Leiden University Scholarly Publications

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Alem, C.M.A. van (2023)

Targeting macrophages in renal transplantation

Doctoral Thesis
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 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...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.
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Kidney transplantation
Macrophages
Liposomal prednisolone
Treatment effect
Animal model
All authors
Alem, C.M.A. van
Supervisor
Rotmans, J.J.; Kooten, C. van
Committee
Meijer, O.C.; Eikmans, M.; Reinders, M.E.J.; Florquin, S.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2023-04-13
ISBN (print)
9789493278387

Funding

Sponsorship
The research described in this thesis was performed at the Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands, with financial support from an unrestricted grant from Enceladus Pharmaceuticals, a VIDI grant (016.156.328) awarded to J.I. Rotmans, and a research fellowship from the ERA-EDTA Young Fellowship program (RSTF 1223/2017) awarded to C.M.A. van Alem