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.