Exendin-4 for Donor Treatment in a Brain-Death Model of Kidney Transplantation

H. Yang¹, L. Luo¹, X. Li¹, C. Long¹, Y. Shi², Y. Xiong³, M. Chen⁴, J. Gao⁵, H. Li⁶, Z. Wang⁶

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 Vascular Surgery, People's hospital of Jiangxi Province, Nanchang, China, ⁶Department of Urologic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Meeting: 2019 American Transplant Congress

Abstract number: C10

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

Session Information

Session Name: Poster Session C: Immunosuppression Preclinical Studies

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: Renal grafts from brain death donors associated with poorer graft outcomes after kidney transplantation, hemodynamic and inflammatory mechanisms can account for brain death induce kidney injury. Glucagon-like peptide-1 receptor (GLP-1R) agonist is known as Exendin-4 exerts protective effects against ischemia and inflammatory. This study investigated the potential use of Exendin-4 in donor management to ameliorate the damage caused by brain death and ischemia-reperfusion injury in a rat model of kidney transplantation.

*Methods: Brain-dead Fisher rats were treated immediately after induction of brain death with Exendin-4 or vehicle for 6 hours. Orthotopic kidney transplantation were performed in Lewis recipient rats. The right donor kidneys were stored for morphology and reverse transcriptase-polymerase chain reaction. Blood samples were taken and on several days after transplantation from the recipient. All kidney grafts were harvested for morphology and immmunohistology analysis after 7 days.

*Results: There was no effect on donor heart rate and blood pressure under Exendin-4 treatment. The right kidneys from Exendin-4 pretreatment animals revealed diminished mRNA expression of the proinflammatory cell adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and Caspase-3. Furthermore, Exendin-4 had significantly reduced TUNEL+ cells in donor kidneys. Recipients receiving a renal allograft from Exendin-4 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, moreover, Exendin-4 treatment significant decreased CD4, CD8, MHCII and ED1 cell infiltration.

*Conclusions: Donor treated with Exendin-4 immediately after brain death leads to better graft function and reduced acute rejection compare to untreated renal allograft recipients.

To cite this abstract in AMA style:

Yang H, Luo L, Li X, Long C, Shi Y, Xiong Y, Chen M, Gao J, Li H, Wang Z. Exendin-4 for Donor Treatment in a Brain-Death Model of Kidney Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/exendin-4-for-donor-treatment-in-a-brain-death-model-of-kidney-transplantation/. Accessed November 21, 2024.

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