m-TOR Inhibitors in Kidney Transplantation: A Comprehensive Review

Abstract

Mammalian target of rapamaycin inhibitors (mTOR-I) has been in use in kidney transplantation for over two decades. Since their introduction, they have been used in different combination immunosuppressant for low risk group renal transplantation. They have been in use in the various (Calcineurin inhibitors) CNI-free protocols, either as De novo regiments, or by conversion from CNIs at a later stage. Many of these studies reported comparable graft rejection rate and a better kidney function (eGFR) compared to standard CNI protocols. Also mTOR-I when used in combination with CNIs, facilitated the use of lower doses of CNIs with the resultant reduction of CNI related side effects, without seriously compromising graft outcome. They are of particular interest among certain group of renal transplant recipients, including those with malignancy, post-transplant encapsulating peritoneal scelorosis, CMV and BK virus infections. Moreover, protocols containing mTOR-I showed comparable results to standard protocols among recipients of kidneys from extended-criteria transplantation. However, only few reports studied their use in high risk group renal transplantation, with variable outcomes. There is a noticeable drop in their popularity in the recent years, and their use was associated with multiple adverse events, in addition to a recent concern of their link to increased mortality. Also, a high discontinuation rate was demonstrated across many of the studies available to date. More studies are still needed to clarify the above-mentioned concerns.