title: Long-term effects of calcineurin inhibitor conversion to mycophenolate mofetil on renal function after liver transplantation.
abstract: Calcineurin inhibitors (CNIs) are the cornerstone of immunosuppression after liver transplantation. However, CNI treatment is frequently associated with chronic renal failure (CRF). The reduction or interruption of CNI may reduce renal failure. We prospectively studied 49 liver recipients treated with CNI (tacrolimus, n = 14; cyclosporine, n = 35) who secondarily developed CNI-associated CRF and for whom mycophenolate mofetil (MMF) was introduced to reduce or withdraw CNI. The creatinine clearance (CCl; 42.9 +/- 14 ml/minute) increased significantly after CNI reduction (48.8 +/- 17 ml/minute after 1 year, 49.9 +/- 18 ml/minute after 2 years, and 58.4 +/- 20 ml/minute after 3 years, P < 0.0001). CCl decreased during the 2 years before CNI reduction at a rate of -5.6 +/- 5 ml/minute/year; for the 2 years after CNI reduction, CCl increased significantly by +3.2 +/- 4.3 ml/minute/year (P < 0.0001). Ten patients did not have improved renal function after 1 year, but the rate of decrease in CCl slowed after CNI reduction. Three parameters were identified as risk factors for unresponsiveness to CNI reduction: (1) low CCl at MMF introduction, (2) a high rate of CCl decrease during the 2 years before conversion, and (3) alcoholic cirrhosis. The type of CNI molecule used did not impair the renal response. None of the patients developed acute or chronic graft rejection after the reduction or interruption of CNI. In liver recipients with CRF, a reduction or withdrawal of CNI concomitantly with the introduction of MMF was safe and was associated with an improvement in renal function.
authors.affiliation: Nephrology and Transplantation Unit, Kremlin Bicêtre Hospital, Kremlin Bicêtre France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Créput
authors.forename: Frederique
authors.initials: F
authors.lastname: Blandin
authors.forename: Benjamin
authors.initials: B
authors.lastname: Deroure
authors.forename: Bruno
authors.initials: B
authors.lastname: Roche
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.forename: Bernard
authors.initials: B
authors.lastname: Charpentier
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000517:prevention & control; D007677:Kidney Function Tests; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid