title: Everolimus as primary immunosuppression in kidney transplantation:  experience in conversion from calcineurin inhibitors.
abstract: BACKGROUND
  We analyzed our clinical experience with everolimus (EVL) and identified prognostic factors for a successful conversion.
  
  
  METHODS
  Retrospective study of 220 kidney recipients consecutively converted to EVL with calcineurin inhibitor elimination. We studied risk factors for proteinuria at 1 year after conversion, decline in renal function, and graft survival.
  
  
  RESULTS
  Baseline creatinine clearance was 52.4±17.8 mL/min vs. 53.4±20.1 mL/min 1 year after conversion (P=0.150). Median proteinuria increased from 304 mg/day (interquartile range 160-507) to 458 mg/day (interquartile range 238-892; P<0.001). Risk factors for development of proteinuria ≥900 mg/day (P75) at 1-year postconversion were creatinine clearance less than 60 mL/min (odds ratio [OR] 3.37; 95% confidence interval [CI]: 1.15-9.89), serum triglycerides ≥150 mg/day (OR 4.35; 95% CI: 1.70-11.17), no treatment with prednisone (OR 3.04; 95% CI: 1.22-7.59), baseline proteinuria ≥550 mg/day (OR 10.37; 95% CI: 3.99-26.99), and conversion ≥3 years after transplant (OR 5.77; 95% CI: 1.89-17.59). An interaction was observed between baseline proteinuria and time to conversion: in patients with baseline proteinuria ≥550 mg/day, the risk of developing proteinuria ≥900 mg/day was 77.1% if they were converted after ≥3 years posttransplant. However, this risk was 29.8% in the subgroup converted before (P=0.02). Actuarial graft survival at 1 and 4 years postconversion was 98.2% and 86.5%, respectively. Baseline proteinuria ≥550 mg/day was a risk factor for graft loss in patients converted after the third year but not in patients converted before this time. EVL discontinuation rate was 24% in the first year postconversion.
  
  
  CONCLUSIONS
  Conversion to EVL and elimination of calcineurin inhibitors is safe. Success depends on not making late conversions and not converting patients with high baseline proteinuria.
authors.affiliation: Nephrology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain. sanchezfruct@telefonica.net
authors.forename: Ana I
authors.initials: AI
authors.lastname: Sánchez-Fructuoso
authors.forename: Juan C
authors.initials: JC
authors.lastname: Ruiz
authors.forename: Natividad
authors.initials: N
authors.lastname: Calvo
authors.forename: Emilio
authors.initials: E
authors.lastname: Rodrigo
authors.forename: Isabel
authors.initials: I
authors.lastname: Perez-Flores
authors.forename: Carlos
authors.initials: C
authors.lastname: Gómez-Alamillo
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández-Pérez
authors.forename: Manuel
authors.initials: M
authors.lastname: Arias
authors.forename: Alberto
authors.initials: A
authors.lastname: Barrientos
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D015331:Cohort Studies; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000453:epidemiology; D051437:Renal Insufficiency / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus