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.