Targeting Pyroptosis in Brain-Dead Donors Improves Renal Function after Transplantation in Rat

H. Yang¹, Y. Shi², X. Li¹, L. Luo¹, C. Long¹, Y. Xiong³, M. Chen⁴, J. Gao⁴, H. Li⁵, Z. Wang⁵

¹Department of Organ Transplantation, People's Hospital of Jiangxi Province, Nanchang, China, ²Department of Pathology, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ³Department of Neurology, People's Hospital of Jiangxi Province, Nanchang, China, ⁴Department of Vascular Surgery, People's Hospital of Jiangxi Province, Nanchang, China, ⁵Department of Urologic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Meeting: 2019 American Transplant Congress

Abstract number: C20

Keywords: Brain death, Inflammation, Kidney transplantation, Renal injury

Session Information

Session Name: Poster Session C: Innate Immunity; Chemokines, Cytokines, Complement

Session Type: Poster Session

Date: Monday, June 3, 2019

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

*Purpose: Pyroptosis is a form of programmed cell death include necrosis, nuclear condensation, and release of proinflammatory after caspase-1 activation. It is unknown whether pyroptosis mechanism is involved in brain death induce inflammatory response. This study investigated the effects of a caspase-1 inhibitor, Ac-YVAD-CMK on brain death induce kidney injury and ischemia-reperfusion injury in a rat model of kidney transplantation.

*Methods: Brain-dead Fisher rats were treated immediately after induction of brain death for 6 hours with Ac-YVAD-CMK or vehicle. Orthotopic kidney transplantation were performed in Lewis recipient rats. The right donor kidneys were stored for morphometric and molecular biological analysis. Blood samples were taken from the donor and on 1, 3, 5, 7 day after transplantation from the recipient. All kidney grafts were harvested for morphology analysis after 7 days.

*Results: There was no effect on donor heart rate and blood pressure under Ac-YVAD-CMK treatment. Caspase-1, ASC, NLRP3, and AIM2 expressions in the right kidneys with immunohistochemistry and western blot analysis, serum interleukin-1β and -18 were greatly elevated, indicating that pyroptosis occurred in the kidney injury. Ac-YVAD-CMK treatment significantly protected against pyroptosis, reduced TUNEL+ cells, diminished mRNA expression of the proinflammatory interleukin-1β and -18. Furthermore, recipients receiving a renal allograft from Ac-YVAD-CMK treatment donors had a significantly better renal function at day 1 after transplantation. Banff-grading after 7 days showed significantly reduced scores for tubulitis and vasculitis in the grafts of these recipients.

*Conclusions: Pyroptosis is involved in brain death induce kidney injury. Donor treated with caspase-1 inhibitor immediately after brain death leads to better graft function and reduced acute rejection compare to untreated renal allograft recipients after kidney transplantation.

To cite this abstract in AMA style:

Yang H, Shi Y, Li X, Luo L, Long C, Xiong Y, Chen M, Gao J, Li H, Wang Z. Targeting Pyroptosis in Brain-Dead Donors Improves Renal Function after Transplantation in Rat [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/targeting-pyroptosis-in-brain-dead-donors-improves-renal-function-after-transplantation-in-rat/. Accessed November 21, 2024.

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