Work described in this thesis was aimed to further understand the role of macrophages in acute cellular rejection of transplanted kidneys, and perform a pre-clinical assessment of the localization... Show moreWork described in this thesis was aimed to further understand the role of macrophages in acute cellular rejection of transplanted kidneys, and perform a pre-clinical assessment of the localization and efficacy of liposomal prednisolone. First, we explored the role of anti-inflammatory macrophages in the onset of acute cellular rejection using human biopsy samples. Here, we discovered that the presence of high levels of CD163+ macrophages was associated with a lower risk of rejection, in a population of patients with a high rate of delayed graft function. Subsequently, we identified the ability of liposomal prednisolone to target macrophages in the kidney using in vitro models of human macrophages, and their ability to accumulate in inflamed kidney tissue in vivo rat models of ischemia reperfusion injury in the kidney. Finally, we evaluated the treatment efficacy of liposomal prednisolone in a mouse model of cellular rejection following kidney transplantation. Here, we were able to show an improved efficacy of liposomal prednisolone in treating rejection, when compared to treatment with free prednisolone. Show less
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
Voorzaat, B.M.; Schaik, J. van; Bogt, K.E.A. van der; Vogt, L.; Huisman, L.; Gabreels, B.A.T.F.; ... ; Rotmans, J.I. 2017
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
