Supplementary Material for: Effects of extracorporeal blood flow rates on patient tolerance for LIXELLE® treatment during outpatient hemodialysis

Introduction: Accumulation of β2-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 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 United States (US).
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 one-week HD run-in, patients received LIXELLE plus HD at a blood flow rate of 250 mL/min (one week), followed by LIXELLE plus HD at a blood flow rate up to 450 mL/min (one week). These blood flow rates were tested with three LIXELLE column sizes in sequence (treatment = six 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.

引言：β2-微球蛋白（β2-microglobulin, B2M）在透析患者体内的蓄积会诱发多种终末期肾病（end stage kidney disease, ESKD）相关并发症。LIXELLE®装置通过吸附剂微球技术从血液中清除B2M。日本的既往研究显示，在血液透析（hemodialysis, HD）过程中采用LIXELLE®疗法，当血流速率最高达250 mL/min时，其对B2M的清除效果优于单纯血液透析，且耐受性良好。本研究旨在评估美国（US）临床标准的更高血流速率下，血液透析联合LIXELLE®疗法的耐受性。
方法：本研究为一项前瞻性、开放标签、非随机单臂早期可行性研究（early feasibility study, EFS），旨在评估血流速率最高达450 mL/min时，血液透析联合LIXELLE®疗法的耐受性与安全性。纳入标准为年龄40~75岁、接受每周三次门诊血液透析的ESKD患者。在为期1周的血液透析导入期后，患者先接受血流速率250 mL/min的LIXELLE®联合血液透析治疗（持续1周），随后接受血流速率最高达450 mL/min的LIXELLE®联合血液透析治疗（持续1周）。研究依次使用三种不同规格的LIXELLE®吸附柱完成上述血流速率测试，总治疗周期为6周。针对每种组合方案，均对B2M清除情况进行评估。
结果：本研究共纳入10例患者，其基线透析间期低血压（intradialytic hypotension, IDH）发生率为0.42次/每次血液透析治疗/患者。9例患者完成了全部方案的治疗，期间未发生透析间期低血压事件（治疗期间IDH发生率为0.56次/每次血液透析治疗/患者）。未报告治疗相关新发严重不良事件，除结合珠蛋白外，红细胞、血小板或补体指标均未出现显著变化。随着吸附柱规格提升与血流速率加快，B2M降低率与分子量<40 kDa的特定蛋白质清除率均有所升高。
结论：在血流速率最高达450 mL/min的情况下，所有规格吸附柱搭配的LIXELLE®联合血液透析疗法均具有良好的安全性与耐受性。B2M的清除效果与吸附柱规格-血流速率组合呈正相关。本早期可行性研究明确了相关风险特征，可为后续针对美国标准血流速率下ESKD患者使用LIXELLE®疗法的研究提供指导。