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Master Thesis

Syndrome de Gordon-like induit par les anticalcineurines : une approche clinique et biochimique

Abstract : Calcineurin inhibitors (CNI) are immunosuppressive treatments widely used in transplantation. In mice, CNI activate the renal NaCl cotransporter (NCC), and thereby they cause high blood pressure, metabolic acidosis and hyperkalemia. This association of symptoms is also observed in patients suffering Gordon syndrome, a genetic disease also caused by inappropriate stimulation of NCC. Recently, it has been reported that acidosis of Gordon syndrome also involves stimulation of the Cl-/HCO3- exchanger pendrin. In humans, little is known about the prevalence of Gordon-like syndrome phenotype in patients treated with CNI. Interestingly, NCC and pendrin expression can be assessed by immunoblots using urinary exosomes, small extracellular vesicles that reflect the composition of the plasma membrane of their parental cells. We designed two studies including incident CNI-treated kidney transplants 3 months after transplantation: a retrospective study was designed to determine the prevalence of Gordon-like phenotype, then a prospective one to evaluate NCC and pendrin expression in urinary exosomes. 172 patients were included in the retrospective study: 26% exhibited Gordon-like syndrome phenotype. Then, 58 patients were prospectively included and compared to 58 healthy volunteers. Again ~ 24% of kidney transplant recipients exhibited the Gordon-like phenotype. We show, however, that KT with Gordon-like phenotype do not exhibit a significant increase in NCC, pNCC or pendrin abundance. Furthermore, we show that CNI-treated KT have a marked down regulation of NCC, pNCC protein abundance in urinary exosomes compared to healthy volunteers.
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https://dumas.ccsd.cnrs.fr/dumas-02418474
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Submitted on : Wednesday, December 18, 2019 - 6:52:14 PM
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Ludovic Di Ascia. Syndrome de Gordon-like induit par les anticalcineurines : une approche clinique et biochimique. Sciences du Vivant [q-bio]. 2019. ⟨dumas-02418474⟩

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