Towards optimal conditions for endothelial integrity during ex vivo kidney machine perfusion

This thesis describes the effect of ex vivo machine perfusion of donor kidneys on the integrity of the endothelium. The endothelium is crucial for renal function and plays a significant role in acute and chronic kidney damage. The endothelium consists of a single layer of endothelial cells (ECs) located at the luminal site of blood vessels, covered with the endothelial glycocalyx (eGC). The eGC plays a crucial role in various processes and is composed of a dynamic network of proteins and carbohydrates. The eGC is essential for proper endothelial function. Therefore, the loss of ECs and the glycocalyx is detrimental to the physiological properties of the kidney. In transplantation, machine perfusion is a method to preserve donor kidneys, assess their quality, and potentially improve them if they do not meet standard quality requirements. This thesis demonstrates that both hypothermic and normothermic machine perfusion are associated with eGC loss. Although machine perfusion is a valuable and promising technique with desirable properties for the preservation, the observed eGC loss deserves further investigation to better understand the consequences and extent of this endothelial damage in the clinical setting. The knowledge obtained in this thesis, along with future research, can contribute to optimizing the integrity of the endothelium during ex vivo machine perfusion of kidneys and improving transplant outcomes.