Mammalian target of rapamycin inhibitors: A paradigm shift in current immunosuppression protocols

Abstract

Immunosuppression is an obligate necessity in kidney transplant. However, the standard immunosuppression causes chronic deterioration of allograft function over long term use. Mammalian target of rapamycin (mTOR) inhibitors provide an alternative in such scenario. The mTOR inhibitors engage FKBP12 to create complexes that engage and inhibit the target of rapamycin. Inhibition of the TOR blocks signal 3 by preventing cytokine receptors from activating the cell cycle. mTOR inhibitors are associated with less viral infection and disease in kidney transplants and also beneficial in post-transplant malignancy. There are various strategies of using mTOR inhibitors either as upfront de novo therapy or later on as switch over therapy. They can also be used in cases of complications arising from standard immunosuppression. mTOR inhibitors also have adverse effects which can be managed by dose reduction but may require stoppage in case of serious complications. Surgical issues need to be kept in mind in view of delayed wound healing. mTOR inhibitors add on to the armamentarium of the available immunosuppression and can give excellent results with judicious use. The present review aims to provide updated information regarding the use of these drugs in post-renal transplantation setting.

Keywords

• Renal transplantation
• Chronic allograft nephropathy
• mTOR inhibitors