title: Mycophenolate mofetil tolerability and dose changes in tacrolimus-treated renal allograft recipients.
abstract: Mycophenolate mofetil (MMF) reduces acute rejection episodes (AREs) and may be associated with better renal graft survival than azathioprine. However, MMF-related adverse events are frequent; dose reduction or even withdrawal are quite common. Between 1999 and 2003, 115 renal transplantation patients were treated with tacrolimus, MMF, and steroids. An observational study was undertaken until graft loss (n = 7), death with a functioning graft (n = 2), or October 31, 2005 (mean follow-up-50 months). We assessed MMF dose reductions due to adverse events with the possible consequences on AREs and graft function. Treated acute ARE occurred in 11.3% of recipients, all of which were steroid-responsive. The median MMF initial daily dose was 1000 mg. In 44 patients (38.3%), the MMF dose was not changed; in 48 (41.7%) it was reduced; and in 23 (20%), withdrawn. The causes for dose modification were diarrhea (n = 33, 28.7% of all patients), leukopenia (n = 22, 19.1%), both of these (n = 7, 6.1%), or other events (n = 9, 7.8%). No AREs were attributed to MMF dose changes. Tacrolimus blood levels were higher at 3 years and serum creatinine values at 4 years among patients with dose changes (8.43 +/- 2.42 vs 7.37 +/- 2.23 ng/mL; P = .051 and 1.75 +/- 0.71 vs 1.48 +/- 0.38 mg/dL; P = .038, respectively). The need for MMF dose reduction or withdrawal was frequent in our patients with diarrhea or leukopenia during treatment with tacrolimus, MMF, and steroids. These adverse event-related changes were not associated with AREs, but produced deleterious effects on long-term graft function.
authors.affiliation: Servicios de Nefrología, Hospital Ramón y Cajal, Madrid, Spain. jpascual.hrc@salud.madrid.org
authors.forename: J
authors.initials: J
authors.lastname: Pascual
authors.forename: J
authors.initials: J
authors.lastname: Ocaña
authors.forename: R
authors.initials: R
authors.lastname: Marcén
authors.forename: A
authors.initials: A
authors.lastname: Fernández
authors.forename: C
authors.initials: C
authors.lastname: Galeano
authors.forename: M C
authors.initials: MC
authors.lastname: Alarcón
authors.forename: F J
authors.initials: FJ
authors.lastname: Burgos
authors.forename: J J
authors.initials: JJ
authors.lastname: Villafruela
authors.forename: J
authors.initials: J
authors.lastname: Ortuño
mesh_terms: D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D012086:Reoperation / Q000706:statistics & numerical data; D012189:Retrospective Studies; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; D009173:Mycophenolic Acid; D016559:Tacrolimus