The vascular access is the Achilles' heel of hemodialysis. This thesis focuses on the maturation and long-term outcomes of arteriovenous fistulas and compares them to arteriovenous grafts. Also the... Show moreThe vascular access is the Achilles' heel of hemodialysis. This thesis focuses on the maturation and long-term outcomes of arteriovenous fistulas and compares them to arteriovenous grafts. Also the results from the LIPMAT-study are presented, a randomized controlled trial in which improvement of arteriovenous fistula maturation using liposomal prednisolone was evaluated. Finally, cardiac effects of arteriovenous fistulas are explored. Show less
Dysfunction of vascular access remains a major clinical problem responsible for high morbidity and substantial health care costs in patients required chronic hemodialysis treatment. Despite the... Show moreDysfunction of vascular access remains a major clinical problem responsible for high morbidity and substantial health care costs in patients required chronic hemodialysis treatment. Despite the magnitude of this clinical problem, there have been no major novel therapeutic interventions in the field of hemodialysis access for the past few decades. The work described in this thesis aimed to further understand the pathobiology of vascular access dysfunction and identify new therapeutic candidates to improve the current status of hemodialysis vascular access.We first explored the role of inflammation in vascular remodeling upon arteriovenous fistula (AVF) surgery. Based on the evolving concept of the importance of the outward remodeling (OR) in AVF maturation next, we evaluated the role of relaxin pathway as potential contributor to OR in AVF maturation. In parallel with testing new therapeutics to improve maturation and patency of native AVFs, our group is working on developing tissue engineered blood vessels (TEBVs) which could offer a suitable alternative for arteriovenous conduits. In collaboration with University of California, Los Angeles, we performed a lineage tracing to study the contribution of bone marrow derived cells to TEBV formation and the impact of chronic kidney disease onto the process of TEBV formation. Show less
Hemodialysis is the most widely used option in chronic dialysis treatment and requires a suitable vascular access. Unfortunately, this vascular access suffers from a high number of failures... Show moreHemodialysis is the most widely used option in chronic dialysis treatment and requires a suitable vascular access. Unfortunately, this vascular access suffers from a high number of failures responsible for a high morbidity and health care costs. However, the exact pathophysiology remains unclear. In order to unravel the mechanisms of arteriovenous fistula failure we developed a novel murine model of arteriovenous fistula failure. Using this model, we studied the effects of vascular remodeling in mice that were haplodeficient for the eln gene. The role of inflammation in arteriovenous remodeling was also investigated by administrating liposomal prednisolone and by incorporating RP105 knockout mice. Show less
