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mTORC Pathway Activation and Effect of Sirolimus on Native Kidney Antiphospholipid Syndrome Nephropathy: A Case Report.
Dufour, Inès; Venot, Quitterie; Aydin, Selda; Demoulin, Nathalie; Canaud, Guillaume; Morelle, Johann.
Afiliación
  • Dufour I; Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium.
  • Venot Q; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM U1151, Institut Necker Enfants Malades, Paris, France.
  • Aydin S; Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium; Department of Histology, Cliniques universitaires Saint-Luc, Brussels, Belgium.
  • Demoulin N; Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium.
  • Canaud G; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM U1151, Institut Necker Enfants Malades, Paris, France; Service de Néphrologie Transplantation Adultes, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
  • Morelle J; Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium. Electronic address: johann.morelle@uclouvain.be.
Am J Kidney Dis ; 76(2): 288-291, 2020 08.
Article en En | MEDLINE | ID: mdl-31810732
Despite optimal anticoagulation and blood pressure control, patients with antiphospholipid syndrome (APS) nephropathy frequently progress to kidney failure, and recurrence after transplantation is common. The mTORC (mechanistic target of rapamycin complex) pathway was recently identified as a potential intermediate and a therapeutic target in vascular lesions associated with APS nephropathy. However, these results were derived from the retrospective analysis of a small cohort of patients receiving sirolimus after kidney transplantation. Therefore, they warranted external validation and the demonstration of the potential benefit of sirolimus in native kidney APS nephropathy. We report a patient with active APS nephropathy lesions occurring on native kidneys, in which endothelial mTORC activation was substantiated at the molecular level. Treatment with sirolimus was shown on a repeat kidney biopsy to successfully inhibit the AKT/mTORC pathway and was associated with significant improvement in kidney function and lesions of vasculopathy. Drug tolerance was excellent during the entire follow-up. This case validates and extends previous observations in kidney transplant recipients and demonstrates that endothelial activation of the AKT/mTORC pathway occurs in the damaged renal vasculature of native kidneys in APS nephropathy. These findings further support the potential of precision medicine and the use of mTORC activation as a biomarker of disease activity and as therapeutic target in patients with APS nephropathy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome Antifosfolípido / Sirolimus / Insuficiencia Renal Crónica / Serina-Treonina Quinasas TOR / Diana Mecanicista del Complejo 1 de la Rapamicina / Diana Mecanicista del Complejo 2 de la Rapamicina / Inmunosupresores Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Adult / Female / Humans Idioma: En Revista: Am J Kidney Dis Año: 2020 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome Antifosfolípido / Sirolimus / Insuficiencia Renal Crónica / Serina-Treonina Quinasas TOR / Diana Mecanicista del Complejo 1 de la Rapamicina / Diana Mecanicista del Complejo 2 de la Rapamicina / Inmunosupresores Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Adult / Female / Humans Idioma: En Revista: Am J Kidney Dis Año: 2020 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos