title: Mycophenolate mofetil dose reduction for gastrointestinal intolerance is associated with increased rates of rejection in heart transplant patients.
abstract: BACKGROUND
  Gastrointestinal (GI) intolerance to mycophenolate mofetil (MMF) is a frequent problem. We conducted a retrospective analysis of all the heart transplant patients followed up at the Toronto General Hospital from the years 1999 to 2006 to determine the impact of dose reductions for GI intolerance on rejection rates.
  
  
  METHODS
  The charts of all patients followed up in the heart transplant clinic at the Toronto General Hospital from the years 1999 to 2006 were reviewed. Sustained significant rejection was defined as an International Society of Heart and Lung Transplantation grade 2 or higher on 2 successive biopsies. The Student's t-test was used to compare rates of rejection between populations.
  
  
  RESULTS
  Mycophenolate mofetil was part of the anti-rejection regimen in 182 of 189 patients (98%), and the medication dose in 71% of these patients had to be reduced at some point because of intolerance or toxicity. The prevalence of sustained significant rejection was significantly higher in the group of patients with GI intolerance to MMF compared with patients maintained on target doses (66% vs 35%, p = 0.002) or patients with non-GI related toxicities necessitating dose reduction (67% vs 35%, p = 0.003).
  
  
  CONCLUSIONS
  Gastrointestinal intolerance is a common reason for MMF dose reduction in heart transplant patients and was associated with a significantly increased rate of sustained rejection, suggesting that these individuals need to have particularly close follow-up.
authors.affiliation: Division of Cardiology, Toronto General Hospital, Toronto, Ontario, Canada. pgaliwango@utoronto.ca
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Galiwango
authors.forename: Diego H
authors.initials: DH
authors.lastname: Delgado
authors.forename: Raymond
authors.initials: R
authors.lastname: Yan
authors.forename: Stella
authors.initials: S
authors.lastname: Kozuszko
authors.forename: Robert
authors.initials: R
authors.lastname: Smith
authors.forename: Vivek
authors.initials: V
authors.lastname: Rao
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ross
mesh_terms: D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006084:Graft Rejection / Q000188:drug therapy* / Q000453:epidemiology*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009864:Ontario / Q000453:epidemiology; D011355:Prodrugs; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents; D011355:Prodrugs; D009173:Mycophenolic Acid