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mTORC Pathway Activation and Effect of Sirolimus on Native Kidney Antiphospholipid Syndrome Nephropathy: A Case Report.

Authors
  • Dufour, Inès1
  • Venot, Quitterie2
  • Aydin, Selda3
  • Demoulin, Nathalie1
  • Canaud, Guillaume4
  • Morelle, Johann5
  • 1 Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium. , (Belgium)
  • 2 Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM U1151, Institut Necker Enfants Malades, Paris, France. , (France)
  • 3 Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium; Department of Histology, Cliniques universitaires Saint-Luc, Brussels, Belgium. , (Belgium)
  • 4 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. , (France)
  • 5 Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium. Electronic address: [email protected] , (Belgium)
Type
Published Article
Journal
American Journal of Kidney Diseases
Publisher
Elsevier
Publication Date
Aug 01, 2020
Volume
76
Issue
2
Pages
288–291
Identifiers
DOI: 10.1053/j.ajkd.2019.08.032
PMID: 31810732
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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