Abstract: FR-PO855
Effect of Deceased Donor Inflammatory Pathways on Chronic Renal Graft Dysfunction
Session Information
- Transplantation: Basic
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1801 Transplantation: Basic
Authors
- Diaz Encarnacion, Montserrat M., Fundación Pugvert, Barcelona, Spain
- Guillen-gomez, Elena, Fundación Puigvert, Barcelona, Spain
- Dasilva Santos, Iara, Fundacio Puigvert, BARCELONA, Spain
- Silva, Irene, FUNDACION PUIGVERT, BARCELONA, Spain
- Guirado, Lluis, Fundació Puigvert, Barcelona, Spain
- Serra, Nuria, Fundació puigvert, Barcelona, Spain
Background
In deceased donor (DD) renal transplantation an inflammatory activity is established prior to nephrectomy. It produces macrophage infiltration and has been associated with the onset of fibrosis. Adenosine exerts its anti-inflammatory activity mainly through the A2A receptor. Monocytes and macrophages release TNF-α which induces A2A activity and mediates renal interstitial fibrosis through an increase in TGF-β1 and macrophage M2 switching. The aim of this study is to determine the effect of DD inflammation on chronic renal graft dysfunction.
Methods
Samples of pre-implantation renal tissue, 17 from living donor (LD) and 40 from DD were analyzed by Real-time PCR with the TaqMan® OpenArray® and western-blot.
Results
Infiltration of macrophages in DD kidneys was significantly greater than in LD. The expression of TNF-α, TGF-β1 and A2A was also higher than in LD and correlated positively with each other. A2A receptor also correlated with: pro-fibrotic markers such as α-SMA, fibronectin, vimentin, and collagen; the enzyme adenylate cyclase and the M2 macrophage marker CD163, C/EBPβ and IL-10, which are most expressed in DD kidneys. Western-blot results show PKA and CREB activation and increased CD163 and A2A protein translation.
Conclusion
TNF-α-mediated inflammation in DD kidneys is associated with the increase/activation of anti-inflammatory factors such as TGF-β1 and adenosine receptor A2A. Our results indicate that the activation of this pathway induces PKA-mediated CREB phosphorylation, which in turn stimulates transcription of C/EBPβ and promotes the induction of factors that could lead to fibrosis in the renal graft via M2 macrophages.
Funding
- Government Support - Non-U.S.