Effects of Extracorporeal Blood Flow Rates on Patient Tolerance for LIXELLE® Treatment during Outpatient Hemodialysis.

INTRODUCTION: Accumulation of ß2-microglobulin (B2M) in dialysis patients contributes to several comorbidities of end-stage kidney disease (ESKD). The LIXELLE® device adsorbs B2M from blood using sorbent bead technology. Studies in Japan showed that LIXELLE treatment during hemodialysis (HD) at blood flow rates up to 250 mL/min removes B2M above HD alone and is well tolerated. We investigated tolerance for LIXELLE treatment during HD at higher HD blood flow rates standard in the USA. METHODS: A prospective, open-label, non-randomized, single-arm, early-feasibility study (EFS) assessed tolerance and safety of LIXELLE treatment during HD at blood flow rates up to 450 mL/min. ESKD patients (40-75 years old) on thrice weekly outpatient HD were eligible. After a 1-week HD run-in, patients received LIXELLE plus HD at a blood flow rate of 250 mL/min (1 week), followed by LIXELLE plus HD at a blood flow rate up to 450 mL/min (1 week). These blood flow rates were tested with three LIXELLE column sizes in sequence (treatment = 6 weeks). B2M removal was assessed for each combination. RESULTS: Ten patients with a historic intradialytic hypotension (IDH) rate of 0.42 events/HD session/patient were enrolled. Nine patients completed all combinations without IDH events (treatment IDH rate: 0.56 events/HD session/patient). No treatment-emergent serious adverse events or significant changes in red blood cell, platelet, or complement indices except haptoglobin were reported. B2M reduction ratios and removal of select proteins (<40 kDa) increased with escalating column size and blood flow rate. CONCLUSION: LIXELLE plus HD across all column sizes was safe and well tolerated at blood flow rates up to 450 mL/min. Extent of B2M removal corresponded to column size-blood flow rate combinations. This EFS provides a risk profile to guide further studies of LIXELLE in ESKD patients at US-standard blood flow rates.

Effect of beta(2)-microglobulin adsorption column on dialysis-related amyloidosis.

BACKGROUND: beta2-microglobulin (beta2-m) is considered a major pathogenic factor in dialysis-related amyloidosis (DRA), often seen in long-term dialysis patients. No effective therapy for this severely debilitating disease is currently available. Lixelle, an adsorption column, has been developed for the elimination of beta2-m; the efficacy of this column has been evaluated in this study. METHODS: Seventeen hemodialysis patients with DRA were first treated with high-flux dialysis for a minimum of 1 year. This was followed by 1-year treatment with Lixelle column connected in series to the high-flux dialyzer. Treatments were used three times a week for both phases of this study. During the study period, beta2-m, pinch strength, motor terminal latency, and activities of daily living were evaluated. RESULTS: After 1-year treatment with high-flux dialysis the beta2-m level remained unchanged; however, after 1-year treatment with the addition of the Lixelle column, beta2-m level decreased significantly from 34.5 +/- 8.4 mg/L to 28.8 +/- 7.3 mg/L (P < 0.05). After 1 year of Lixelle column use, the pinch strength increased from 6.8 +/- 4.7 pounds to 9.1 +/- 5.5 pounds (P < 0.01), and the median motor terminal latency was significantly reduced from 5.1 +/- 1.0 mseconds to 4.5 +/- 1.1 mseconds. A significant improvement was also observed in the activities of daily living score of the upper extremities. CONCLUSION: These results suggest that the addition of Lixelle to the high-flux dialyzer is associated with a significant clinical improvement in DRA patients.