A silicon nanopore membrane blood filter enabling anticoagulant free continuous renal replacement therapy for acute kidney injury

项目摘要 急性肾损伤(AKI)通常发生在ICU的危重病人中。严重急性心肌梗死患者经常 需要连续性肾脏替代疗法(CRRT)，因为它能够实现血流动力学的稳定性和更好的 音量控制。抗凝治疗经常被用来保持CRRT回路(尤其是血液过滤器) 由于许多危重患者是血栓前状态，和/或当CRRT通常用于 好几天。然而，全身肝素和局部柠檬酸抗凝治疗都与 更高的成本、更高的电路复杂性和复杂性。因此，我们建议开发一种 基于超高通量血液兼容硅的无凝血滤清器(血盒) 用于扩展体外应用的纳米孔膜(SNM)技术。血盒将会 在CRRT疗程的时间里，在几乎没有抗凝的情况下进行无血栓操作，以消除成本， 减少并发症，减少失血量，降低手术费用 由于滤器凝结和更换而导致的CRRT，并降低无法提供足够的透析剂剂量的风险 病危的AKI患者。在这项SBIR第二阶段提案中，我们将开发一种临床规模的血盒和 然后在工作台上和无肾猪身上评估尿毒症毒素清除和血液相容性 模特。

Project Summary Acute Kidney Injury (AKI) commonly occurs in critically ill patients in the ICU. Patients with severe AKI often require continuous renal replacement therapy (CRRT) because it enables hemodynamic stability and better volume control. Anticoagulation therapy is frequently used to keep the CRRT circuit (especially the blood filter) from clotting as many critically ill patients are prothrombotic, and/or when CRRT is commonly performed for multiple days. However, both systemic heparin and regional citrate anticoagulation therapy are associated with higher costs, increased circuit complexity, and complications. Consequently, we propose to develop an anticoagulant-free blood filter (the HemoCartridge) based on the ultra-high-flux and blood compatible silicon nanopore membrane (SNM) technology for extended extracorporeal applications. The HemoCartridge will operate clot free with little to no anticoagulation for the length of a CRRT session to eliminate the costs, complexity, and complications of administering anticoagulation therapy, reduce blood loss, reduce the cost of CRRT due to filter clotting and replacement, and reduce the risk of not delivering an adequate dialytic dose to the critically ill AKI patient. In this SBIR Phase II proposal, we will develop a clinical-scale HemoCartridge and then assess uremic toxin clearance and hemocompatibility on the bench top and in the anephric porcine model.