BACKGROUND: High Cut-Off (HCO) dialysis membranes efficiently reduce serum free light chain (FLC) concentrations and may improve renal recovery and survival from multiple myeloma (MM) associated renal failure with cast nephropathy. However, clinical trials comparing dialysis with HCO versus conventional filters are lacking. The aim of this study was to assess clinical outcomes and economic impact of HCO dialyzers compared to conventional hemodialysis membranes in cast nephropathy. METHODS: Multicenter retrospective analysis of 19 patients treated for renal failure from FLC associated cast nephropathy with standard induction chemotherapy (bortezomib/dexamethasone). We compared hemodialysis treatment with High Cut-Off (n = 12) versus conventional dialyzers (n = 7). Primary endpoint was survival; secondary endpoints were renal recovery, renal function and treatment costs. RESULTS: At 12 months, patient survival was 25% in the HCO group versus 0% in controls (p = NS). A tendency towards faster renal recovery (p = 0.066) and better renal function at 3, 6 and 12 months (p = 0.109) after diagnosis of MM was noted in the HCO group. Complete renal response rate was achieved in 10.5 and 0% of HCO and control patients, respectively, partial renal response in 15.8 and 5.3%, and minor renal response in 26.3 and 15.8%, respectively. Both patient survival and renal recovery were significantly correlated with the extent of free light chain (FLC) reduction in serum. Median treatment costs were CHF 230'000 and 223'000 (p = NS) in the HCO and control group, respectively. CONCLUSIONS: Hemodialysis treatment with HCO membranes for cast nephropathy tended towards better survival as well as faster and better recovery of renal function versus conventional dialyzers. Moreover, total medical costs were comparable between groups. In the absence of results from randomized prospective trials on this topic, the use of HCO dialyzers in patients with renal failure from cast nephropathy may be recommended. Prospective randomized trials are required.