Abstract: SA-PO0264
FXIa Inhibition Protects Against Cholesterol Crystal Embolism-Induced AKI Without Increasing Bleeding
Session Information
- AKI: Mechanisms - Cell Signaling
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Fei, Ye, LMU Klinikum Medizinische Klinik und Poliklinik IV, Munich, BY, Germany
- Ku, John, LMU Klinikum Medizinische Klinik und Poliklinik IV, Munich, BY, Germany
- Yildirim, Mome, LMU Klinikum Medizinische Klinik und Poliklinik IV, Munich, BY, Germany
- Anders, Hans J., LMU Klinikum Medizinische Klinik und Poliklinik IV, Munich, BY, Germany
Background
Cholesterol crystal embolism (CCE) causes AKI through microvascular occlusion and neutrophil-driven immunothrombosis. Whether FXIa inhibition protects without bleeding is unknown.
Methods
C57BL/6J mice underwent CCE-AKI induced by cholesterol crystals (10 mg/kg). Asundexian, rivaroxaban, or argatroban was tested across -0.5 to 9 h windows. Outcomes included GFR, TTC infarct size, bleeding, urinary RBCs, immunofluorescence, flow-chamber assays, scRNA-seq and bulk RNA-seq.
Results
CCE reduced GFR from 293.9+/-7.9 to 117.7+/-11.2 uL/min. Asundexian preserved GFR through 9 h (161.6+/-10.0 uL/min; p<0.01), while comparators were less durable. It reduced TTC infarct size at 9 h (60.6+/-3.1% vs 34.5+/-3.4%; p<0.001), did not prolong bleeding, and did not increase urinary RBCs versus saline (11.6+/-1.2 vs 10.7+/-1.4 RBC/HPF, NS). Asundexian reduced kidney-vessel NETs, neutrophils, platelets and neutrophil-platelet co-localization, and suppressed platelet activation/NET formation.
Conclusion
Asundexian protects against CCE-AKI without increasing bleeding, supporting FXIa-driven immunothrombosis as a targetable injury pathway.
Figure 1
Asundexian preserves GFR, reduces infarct size, and avoids bleeding in CCE-AKI.
Figure 2
Asundexian suppresses neutrophil-platelet immunothrombosis in CCE-AKI.
Funding
- Government Support – Non-U.S.