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Updated: Mar 17, 2026
Murine Kidney Transplant Technique
Published on: October 20, 2015
Roles of mTOR complexes in the kidney: implications for renal disease and transplantation
Daniel Fantus1, Natasha M Rogers1,2, Florian Grahammer3
1Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, W1540 BST, Pittsburgh, Pennsylvania 15261, USA.
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.
Insights
The mechanistic target of rapamycin (mTOR) pathway regulates kidney cell growth and immunity. mTOR inhibitors show promise in kidney disease and transplantation but have toxicities, necessitating further research.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- The mechanistic target of rapamycin (mTOR) pathway is crucial for regulating cellular metabolism, growth, and proliferation.
- mTOR signaling, through mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), plays significant roles in maintaining podocyte homeostasis and tubular transport within the kidney.
- Dysregulation of the mTOR pathway is implicated in various kidney diseases, including renal injury, polycystic kidney disease, and glomerular diseases like diabetic nephropathy.
Purpose of the Study:
- To explore the multifaceted roles of the mTOR pathway in renal cell function and disease pathogenesis.
- To investigate the impact of mTOR targeting on immune cell homeostasis and function in the context of kidney transplantation and de novo renal diseases.
- To evaluate the clinical utility and limitations of mTOR inhibitors in renal transplantation, considering both graft outcomes and adverse effects.
Main Methods:
- Selective gene targeting of mTORC1 and mTORC2 in renal cell populations.
- Pharmacologic inhibition of the mTOR pathway.
- Analysis of clinical data from renal transplant recipients converted to mTOR inhibitors.
Main Results:
- mTOR pathway is integral to podocyte homeostasis and tubular transport.
- mTOR targeting influences immune responses relevant to renal allograft outcomes and de novo kidney diseases.
- Conversion to mTOR inhibitors in renal transplantation can achieve excellent long-term graft function, despite associated toxicities.
- mTOR inhibitors demonstrate unique benefits, including reduced rates of squamous cell carcinoma and cytomegalovirus infection.
Conclusions:
- The mTOR pathway is a key regulator in kidney physiology and pathology.
- Targeting mTOR offers therapeutic potential for various renal diseases and improving transplant outcomes.
- Understanding mTORC1 and mTORC2 mechanisms is vital for advancing clinical applications and mitigating toxicities associated with mTOR inhibitors.
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