title: Acute rejection in low-toxicity regimens: clinical impact and risk factors in the Symphony study.
abstract: The Symphony study assessed whether mycophenolate mofetil (MMF)-based regimens containing reduced doses of adjunct immunosuppressants could reduce toxicity while maintaining efficacy. Here, we examined the impact of acute rejection and associated risk factors. The incidence of biopsy-proven acute rejection in the low-dose tacrolimus group was approximately half that of the standard-dose cyclosporine and low-dose cyclosporine groups, and a third of that in the low-dose sirolimus group. The low-dose cyclosporine group had more severe rejection episodes (≥grade II) compared with other groups. Acute rejection was associated with a 10 mL/min glomerular filtration rate (GFR) reduction and a 5.3% absolute increase in graft loss at 12 months. Overall, the highest GFR was found in both rejecters and non-rejecters receiving low-dose tacrolimus, both in an intent-to-treat analysis and in patients successfully treated according to the protocol. In Cox regression models, human leukocyte antigen (HLA) mismatches and expanded criteria donors increased the acute rejection risk, while recipient age, living related donor, and MMF dose were associated with a reduced risk. Acute rejection was associated with worse outcome but did not entirely explain the differences among the treatment groups. The 2 g MMF plus low-dose tacrolimus combination appears to be the most efficient of all regimens examined regardless of acute rejection.
authors.affiliation: Department of Nephrology and Medical Intensive Care, Charité, Virchow-Klinikum, Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Frei
authors.forename: Pierre
authors.initials: P
authors.lastname: Daloze
authors.forename: Stefan
authors.initials: S
authors.lastname: Vítko
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klempnauer
authors.forename: Rafael
authors.initials: R
authors.lastname: Reyes-Acevedo
authors.forename: Izzet
authors.initials: I
authors.lastname: Titiz
authors.forename: Lutz
authors.initials: L
authors.lastname: Fricke
authors.forename: Corrado
authors.initials: C
authors.lastname: Bernasconi
authors.forename: Henrik
authors.initials: H
authors.lastname: Ekberg
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D012307:Risk Factors; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus