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mTOR inhibitor/proliferation signal inhibitors: entering or leaving the field?

Lionel Rostaing1, Nassim Kamar

  • 1Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Toulouse. rostaing.l@chu-toulouse.fr

Journal of Nephrology
|February 16, 2010
PubMed
Abstract

Insights

Mammalian target of rapamycin inhibitors (mTOR-Is) offer benefits in kidney transplantation, reducing cancer risk and nephrotoxicity compared to calcineurin inhibitors (CNIs). Early use after 3 months post-transplant is safe and effective.

Area of Science:

  • Immunology
  • Pharmacology
  • Nephrology

Background:

  • The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and metabolism.
  • mTOR inhibitors (mTOR-Is) like sirolimus and everolimus induce antiproliferative effects.

Purpose of the Study:

  • To review studies on mTOR-Is utilization in kidney transplant patients.
  • To evaluate the outcomes associated with mTOR-Is in kidney transplantation.

Main Methods:

  • Systematic review of major studies on mTOR-Is in kidney transplant (KT) recipients.
  • Analysis of outcomes including immunosuppression strategies and adverse events.

Main Results:

  • Sirolimus-based immunosuppression without calcineurin inhibitors (CNIs) in de novo KT patients showed worse outcomes.
  • mTOR-Is are safe and effective when used with CNI minimization or CNI-free protocols after 3 months post-transplant.
  • mTOR-Is reduced de novo malignancies and improved outcomes for Kaposi's sarcoma and skin cancers.

Conclusions:

  • mTOR-Is demonstrate potential for wider use in kidney transplant patients.
  • Reduced nephrotoxicity and lower incidence of de novo cancers compared to CNIs support increased use of mTOR-Is.

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