Microvascular alterations in transplantation

Abstract

Endothelial injury and repair are most important concepts for our understanding of renal disease and allograft injury. The concept that injury to the endothelium may precede renal fibrosis strongly suggests that interventions to maintain vascular integrity are of major importance for renal function. This thesis focuses on the mechanisms involved in the process of endothelial damage and repair in renal disease, (early) diabetes mellitus (DM) and renal ischemia-reperfusion (I/R) injury. Furthermore, microvascular alterations were assessed, using sidestream darkfield (SDF) imaging and measurement of endothelial dysfunction markers (including angiopoietins), in chronic kidney disease (CKD) and DM patients before and after (pancreas) kidney transplantation. The results of this thesis demonstrate an important role for endothelial damage and repair in renal disease and after transplantation. Both renal I/R and DM induced systemic capillary damage reflected by increased capillary tortuosity by SDF imaging and a dysbalance in angiopoietins. In addition, patients with CKD and allograft rejection after renal transplantation also had systemic microvascular derangements. Transplantation was effective in reversing the systemic microvascular alterations. Complementary use of SDF imaging to measure microvascular tortuosity and the assessment of endothelial dysfunction markers may be useful diagnostic tool for monitoring the microvasculature before and after transplantation.