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Updated: Mar 23, 2026
Normothermic Ex Vivo Kidney Perfusion for the Preservation of Kidney Grafts prior to Transplantation
Published on: July 15, 2015
Attenuating Ischemia-Reperfusion Injury in Kidney Transplantation by Perfusing Donor Organs With siRNA Cocktail
Xiufen Zheng1, GuoYao Zang, Jifu Jiang
11 Departments of Pathology, Surgery, Oncology and Biostatistics, University of Western Ontario, Ontario, Canada. 2 Lawson Health Research Institute, London, Ontario, Canada. 3 London Health Sciences Centre; London, Ontario, Canada. 4 Zhejiang University, Sir Run Run Shaw Hospital, Hangzhou, China.
Background:
Ischemia-reperfusion (I/R) injury is the major cause of delayed renal graft function in kidney transplantation. To date, there are no effective therapeutic approaches for preventing I/R injury. We previously reported that treatment of animals with small interference RNA (siRNA) would prevent warm I/R injury in nontransplant models and cold I/R injury in heart transplantation. In the present study, we further explore the feasibility of protecting grafts from extended cold I/R injury as applied to kidney transplantation by downregulating I/R-associated genes using siRNA.
Methods:
Donor kidneys were intra-arterially perfused with siRNA containing solution during donor excision and preserved in siRNA containing solution. The siRNA-treated donor organs were then implanted into syngeneic recipient mice, and the 2 original kidneys were removed from the recipient. The effect of siRNA solution on extended cold I/R injury was determined by assessing renal function, histopathological change, cell apoptosis, and inflammation.
Results:
The perfused siRNA solution knocked down the expression of complement 3, RelB, and Fas in the kidney at the mRNA and protein levels. Administration of siRNA solution reduced the levels of blood urea nitrogen and serum creatinine as compared with control groups. The siRNA cocktail decreased cell apoptosis and histopathological changes in the kidney and prolonged graft survival. The siRNA cocktail also reduced the expression of proinflammatory cytokines, IL-6, and TNFα.
Conclusions:
In conclusion, this is the first demonstration that perfusing donor organs with an siRNA cocktail solution can induce gene silencing in the kidney and prevent kidneys from extended cold I/R injury in kidney transplantation, highlighting the promise of the clinical application of siRNA-based therapies in the preservation of donor organs.
Insights
Small interference RNA (siRNA) prevents kidney transplant injury by downregulating specific genes. This novel approach protects donor organs from cold ischemia-reperfusion injury, offering promise for clinical application.
Area of Science:
- Nephrology
- Transplantation Immunology
- Molecular Biology
Background:
- Ischemia-reperfusion (I/R) injury is a primary cause of delayed graft function in kidney transplantation.
- Current therapeutic options for preventing I/R injury remain limited.
- Previous studies demonstrated siRNA efficacy in preventing I/R injury in non-transplant and cardiac models.
Purpose of the Study:
- To investigate the potential of small interference RNA (siRNA) in preventing extended cold I/R injury in kidney transplantation.
- To assess the feasibility of downregulating I/R-associated genes using siRNA for graft protection.
Main Methods:
- Donor kidneys were perfused and preserved with an siRNA-containing solution.
- siRNA-treated kidneys were transplanted into recipient mice, with native kidneys removed.
- Renal function, histopathology, apoptosis, and inflammation were evaluated to determine siRNA efficacy.
Main Results:
- siRNA perfusion effectively reduced mRNA and protein levels of complement 3, RelB, and Fas.
- siRNA treatment significantly lowered blood urea nitrogen and serum creatinine levels.
- The siRNA cocktail decreased apoptosis, improved kidney histology, reduced inflammatory cytokines (IL-6, TNFα), and prolonged graft survival.
Conclusions:
- This study demonstrates that perfusing donor kidneys with an siRNA cocktail can achieve gene silencing and prevent extended cold I/R injury.
- This represents the first evidence of siRNA-based therapy for donor organ preservation in kidney transplantation.
- The findings highlight the significant potential of siRNA therapies for clinical application in safeguarding transplanted organs.
Related Concept Videos
01:28Kidney Transplant I: Introduction
01:26Kidney Transplant II: Surgical Procedure