Date: Monday, June 3, 2019
Session Name: Poster Session C: Immunosuppression Preclinical Studies
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 February 24, 2020.
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