title: Systematic Review on Role of Mammalian Target of Rapamycin Inhibitors as an Alternative to Calcineurin Inhibitors in Renal Transplant: Challenges and Window to Excel.
abstract: OBJECTIVE
  This review focuses on the current limited evidence of graft function and graft survival in various immunosuppressive regimens involving mammalian target of rapamycin inhibitors with or without calcineurin inhibitors.
  
  
  METHODS
  We evaluated the current literature for describing the role of mammalian target of rapamycin inhibitors as an alternative to calcineurin inhibitors by searching the PubMed, EMBASE, Cochrane, Crossref, and Scopus databases using medical subject heading terms.
  
  
  RESULTS
  Our detailed analyses of all relevant literature showed use of mammalian target of rapamycin inhibitor-based de novo regimens, early calcineurin inhibitor withdrawal with subsequent introduction of mammalian target of rapamycin inhibitor-based regimens, and late conversion from a calcineurin inhibitor-based regimen to mammalian target of rapamycin inhibitor-based regimens. Notably, early calcineurin inhibitor withdrawal with subsequent introduction of mammalian target of rapamycin inhibitor-based regimen seemed to be a more practical and realistic approach toward immunosuppressive treatment of renal transplant recipients. However, in view of the high rejection rate observed in these studies, it is advisable not to offer these regimens to patients with moderate to high immunologic risk.
  
  
  CONCLUSIONS
  The present evidences suggest that treatment with mammalian target of rapamycin inhibitors allows early and substantial calcineurin inhibitor minimization. The mammalian target of rapamycin inhibitors everolimus and sirolimus are preferred due to their complementary mechanisms of action and favorable nephrotoxicity profile, which have opened the way for calcineurin inhibitor reduction/withdrawal in the early posttransplant period.
authors.affiliation: From the Department of Hepato-Pancreato-Biliary Surgery, Hammersmith Hospital, Imperial College, London, United Kingdom; and the Faculty of Health and Sciences, Institute of Learning and Teaching, University of Liverpool, United Kingdom.
authors.forename: Jayant
authors.initials: J
authors.lastname: Kumar
authors.forename: Julie M
authors.initials: JM
authors.lastname: Bridson
authors.forename: Ajay
authors.initials: A
authors.lastname: Sharma
authors.forename: Ahmed
authors.initials: A
authors.lastname: Halawa
mesh_terms: D065095:Calcineurin Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases