title: The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation.
abstract: BACKGROUND
  Mycophenolate mofetil (MMF) has proven to be a very effective drug for the prevention of acute rejection following renal transplantation when dosed as prescribed at 2 or 3 g/d. However, circumstances arise in clinical transplantation where the dose must be lowered, either to avoid drug toxicity or because of concurrent infection. The impact on the incidence of acute rejection and graft survival when the MMF dose must be lowered has not previously been investigated.
  
  
  METHODS
  In this study, a cohort of 721 kidney transplant recipients who received immunosuppression using MMF in conjunction with cyclosporine and prednisone and OKT3 (n = 425) or Simulect (n = 296) induction were evaluated. Clinical outcomes were compared and contrasted between patients with and without MMF dose changes within the first year post-transplantation.
  
  
  RESULTS
  The majority of patients (70.3%, n = 507) had at least one dose change within the first post-transplant year. Compared with the 214 patients who did not have a dose change, these patients had a much higher incidence of acute rejection within the first post-transplant year (23.3% vs. 3.7%, p < 0.001). This resulted in a significantly decreased 3-yr death-censored graft survival (76.3% vs. 88.3%, p = 0.003). The incidence of acute rejection for patients who had a dose change was highest if the dose change occurred within the first post-transplant month (34.4%). The incidence of acute rejection for the dose change patients was influenced by recipient ethnicity (African-American vs. Caucasian) and the type of induction agent used (OKT3 vs. Simulect).
  
  
  CONCLUSIONS
  Altering the dose of MMF within the first post-transplant year correlated with a significantly worse clinical outcome in this cohort of renal transplant recipients. These data suggest that avoidance of MMF dose changes within the first year after renal transplantation would result in improved graft survival.
authors.affiliation: Division of Transplantation, Department of General Surgery, The Ohio State University Medical Center, Columbus, OH, USA. pelletier-1@medctr.osu.edu
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Pelletier
authors.forename: Baris
authors.initials: B
authors.lastname: Akin
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Henry
authors.forename: Ginny L
authors.initials: GL
authors.lastname: Bumgardner
authors.forename: Elmahdi A
authors.initials: EA
authors.lastname: Elkhammas
authors.forename: Amer
authors.initials: A
authors.lastname: Rajab
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Ferguson
mesh_terms: D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015994:Incidence; D016030:Kidney Transplantation; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000627:therapeutic use; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000627:therapeutic use; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone