HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

mTOR inhibitors and dyslipidemia in transplant recipients: a cause for concern?

Abstract
Post-transplant dyslipidemia is exacerbated by mammalian target of rapamycin (mTOR) inhibitors. Early clinical trials of mTOR inhibitors used fixed dosing with no concomitant reduction in calcineurin inhibitor (CNI) exposure, leading to concerns when consistent and marked dyslipidemia was observed. With use of modern concentration-controlled mTOR inhibitor regimens within CNI-free or reduced-exposure CNI regimens, however, the dyslipidemic effect persists but is less pronounced. Typically, total cholesterol levels are at the upper end of normal, or indicate borderline risk, in kidney and liver transplant recipients, and are lower in heart transplant patients under near-universal statin therapy. Of note, it is possible that mTOR inhibitors may offer a cardioprotective effect. Experimental evidence for delayed progression of atherosclerosis is consistent with evidence from heart transplantation that coronary artery intimal thickening and the incidence of cardiac allograft vasculopathy are reduced with everolimus versus cyclosporine therapy. Preliminary data also indicate that mTOR inhibitors may improve arterial stiffness, a predictor of cardiovascular events, and may reduce ventricular remodeling and decrease left ventricular mass through an anti-fibrotic effect. Post-transplant dyslipidemia under mTOR inhibitor therapy should be monitored and managed closely, but unless unresponsive to therapy should not be regarded as a barrier to its use.
AuthorsHallvard Holdaas, Luciano Potena, Faouzi Saliba
JournalTransplantation reviews (Orlando, Fla.) (Transplant Rev (Orlando)) Vol. 29 Issue 2 Pg. 93-102 (Apr 2015) ISSN: 1557-9816 [Electronic] United States
PMID25227328 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • TOR Serine-Threonine Kinases
Topics
  • Calcineurin Inhibitors (therapeutic use)
  • Cyclosporine (therapeutic use)
  • Dyslipidemias (etiology, prevention & control)
  • Everolimus (therapeutic use)
  • Graft Rejection (prevention & control)
  • Humans
  • Immunosuppressive Agents (therapeutic use)
  • Organ Transplantation (adverse effects)
  • TOR Serine-Threonine Kinases (antagonists & inhibitors)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: