title: Safety of mTOR inhibitors in adult solid organ transplantation.
abstract: BACKGROUND
  Mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) are a class of immunosuppressive drugs approved for solid organ transplantation (SOT). By inhibiting the ubiquitous mTOR pathway, they present a peculiar safety profile. The increased incidence of serious adverse events in early studies halted the enthusiasm as a kidney sparing alternative to calcineurin inhibitors (CNI).
  
  
  METHODS
  Herein we review mTOR inhibitors safety profile for adult organ transplantation, ranging from acute side effects, such as lymphoceles, delayed wound healing, or cytopenias, to long-term ones which increase morbidity and mortality, such as cancer risk and metabolic profile. Infection, proteinuria, and cutaneous safety profiles are also addressed.
  
  
  CONCLUSIONS
  In the authors' opinion, mTOR inhibitors are a safe alternative to standard immunosuppression therapy with CNI and mycophenolate/azathioprine. Mild adverse events can be easily managed with an increased awareness and close monitoring of trough levels. Most serious side effects are dose- and organ-dependent. In kidney and heart transplantation mTOR inhibitors may be safely used as either low-dose de novo or through early-conversion. In the liver, conversion 4 weeks post-transplantation may reduce long-term chronic kidney disease secondary to calcineurin nephrotoxicity, without increasing hepatic artery/portal vein thrombosis.
authors.affiliation: a Department of Nephrology and Renal Transplantation , Hospital Clínic , Villarroel, 170, E-08036 Barcelona , Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Ventura-Aguiar
authors.affiliation: a Department of Nephrology and Renal Transplantation , Hospital Clínic , Villarroel, 170, E-08036 Barcelona , Spain.|b August Pi i Sunyer Biomedical Research Institute (IDIBAPS) , University of Barcelona , Barcelona , Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Campistol
authors.affiliation: a Department of Nephrology and Renal Transplantation , Hospital Clínic , Villarroel, 170, E-08036 Barcelona , Spain.
authors.forename: Fritz
authors.initials: F
authors.lastname: Diekmann
mesh_terms: D000328:Adult; D000818:Animals; D065095:Calcineurin Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D000068338:Everolimus / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D016377:Organ Transplantation / Q000379:methods*; D020123:Sirolimus / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Everolimus; NODAT; mTOR inhibitor; rapamycin; sirolimus; solid organ transplant