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Unravelling the mechanisms of kidney fibrosis induced by calcineurin inhibitors.

Boek - Dissertatie

Renal transplantation is the preferred treatment for end-stage renal disease, because of superior outcome and lower costs than dialysis care. The introduction of calcineurin inhibitors (CNI) to suppress rejection episodes in the transplantation of kidneys and other organs resulted in a major improvement of graft survival. However, the long-term use of CNIs is associated with the appearance of renal fibrosis, a declining renal function, and an accelerated return to dialysis. This CNI-associated nephrotoxicity is also encountered in other diseases characterized by the long-term treatment with CNIs. Until now, several cellular mechanisms have been identified in the pathogenesis of kidney fibrosis, but the exact mechanisms for CNI-associated nephrotoxicity are not known. CNIs are metabolized in the proximal tubule cells (PTC) of the kidney. Previously, we demonstrated an increased production of hypoxia-related together with pro-fibrotic factors in response to CNI exposure in our patient-derived model of PTCs. In the current project, we will use this important clue to further elucidate the underlying mechanisms of kidney fibrosis induced by CNIs. We will analyze the potential mechanisms that could be responsible for this phenomenon from different angles. Our findings will be validated by using a large biobank derived from our renal transplant cohort. The findings from this study can offer novel tools for diagnostic and therapeutic interventions.
Jaar van publicatie:2021
Toegankelijkheid:Embargoed