title: Sirolimus conversion after liver transplantation: improvement in measured glomerular filtration rate after 2 years.
abstract: METHODS
  We reviewed our prospectively maintained database of 2005 liver transplantations. Therapy was either started de novo or converted from calcineurin inhibitors (CNIs) to sirolimus as the main immunosuppressive agent for nephrotoxicity or rejection. Glomerular filtration rate (GFR) was determined with iodine 125-labeled sodium isthalamate (Glofil-125), and serum creatinine concentration was obtained before and 3 months after transplantation, and yearly in both groups. Sirolimus levels were 10 to 15 ng/mL in patients at less than 3 months after transplantations and 5 to 10 ng/mL in the remaining patients. All patients received mycophenolate mofetil as maintenance therapy.
  
  
  RESULTS
  Data for 29 patients in the de novo group and 35 in the conversion group were reviewed. Patients in the de novo group demonstrated an acute cellular rejection rate of 17.2%, 40% of which were steroid resistant. In this group, 48.2% discontinuation of sirolimus was necessary because of adverse effects. Patients in the conversion group demonstrated an acute cellular rejection rate of 2.8% and a 34.3% rate of sirolimus discontinuation. Seventeen (56.7%) patients at 1 year and 8 (44.4%) patients at 2 years demonstrated continued improvement in GFR. In the conversion group, case-control analysis did not demonstrate a significant difference in GFR and serum creatinine concentration (P > .05) at 1 and 2 years after conversion. At the time of review, no patients in the conversion group required hemodialysis.
  
  
  CONCLUSIONS
  Conversion to sirolimus therapy is an effective strategy in improving renal function in patients with CNI-induced nephrotoxicity and can be done without increased rejection. Most of our patients (65.7%) tolerated sirolimus conversion. Of these, 56.7% and 44.4% demonstrated continued increase in GFR with the CNI-free regimen at 1 and 2 years, respectively. Long-term, large-population, prospective, randomized, controlled studies should further validate these results.
authors.affiliation: Transplantation Services, Baylor University Medical Center, Dallas, Texas 75246, USA. edmunds@baylorhealth.edu
authors.forename: E Q
authors.initials: EQ
authors.lastname: Sanchez
authors.forename: A P
authors.initials: AP
authors.lastname: Martin
authors.forename: T
authors.initials: T
authors.lastname: Ikegami
authors.forename: T
authors.initials: T
authors.lastname: Uemura
authors.forename: G
authors.initials: G
authors.lastname: Narasimhan
authors.forename: R M
authors.initials: RM
authors.lastname: Goldstein
authors.forename: M F
authors.initials: MF
authors.lastname: Levy
authors.forename: S
authors.initials: S
authors.lastname: Chinnakotla
authors.forename: S
authors.initials: S
authors.lastname: Dawson
authors.forename: H B
authors.initials: HB
authors.lastname: Randall
authors.forename: G
authors.initials: G
authors.lastname: Saracino
authors.forename: G B
authors.initials: GB
authors.lastname: Klintmalm
authors.forename: G B
authors.initials: GB
authors.lastname: Klintmaim
mesh_terms: D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007677:Kidney Function Tests; D008107:Liver Diseases / Q000145:classification / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology / Q000502:physiology*; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus