Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) are involved in stabilizing the vascular endothelium and may play a role in premature mortality and graft failure in renal transplant recipients (RTR). Early identification of RTR at risk could allow for management, possibly via anti-Ang2 therapy. We aimed to investigate the association of Ang1 and Ang2 with graft failure and mortality in a prospective cohort of stable, outpatient RTR.

Since elevated Ang2 levels have been demonstrated in sepsis, which has pathophysiological similarities to the deceased brain dead donor we also separately studied Ang2 associations in RTR transplanted with deceased donor kidneys.

Plasma Ang1 and Ang2 next to clinical parameters were measured in 552 RTR and in 86 living kidney donors (LKD).

Ang1 was higher in RTR than in LKD (p=0.002), while Ang2 was similar. Surprisingly, in a multivariate analysis, significant associations between Ang2 and heart rate, Nt-pro-BNP or hsCRP were found (all p<0.001) while for Ang1, no associations were found. In deceased donor-RTR, Ang2 levels were higher compared to living donor-RTR. After adjustment for potential confounders, Ang2 levels were both associated with graft failure (HR 2.41, 95%CI 1.24-4.71, p=0.01) and mortality (HR 1.53, 95%CI 1.03-2.27, p=0.04) after deceased donation.

Intervention studies targeting Ang2 to attenuate inflammation are required to provide insight in the mechanism of the Ang/Tie2-system in renal transplantation, especially after deceased donation.

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