title: Roles of mTOR complexes in the kidney: implications for renal disease and transplantation.
abstract: The mTOR pathway has a central role in the regulation of cell metabolism, growth and proliferation. Studies involving selective gene targeting of mTOR complexes (mTORC1 and mTORC2) in renal cell populations and/or pharmacologic mTOR inhibition have revealed important roles of mTOR in podocyte homeostasis and tubular transport. Important advances have also been made in understanding the role of mTOR in renal injury, polycystic kidney disease and glomerular diseases, including diabetic nephropathy. Novel insights into the roles of mTORC1 and mTORC2 in the regulation of immune cell homeostasis and function are helping to improve understanding of the complex effects of mTOR targeting on immune responses, including those that impact both de novo renal disease and renal allograft outcomes. Extensive experience in clinical renal transplantation has resulted in successful conversion of patients from calcineurin inhibitors to mTOR inhibitors at various times post-transplantation, with excellent long-term graft function. Widespread use of this practice has, however, been limited owing to mTOR-inhibitor- related toxicities. Unique attributes of mTOR inhibitors include reduced rates of squamous cell carcinoma and cytomegalovirus infection compared to other regimens. As understanding of the mechanisms by which mTORC1 and mTORC2 drive the pathogenesis of renal disease progresses, clinical studies of mTOR pathway targeting will enable testing of evolving hypotheses.
authors.affiliation: Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, W1540 BST, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fantus
authors.affiliation: Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, W1540 BST, Pittsburgh, Pennsylvania 15261, USA.|Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Rogers
authors.affiliation: Department of Medicine IV, Medical Center-Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, Freiburg 79106, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Grahammer
authors.affiliation: Department of Medicine IV, Medical Center-Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, Freiburg 79106, Germany.|BIOSS Center for Biological Signalling Studies, University of Freiburg, Schänzlestrasse 18, 79104 Freiburg, Germany.
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Huber
authors.affiliation: Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, W1540 BST, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Angus W
authors.initials: AW
authors.lastname: Thomson
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D005355:Fibrosis / Q000209:etiology; D006084:Graft Rejection / Q000209:etiology; D006801:Humans; D007511:Ischemia / Q000209:etiology; D007668:Kidney / Q000098:blood supply / Q000166:cytology / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology*; D007678:Kidney Glomerulus; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000166:cytology; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000502:physiology*; D050199:Podocytes / Q000502:physiology; D007690:Polycystic Kidney Diseases / Q000209:etiology; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases