title: Conversion to mycophenolate mofetil monotherapy in liver recipients: Calcineurin inhibitor levels are key.
abstract: The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow-up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.
authors.affiliation: Departamentos de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile.
authors.forename: Blanca
authors.initials: B
authors.lastname: Norero
authors.affiliation: Departamentos de Gastroenterología y Nutrición Pediátrica, Escuela de Medicina, Pontificia Universidad Católica de Chile.
authors.forename: Carolina A
authors.initials: CA
authors.lastname: Serrano
authors.affiliation: Institute of Liver Studies, MRC Centre for Transplantation, King's College London, London SE5 9RS, United Kingdom.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sanchez-Fueyo
authors.affiliation: Patología y Escuela de Medicina, Pontificia Universidad Católica de Chile.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Duarte
authors.affiliation: Patología y Escuela de Medicina, Pontificia Universidad Católica de Chile.
authors.forename: Javiera
authors.initials: J
authors.lastname: Torres
authors.affiliation: Hemato-Oncología, Escuela de Medicina, Pontificia Universidad Católica de Chile.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Ocquetau
authors.forename: Francisco
authors.initials: F
authors.lastname: Barrera
authors.affiliation: Departamentos de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile.
authors.forename: Marco
authors.initials: M
authors.lastname: Arrese
authors.affiliation: Departamentos de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Soza
authors.affiliation: Departamentos de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Benítez
mesh_terms: D000368:Aged; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016009:Chi-Square Distribution; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D051858:Forkhead Transcription Factors / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus