Abstract: TH-PO1002
Preserving Kidney Graft Function in a Mouse Model of Donation After Circulatory Death with Necrostatin-1 by Reducing RIPK1-Mediated Cell Death
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
- Tran, Minh Hoang, University of South Florida, Tampa, Florida, United States
- Rani, Alka, University of South Florida, Tampa, Florida, United States
- Wang, Lei, University of South Florida, Tampa, Florida, United States
Background
The shortage of donor organs has led to utilization of donors after circulatory death (DCD). However, DCD kidneys are often associated with impaired graft quality and increased risk of graft dysfunction after transplantation. Receptor-interacting protein kinase 1 (RIPK1)-mediated cell death is a key contributor to ischemia-reperfusion injury and kidney graft dysfunction. We investigated whether Necrostatin-1-mediated RIPK1 inhibition preserves graft function and mitigates both short- and long-term graft injury in a mouse model of DCD kidney transplantation.
Methods
Male C57BL/6J mice, aged 10-12 weeks (25-35g), were induced cardiac arrest of 7 minutes (intravenous KCl, 200 mg/kg, 1 mM). Same-sex and same-age recipient mice were given Nec-1 (treatment) or vehicle (control) prior to transplantation. Plasma and urine samples were collected at 1, 3, and 7 days for short -term and 30 days for long-term graft injury and function analysis. Kidney graft tissue was collected at the end of experiment for histology, protein assay analyses, and real-time PCR.
Results
Nec-1 treatment preserved donor organ quality and improved kidney graft function, demonstrated by 38%–42% reductions in plasma creatinine and KIM-1 levels compared with vehicle-treated controls. PAS and TUNEL stains of kidney graft sections revealed preserved graft architecture, reduced tubular injury, and decreased cell death in the Nec-1-treated group. Pico-Sirius Red stains showed reduced collagen deposition associated with tubular injury in treated grafts. Western blotting showed reduced expression of phosphorylated MLKL (p-MLKL) and phosphorylated RIPK1 (p-RIPK1) in the Nec-1-treated group, indicating suppression of RIPK1-mediated necroptotic cell death pathways. Long-term follow-up demonstrated improved BUN and proteinuria levels, as well as reduced interstitial fibrosis on histological assessment.
Conclusion
In summary, Nec-1 treatment reduced RIPK1-mediated cell death, attenuated tubular injury and fibrosis, and preserved renal function following DCD kidney transplantation. Administration of Nec-1 to both donors and recipients conferred additional protection and further improved graft outcomes. These findings suggest dual targeting of RIPK1-mediated cell death in both donors and recipients represents a promising therapeutic strategy to enhance transplant outcomes of DCD kidney grafts.