Renal ischemia-reperfusion induces release of angiopoietin-2 from human grafts of living and deceased donors

BACKGROUND: Recent insights suggest that endothelial cell (EC) activation plays a major role in renal ischemia-reperfusion (I/R) injury. Interactions between ECs and pericytes via signaling molecules, including angiopoietins, are involved in maintenance of the vascular integrity. Experimental data have shown that enhancement of Angiopoietin (Ang)-1 signaling might be beneficial in renal I/R injury. However, little is known about the role of angiopoietins in human renal I/R injury.

METHODS: In this study, EC activation and changes in angiopoeitins are assessed in human living-donor (LD) and deceased-donor (DD) kidney transplantation. Local release of angiopoietins was measured by unique, dynamic arteriovenous measurements over the reperfused kidney.

RESULTS: Renal I/R is associated with acute EC activation shown by a vast Ang-2 release from both LD and DD shortly after reperfusion. Its counterpart Ang-1 was not released. Histologic analysis of kidney biopsies showed EC loss after reperfusion. Baseline protein and mRNA Ang-1 expression was significantly reduced in DD compared with LD and declined further after reperfusion.

CONCLUSIONS: Human renal I/R injury induces EC activation after reperfusion reflected by Ang-2 release from the kidney. Interventions aimed at maintenance of vascular integrity by modulating angiopoietin signaling may be promising in human clinical kidney transplantation.