title: Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: calcineurin-inhibitors conversion or minimization?
abstract: BACKGROUND
  In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i.
  
  
  METHODS
  In a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR<60 mL/min/1.73 m(2)), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences.
  
  
  RESULTS
  Overall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p=0.07).
  
  
  CONCLUSIONS
  In terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk.
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Marques de Valdecilla, Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain. Electronic address: cargvf@gmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Gonzalez-Vilchez
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Marques de Valdecilla, Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Vazquez de Prada
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital de La Coruña, La Coruña, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Paniagua
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Puerta de Hierro, Majadahonda, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Gomez-Bueno
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Reina Sofia, Cordoba, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Arizon
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital La Fe, Valencia, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Almenar
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Roig
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital 12 de Octubre, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Delgado
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Central de Asturias, Oviedo, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Lambert
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Clinic de Barcelona, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Perez-Villa
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Miguel Servet, Zaragoza, Spain.
authors.forename: M L
authors.initials: ML
authors.lastname: Sanz-Julve
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital de La Coruña, La Coruña, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Crespo-Leiro
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Puerta de Hierro, Majadahonda, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Segovia
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Reina Sofia, Cordoba, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Lopez-Granados
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital La Fe, Valencia, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Martinez-Dolz
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Mirabet
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital 12 de Octubre, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Escribano
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Central de Asturias, Oviedo, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Diaz-Molina
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Clinic de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Farrero
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Miguel Servet, Zaragoza, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Blasco
mesh_terms: D000368:Aged; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D015331:Cohort Studies; D057915:Drug Substitution / Q000639:trends; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000639:trends; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D012189:Retrospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D019703:Calcineurin; D020123:Sirolimus
keywords: Cardiac transplantation; Everolimus; Immunosuppression; Renal function; Sirolimus