NIV Congres

Kidneys derived from deceased brain dead (DBD) donors have inferior outcomes after transplantation compared to kidneys from living donors. Also, DBD donors suffer from bacterial translocation and endotoxemia. A link between Angiopoietin 1 (Ang1), Angiopoietin 2 (Ang2) and endotoxemia has been established. Ang1 and Ang2 are antagonictic ligands that bind to the Tie2 receptor. We aimed to modify the Ang1 levels in our brain death rat model to clarify whether exogenous administration of Ang1 has a protective role and may be of therapeutical value to improve outcome after DBD transplantation.

We administrated 0,1µg/kg Ang1 or  0,9% saline 30 min before brain death (BD) induction. BD was induced by inflating a subdurally placed balloon catheter in rats. Two groups of sham operated animals were injected with either Ang1 or 0,9% saline (n = 7 for all groups). The animals were monitored for 4 hrs. Just before sacrificing the animals blood was collected and kidneys were harvested for histology and PCR.

Plasma levels of ALT, AST, creatinine, LDH and urea increased in the BD groups compared to sham operated groups (p<0.05). The 2fold induction of E-selectin, P-selectin, VCAM-1, ICAM-1, IL-6, KIM-1 and HO-1 in the kidney is elevated in the BD groups compared to the sham operated groups (p<0.05). The renal TNF-α fold induction of the BD+Ang1 group is increased compared to both sham groups (p<0.05). Tie2 fold induction in the kidney is not influenced by Ang1 administration and decreased significantly in the BD groups (mean fold induction 0.45 BD+saline and 0.38 BD+Ang1) compared to the sham groups (mean fold induction 2.5 sham+saline and 2.6 sham+Ang1).

Functional and inflammatory markers were increased in the BD groups and not affected by this dosage of Ang1. These results show a remarkable effect of brain death on Tie2 fold induction. This reduction suggests a functional role for Tie2 in BD which could not be compensated by administrating Ang1.