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16:00 - 17:45

Angiopoietin2: a prognostic marker in kidney transplantation

Westendorp, W.H., Koudstaal, L.G., Damman, J., Burgerhof, J.G., Seelen, M.A., Goor, H. van, Ploeg, R.J., Leuvenink, H.G. D.

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Organs derived from deceased brain dead (DBD) donors show worse organ function and more acute rejection episodes than organs derived from living donors. Human studies have provided evidence that DBD donors suffer from bacterial translocation and higher endotoxin load. A link between endotoxemia and Angiopoietin 2 (Ang2) is established. In humans, LPS triggers Ang2 release, which binds to the Tie2 receptor. Use of Ang2 as biomarker of endothelial integrity has gained much attention since Ang2 reflects the immunogenic state of an organ and could therefore be used as a predictor of organ quality and survival.

 

We measured serum Ang2 by ELISA in 100 DBD and 220 living donors (LD). Serum was obtained immediately after the declaration of brain death (T0) and just before organ retrieval (T1). Serum from living kidney donors retrieved after start of the operation (T0) and just prior to organ retrieval (T1) was used as control.

 

Serum Ang2 levels in DBD donors are higher at T0 and T1 (T0: 1925 ± 198.9 pg/ml and T1: 2418 ± 305.2 pg/ml) compared to living donors (T0: 690.7 ±  47.60 pg/ml and T1: 1384 ± 102.9 pg/ml). In LD, Ang2 levels increased at T1 compared to T0 (p<0.05). In LD, T1 Ang2 levels are associated with glomerular filtration rate (GFR) at 12 months after transplantation (Spearman’s ρ -0.193 p=0.019). In DBD donors, T0 Ang2 levels are associated with serum creatinin 14 days after transplantation (Spearman’s ρ -0.333 p=0.017).

 

These results show elevated Ang2 levels in DBD compared to LD, which is illustrative of an inflammatory response. A clinical validated Ang2 test and therapeutic interventions that modulate the Ang2 response in the DBD donor might be novel tools to improve organ quality.