title: Mycophenolate mofetil dose reduction and the risk of acute rejection after renal transplantation.
abstract: Mycophenolate mofetil (MMF) significantly decreases acute rejection rates after renal transplantation, but intolerance often occurs, leading to dose reduction. The clinical effect of MMF dose reduction has not been clearly established. This study determined whether MMF dose reduction after renal transplantation was associated with subsequent risk of acute rejection. This retrospective cohort study assessed 213 renal transplant recipients. Cox regression was used to model MMF dose as a time-dependent variable, with time to first acute rejection as the primary outcome. One hundred twenty-six patients (59%) had a total of 176 MMF dose reductions during the study. MMF dose was reduced because of leukopenia (55.1%), gastrointestinal symptoms (22.2%), infection (7.4%), malignancy (1.1%), and unknown reasons (14.2%). The cumulative number of days with the MMF dose reduced below full dose was an independent predictor of acute rejection. The relative risk of rejection increased by 4% for every week that the MMF dose was reduced below full dose. No significant association was observed between the number of days with MMF dropped below full dose and allograft failure. The cumulative number of days with the MMF dose dropped below full dose is a significant predictor of acute rejection after renal transplantation. Clinicians need to be aware of the rejection risk when the MMF dose is reduced and maintain close surveillance on such patients.
authors.affiliation: Division of Nephrology, Kidney Research Centre, and Department of Medicine, University of Ottawa, and Clinical Epidemiology Unit, Ottawa Health Research Institute, Ottawa, Ontario, Canada. gknoll@ottawahospital.on.ca
authors.forename: Greg A
authors.initials: GA
authors.lastname: Knoll
authors.forename: Ian
authors.initials: I
authors.lastname: MacDonald
authors.forename: Asmat
authors.initials: A
authors.lastname: Khan
authors.forename: Carl
authors.initials: C
authors.lastname: Van Walraven
mesh_terms: D000208:Acute Disease; D000328:Adult; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects* / Q000031:analogs & derivatives*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid