title: Clinical evidence on the use of anti-mTOR drugs in renal transplantation.
abstract: Calcineurin inhibitor drugs (CNI) are the mainstay of modern immunosuppression in renal transplantation. However, they contribute significantly to the chronic loss of renal grafts and the high morbidity and mortality in this population due to their deleterious effects on the renal graft, cardiovascular profile and tumour pathology. Anti-mTOR drugs, sirolimus (SRL) and everolimus (EVE) are potent immunosuppressants with antiproliferative and anti-migratory capacities. These properties mean that they have a potential protective role in graft dysfunction, in renal function optimisation and the appearance of malignant tumours. Indeed, clinical trials and observational studies have demonstrated that conversion from CNI to anti-mTOR-based maintenance therapy has beneficial effects on transplant outcomes in terms of renal function, without significant increase in acute rejection rates. This review article examines the evidence of the use of anti-mTOR in the following clinical situations following renal transplantation: 1) prevention of immune dysfunction and renal function preservation in de novo renal transplantation and after early or late CNI withdrawal; 2) chronic dysfunction of the renal graft; 3) cardiovascular effects; 4) de novo post-transplant diabetes, and 5) de novo tumour pathology.
authors.affiliation: Nephrology Department, Carlos Haya Regional Hospital, Malaga. Spain. domingohernandez@gmail.com
authors.forename: D
authors.initials: D
authors.lastname: Hernández
authors.forename: D
authors.initials: D
authors.lastname: Martínez
authors.forename: E
authors.initials: E
authors.lastname: Gutiérrez
authors.forename: V
authors.initials: V
authors.lastname: López
authors.forename: C
authors.initials: C
authors.lastname: Gutiérrez
authors.forename: P
authors.initials: P
authors.lastname: García
authors.forename: C
authors.initials: C
authors.lastname: Cobelo
authors.forename: M
authors.initials: M
authors.lastname: Cabello
authors.forename: D
authors.initials: D
authors.lastname: Burgos
authors.forename: E
authors.initials: E
authors.lastname: Sola
authors.forename: M
authors.initials: M
authors.lastname: González-Molina
mesh_terms: D000818:Animals; D065095:Calcineurin Inhibitors; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced; D050171:Dyslipidemias / Q000139:chemically induced; D000068338:Everolimus; D019317:Evidence-Based Medicine; D006084:Graft Rejection / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology*; D023421:Models, Animal; D015337:Multicenter Studies as Topic; D009369:Neoplasms / Q000517:prevention & control; D011183:Postoperative Complications / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / 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