title: Efficacy of mycophenolate mofetil combined with very low-dose cyclosporine microemulsion in long-term liver-transplant patients with renal dysfunction.
abstract: BACKGROUND
  Cyclosporine (CsA)-induced renal dysfunction is common after liver transplantation. We evaluated the efficacy of tapering CsA to a very low dose and introducing mycophenolate mofetil (MMF) in long-term liver-transplant recipients with renal dysfunction. In addition, we assessed the impact of this strategy on calcineurin inhibition and on transforming growth factor (TGF)-beta levels.
  
  
  METHODS
  We prospectively enrolled 19 adult, long-term (>1 year) liver-transplant recipients with a decreased creatinine clearance greater than 25% compared with the first month posttransplant. MMF was introduced, and CsA was tapered to 25 mg twice daily. Calcineurin inhibition and TGF-beta were measured at baseline and 3 months thereafter.
  
  
  RESULTS
  The CsA dose was tapered over 13+/-3 weeks. At 1-year follow-up, serum creatinine decreased from 141+/-24 to 105+/-22 micromol/L (P=0.002), creatinine clearance increased from 53+/-9 to 71+/-19 ml/min (P=0.02), and glomerular filtration rate increased from 40+/-13 to 64+/-18 mL/min (P=0.002). The incidence of acute rejection was 29%. Antihypertensive medications were discontinued in 71% of the patients. Although CsA levels decreased significantly, serum TGF-beta did not differ from normal controls, and calcineurin inhibition remained stable. The incidence of gastrointestinal side-effects and leukopenia was 18% and 24%, respectively.
  
  
  CONCLUSIONS
  In long-term liver-transplant recipients with renal dysfunction, the introduction of MMF followed by tapering of CsA to a very low dose resulted in a significant improvement in renal function. However, this strategy maybe associated with a risk of acute rejection. The clinical pertinence of measuring serum TGF-beta levels and calcineurin inhibition remains to be determined.
authors.affiliation: Department of Medicine, Royal Victoria Hospital, McGill University Health Center, Montréal, Québec, Canada.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cantarovich
authors.forename: George N
authors.initials: GN
authors.lastname: Tzimas
authors.forename: J
authors.initials: J
authors.lastname: Barkun
authors.forename: M
authors.initials: M
authors.lastname: Deschênes
authors.forename: E
authors.initials: E
authors.lastname: Alpert
authors.forename: J
authors.initials: J
authors.lastname: Tchervenkov
mesh_terms: D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004655:Emulsions; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007677:Kidney Function Tests; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid