Bone Marrow Research raised questions about why PE is ineﬀective. The most important reason probably relates to the short duration of the treatment, which results in removal of FLC from the intravascular space only. As 85% of the total FLC load is in the extravascular compartment, this leads to rapid redistribution following PE of FLC into the intravascular compartment [58]. As a consequence, PE has a limited impact on the overall exposure of the kidneys to FLC. One obvious way to address is to utilise an extended treatment that removes FLC over a prolonged period of time and therefore removes FLCs that are undergoing redistribution from the extravascular to the intravascular compartment; the recent introduction of protein permeable dialysers into clinical practice has led to the practical assessment of the utility of extended extracorporeal removal of FLC in MM and AKI. 6. High Cut-Off (HCO) Haemodialysis Recently, clinical researchers have utilised a newer type of larger pore dialysis membrane (the Gambro HCO 1100, ini- tially developed for cytokine removal in critically ill patients on intensive care units by continuous dialysis modalities) and showed high clearances of both isotypes of FLC both in vitro and in vivo [59]. This ﬁnding was consistent with the physical characteristics of the dialyser, which has an eﬀective cut-oﬀ for the removal of molecules of a molecular weight of <50 Kd. In the initial report, the eﬃcacy of the dialyser was reinforced by signiﬁcant reductions in serum FLC levels in patients with MM and renal failure on extended dialysis sessions [59]. This work was followed by a pilot study of HCO dialysis in MM. Nineteen patients with biopsy proven cast nephropathy and severe AKI requiring dialysis were enrolled, treated with chemotherapy regimens that included novel agents, and prescribed extended HCO dialysis sessions of up to 8 hours a day [27]. The treatment was well tolerated, and recovery of renal function to independence of dialysis was seen in 14 patients (74% renal recovery). Of particular interest in this study was the observation that there was an early and sustained reduction of sFLC levels in those patients who recovered kidney function; those patients who had early interruptions in chemotherapy did not have early reductions in FLC levels and usually did not recover independent kidney function [27]. These initial results have led to the development of EuLITE, a randomised controlled trial of HCO dialysis versus conventional dialysis in patients with de novo MM, biopsy proven cast nephropathy, and dialysis-dependent acute kid- ney injury at presentation. 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