Abstract: TH-PO0990
Anti-C5 Therapy Improves Kidney Outcomes After Donation After Circulatory Death Kidney Transplantation with Static Cold Storage and Provides Additional Benefit to Ex Vivo Machine Perfusion in a Rat Model
Session Information
- Transplantation: Basic - Immune Biology, Tissue Injury, and Emerging Technologies
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2001 Transplantation: Basic
Authors
- Mital, Jeff, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Hughes, Benjamin, Duke University Medical Center, Durham, North Carolina, United States
- Zhang, Min, Duke University Medical Center, Durham, North Carolina, United States
- Bohrer, Conor A., Duke University Medical Center, Durham, North Carolina, United States
- Arnold, Charles J., Duke University Medical Center, Durham, North Carolina, United States
- Wang, Bangchen, Duke University Medical Center, Durham, North Carolina, United States
- Zhang, Yuchun, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Bouchard, Keith, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Kim, Sung-Kwon, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Thakar, Ketan, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Belcourt, Michael, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Esteghamat, Sahar, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Tarabar, Sanela G., Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Singh, Ajay K., Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Ramanujam, Meera, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Barbas, Andrew S., Duke University Medical Center, Durham, North Carolina, United States
Background
Delayed graft function (DGF) is a major complication of donation after circulatory death (DCD) kidney transplantation. Complement activation is a major driver of ischemia-reperfusion injury and the development of DGF, but the benefit of terminal complement inhibition in clinically relevant DCD settings is uncertain. We evaluated whether recipient anti-C5 treatment improves DCD kidney transplantation outcomes following static cold storage (SCS) or ex vivo machine perfusion (EVMP) of the kidney in a rat model.
Methods
A rat DCD kidney transplant model was established using 15 minutes of warm ischemia followed by 18 hours of cold ischemia prior to syngeneic kidney transplant. Cold ischemia was maintained under either static or hypothermic EVMP conditions. Recipient rats were treated with anti-C5 (20 or 40 mg/kg) or vehicle 2 hours prior to transplantation and on PODs 4, 7, and 11. Outcomes were compared across SCS alone, SCS + anti-C5, EVMP alone, and EVMP + anti-C5 groups. Survival and renal injury were assessed using serum creatinine (sCr) and blood urea nitrogen (BUN) throughout the 14-day follow-up.
Results
In the SCS model, anti-C5 improved survival by 45% at 20 mg/kg (n=4) and 29% at 40 mg/kg (n=6) vs. vehicle (n=9). However, only the 40 mg/kg dose of anti-C5 improved kidney function, reducing postoperative day 1 (POD1) sCr and BUN by approximately 25% vs. vehicle. The 20 mg/kg dose improved survival without improvement in renal function biomarkers. EVMP alone (n=6) improved survival to 100% and reduced POD1 renal injury biomarkers (sCr by 47%; BUN by 37%). Adding recipient 40 mg/kg anti-C5 treatment to EVMP (n=4) further improved renal function with 32% lower sCr and BUN at POD1, compared with EVMP alone. The reduction in POD1 sCr for EVMP + 40 mg/kg anti-C5 compared with SCS alone reached statistical significance.
Conclusion
In this rat DCD kidney transplant model, recipient anti-C5 therapy improved outcomes after SCS in a dose-dependent manner, with the higher dose improving survival and kidney function. EVMP improved survival and renal injury compared with SCS. Anti-C5 provided additional renal benefit when combined with EVMP. These findings support terminal complement inhibition as a strategy to reduce DGF in DCD kidney transplantation, both with SCS and as an addition to machine perfusion.
Funding
- Commercial Support – Alexion, AstraZeneca Rare Disease