 1 h anticoagulant-free hemodiafiltration to avoid citrate accumulation. We retrospectively assessed the effect of FLCs reduction on the renal outcome of 28 patients treated with 133 citrate extended post-dilution HCO (Theralite 2100; Gambro, Lund, Sweden) hemodiafiltration sessions between 2010 and 2016. Renal recovery was demonstrated in 61% of all patients. Twenty-three patients achieved more than 50% reduction of FLCs concentrations and 88% of those became dialysis independent. Our experience supports the extended citrate HCO hemodiafiltration as a good treatment strategy that enable a sustained reduction in serum FLCs concentration and recovery of renal function.