title: A retrospective 12-month study of conversion to everolimus in lung transplant recipients.
abstract: BACKGROUND
  Everolimus has potent antifibrotic effects that may potentially affect the clinical course of bronchiolitis obliterans syndrome (BOS) or provide nephroprotective immunosuppressive regimens for lung transplantation.
  
  
  METHODS
  We retrospectively assessed the 12-month outcomes of the conversion to everolimus among lung recipients in six Spanish centers.
  
  
  RESULTS
  From March 2005 to December 2007, 65 lung recipients who were at a mean posttransplantation time of 10.2 ± 7.9 months were converted to everolimus, mainly because of BOS (64.6%) or renal insufficiency (RI; 12.3%). The initial dose of everolimus was 1.9 ± 0.6 mg/d and the mean blood trough levels were stable over time (6.4 ± 2.8 ng/mL at 12 months). Conversion to everolimus allowed us to eliminate the calcineurin inhibitor (CNI) in 21% of patients. Among the overall population, the forced expiratory volume at 1 second (FEV(1)) and renal function remained stable. Mean FEV(1) did not change among the 35 (81%) patients surviving BOS at 12 months: preconversion FEV(1): 1.449.5 ± 641.9 mL vs 12-month FEV(1): 1420.0 ± 734.6 mL (P = .866). There was a significant improvement in renal function among the RI patients with mean glomerular filtration rates of 42.2 ± 15.2 mL/min/1.73 m(2) (P = .043) at 6 and 44.4 ± 18.8 mL/min/1.73 m(2) at 12 months, (P = .063) and a decrease in the use of CNIs from 1% of RI patients preconversion to 57% at 6 and 75% at 12 months. With a mean of 8.1- months follow-up (range: 1-31.3) overall survival was 84.6% at 1 year and 50% at 22.3 months. Progressive BOS was the main cause of death. Reasons for everolimus discontinuation were patient death (n = 10), lack of efficacy (n = 4), gastrointestinal adverse events (n = 2), and edema (n = 2).
  
  
  CONCLUSIONS
  BOS and RI were the main indications for conversion to everolimus among lung recipients. Conversion to everolimus improved renal function among patients converted because of RI. The present results were inconclusive regarding effects of everolimus on BOS.
authors.affiliation: Department of Pulmonology, University Hospital Vall d'Hebron, Barcelona, Spain. aroman@vhebron.net
authors.forename: A
authors.initials: A
authors.lastname: Roman
authors.forename: P
authors.initials: P
authors.lastname: Ussetti
authors.forename: F
authors.initials: F
authors.lastname: Zurbano
authors.forename: J M
authors.initials: JM
authors.lastname: Borro
authors.forename: A
authors.initials: A
authors.lastname: Solé
authors.forename: M C
authors.initials: MC
authors.lastname: Carreño
authors.forename: F
authors.initials: F
authors.lastname: Santos
mesh_terms: D000328:Adult; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007677:Kidney Function Tests; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013030:Spain
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus