Progressive decline in allograft function and cardiovascular mortality after kidney transplantation remain major clinical challenges that can potentially be addressed by the mammalian target of rapamycin (mTOR) inhibitors, everolimus and sirolimus. mTOR inhibitors maintain immunosuppressive efficacy after minimization of calcineurin inhibitor (CNI) therapy and can achieve significant long-term improvements in renal function. Recently, data have accumulated that suggest mTOR inhibitors may offer

more »

... cardioprotective effects. In animal models, inhibition of mTOR leads to regression of cardiac hypertrophy, and the limited data consistently point to a remodeling benefit following heart transplantation. Experimentally, mTOR inhibitors restrict atherogenesis, confirmed clinically by intravascular ultrasound data demonstrating lower rates of transplant vasculopathy in heart transplant recipients on everolimus. Lastly, mTOR inhibitors appear to ameliorate arterial stiffness, a known risk factor for post-transplant cardiovascular events, but data remain sparse. The ELEVATE study will examine the renal effect of early conversion from CNI therapy to everolimus after kidney transplantation. Key secondary endpoints include the change in left ventricular mass index, the first time this endpoint has been included in a prospective study of an mTOR inhibitor. The occurrence of cardiovascular events will be rigorously documented and pulse wave velocity is being measured in a subpopulation of patients. Results from this innovative trial are awaited with interest.