mTOR inhibitors in pancreas transplant: adverse effects and drug-drug interactions

Area of Science:

• Nephrology
• Transplantation Immunology
• Pharmacology

Background:

• Pancreas allograft survival has improved but remains challenged by rejection and immunosuppression toxicity.
• Long-term outcomes are affected by calcineurin inhibitor (CNI) nephrotoxicity and mammalian target of rapamycin inhibitor (mTORi) side effects.
• mTOR inhibitors (sirolimus/SRL, everolimus/EVR) are explored as alternatives to CNIs, particularly for kidney function preservation.

Purpose of the Study:

• To review the literature on mTOR inhibitors in pancreas transplantation.
• To summarize the nephrotoxic and diabetogenic mechanisms of mTOR inhibitors.
• To discuss alternatives and adverse events associated with mTOR inhibitors.

Main Methods:

• Literature review of existing research on mTOR inhibitors.
• Analysis of drug-drug interactions, nephrotoxicity, and diabetogenicity.
• Evaluation of clinical studies and experimental data.

Main Results:

• Switching from CNIs to mTORi, especially everolimus, may preserve kidney function post-pancreas transplant.
• Long-term mTORi use can lead to proteinuria and hyperglycemia by disrupting cellular processes like autophagy and downregulating VEGF.
• Adverse events and drug-drug interactions of mTORi require careful management.

Conclusions:

• CNI-based regimens are standard, but mTORi offer a potential alternative for kidney preservation.
• Understanding mTORi mechanisms is vital for managing side effects like proteinuria and hyperglycemia.
• Minimizing mTORi side effects may improve kidney allograft survival; further studies are needed for pancreas allograft impact.