PMID- 25227328
OWN - NLM
STAT- MEDLINE
DCOM- 20160115
LR  - 20211203
IS  - 1557-9816 (Electronic)
IS  - 0955-470X (Linking)
VI  - 29
IP  - 2
DP  - 2015 Apr
TI  - mTOR inhibitors and dyslipidemia in transplant recipients: a cause for concern?
PG  - 93-102
LID - S0955-470X(14)00059-7 [pii]
LID - 10.1016/j.trre.2014.08.003 [doi]
AB  - 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.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Holdaas, Hallvard
AU  - Holdaas H
AD  - Section of Nephrology, Department of Transplant Medicine, Oslo University 
      Hospital, Rikshospitalet, Oslo, Norway. Electronic address: 
      hallvard.holdaas@rikshospitalet.no.
FAU - Potena, Luciano
AU  - Potena L
AD  - Heart Failure and Heart Transplant Program, Academic Hospital S. Orsola-Malpighi, 
      Alma-Mater University of Bologna, Bologna, Italy.
FAU - Saliba, Faouzi
AU  - Saliba F
AD  - AP-HP Hopital Paul Brousse, Centre Hepato-Biliaire, Villejuif, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20140827
PL  - United States
TA  - Transplant Rev (Orlando)
JT  - Transplantation reviews (Orlando, Fla.)
JID - 8804364
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Calcineurin Inhibitors/therapeutic use
MH  - Cyclosporine/therapeutic use
MH  - Dyslipidemias/*etiology/prevention & control
MH  - Everolimus/*therapeutic use
MH  - Graft Rejection/prevention & control
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Organ Transplantation/*adverse effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
EDAT- 2014/09/18 06:00
MHDA- 2016/01/16 06:00
CRDT- 2014/09/18 06:00
PHST- 2014/01/22 00:00 [received]
PHST- 2014/07/19 00:00 [revised]
PHST- 2014/08/22 00:00 [accepted]
PHST- 2014/09/18 06:00 [entrez]
PHST- 2014/09/18 06:00 [pubmed]
PHST- 2016/01/16 06:00 [medline]
AID - S0955-470X(14)00059-7 [pii]
AID - 10.1016/j.trre.2014.08.003 [doi]
PST - ppublish
SO  - Transplant Rev (Orlando). 2015 Apr;29(2):93-102. doi: 10.1016/j.trre.2014.08.003. 
      Epub 2014 Aug 27.