Abstract: TH-PO0860
In Vivo Assessment of Nafamostat as a Regional Anticoagulant in CKRT Using a Porcine Model
Session Information
- Dialysis: Prescription, Physiology, and Treatment Optimization
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 801 Dialysis: Hemodialysis and Frequent Dialysis
Authors
- McMahon, Blaithin A., Medical University of South Carolina, Charleston, South Carolina, United States
- Chawla, Lakhmir S., University of California San Diego, La Jolla, California, United States
- Aslam, MD, Shakil, Georgetown University, Washington, District of Columbia, United States
Background
Nafamostat, a serine protease inhibitor, blocks fibrinogen proteolysis to fibrin. Its half-life of 8 minutes and high dialyzability allows its use as a regional anticoagulant in RRT with minimal impact on the patient's systemic coagulation.. The study was conducted to characterize its pharmacokinetics and its effects on post-filter and systemic activated clotting time (ACT) across different membrane types at clinically relevant prescription parameters in a porcine model of AKI on CKRT.
Methods
Domestic pigs (Yorkshire cross, n = 3) weighing approximately 45 kg were anesthetized and mechanically ventilated with standard settings. Intravenous propofol was administered as required for sedation. Vascular access for RRT was achieved with two 13 Fr double-lumen catheters: one in the right external jugular vein and one in a femoral vein to prevent recirculation. A functional nephrectomy by ligation of all renal arteries to each kidney achieved renal failure. Animals were euthanized at the conclusion of each study.. A point-of-care iSTAT device using a Celite cartridge was used to measure the Activated Clotting Time.
Results
The median (SD) systemic concentrations of nafamostat were 2.8 (2.4) percent of the pre-filter (1.3 to 9.0) concentrations in the polyethersulfone filter, 4.5 (1.9) percent (2.1 to 8.2) in the polyarylethersulfone filter, and 1.8 (1.5) percent (0.5 to 4.3) in the polyacrylonitrile filter at various clinically relevant CKRT prescription parameters (Qb 100-200 ml/min, Qd 35 ml/min). The median (SD) systemic nafamostat concentration was 3.2 (2.2) percent of the pre-filter values across all membranes and prescription parameters. Thus, on average, the CKRT filters removed over 95 percent of the pre-filter nafamostat. The mean (SD) systemic ACT of 145 (13.7) seconds was less than half of the post-filter mean (SD) ACT of 312 (45) seconds. The baseline systemic ACT was 123 seconds. The mean (SD) systemic ACT was 136 (9.2) seconds when the mean (SD) post-filter was under 275 seconds, with the mean (SD) of 257 (7.9) seconds.
Conclusion
When administered pre-filter, over 95 percent of nafamostat was removed by the hemofilter, resulting in systemic exposures less than 5 percent of the circuit exposure. There was a minimal effect on the systemic ACT when the post-filter ACT was less than 275 seconds.Nafamostat may be a suitable candidate for further evaluation as a regional anticoagulant in CKRT.
Funding
- Commercial Support – Talphera Inc