title: Superior outcomes in renal transplantation after early cyclosporine withdrawal and sirolimus maintenance therapy, regardless of baseline renal function.
abstract: BACKGROUND
  It has become increasingly important to refine therapeutic strategies according to individual patient characteristics. We evaluated the long-term impact of renal function at the time of withdrawing cyclosporine (CsA) in renal allograft recipients receiving sirolimus (SRL), CsA, and steroids (ST).
  
  
  METHODS
  At 3 months+/-2 weeks, 430 of 525 patients were eligible to be randomized to remain on triple-therapy (SRL-CsA-ST, n=215) or to have CsA withdrawn (SRL-ST, n=215). Patients were divided into quartiles according to their baseline (last value before randomization) calculated GFR: <or=45 ml/min (quartile 1, n=104), >45 to 56 ml/min (quartile 2, n=105), >56 to 67 ml/min (quartile 3, n=112), and >67 ml/min (quartile 4, n=107). All data were included (ITT analysis).
  
  
  RESULTS
  At 4 years, calculated GFR for SRL-CsA-ST vs. SRL-ST was 22.1 vs. 37.7 ml/min (P=0.017), 38.6 vs. 56.6 ml/min (P<0.001), 50.7 vs. 66.8 ml/min (P=0.006), and 62.7 vs. 71.4 ml/min (P=0.436), for quartiles 1 to 4, respectively. Death-censored graft loss ranged from 21.2% vs. 7.7% (SRL-CsA-ST vs. SRL-ST, P=0.092) in quartile 1 to 5.5% vs. 1.9% (P=0.618) in quartile 4. The incidence of death and biopsy-confirmed acute rejection also decreased with increasing baseline GFR, but was not significantly different between treatments. Overall, more patients remained on therapy in the SRL-ST group (46.3% vs. 57.9%, P=0.020).
  
  
  CONCLUSIONS
  Early and complete withdrawal of CsA from a combination of SRL, CsA, and steroids was preferable to continuing on this regimen, regardless of baseline renal function. The benefit was most marked in patients with a baseline calculated GFR<or=45 ml/min.
authors.affiliation: The Queen Elizabeth Hospital, Woodville, South Australia, Australia., and Hospitais da Universidade de Coimbra, Coimbra, Portugal. graeme.russ@nwahs.sa.gov.au
authors.forename: Graeme
authors.initials: G
authors.lastname: Russ
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Segoloni
authors.forename: Rainer
authors.initials: R
authors.lastname: Oberbauer
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mota
authors.forename: Josette
authors.initials: J
authors.lastname: Eris
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
authors.forename: Peter
authors.initials: P
authors.lastname: Friend
authors.forename: Joseph
authors.initials: J
authors.lastname: Lawen
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Schena
authors.forename: Magali
authors.initials: M
authors.lastname: Lelong
authors.forename: James T
authors.initials: JT
authors.lastname: Burke
authors.forename: John F
authors.initials: JF
authors.lastname: Neylan
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D007668:Kidney / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013256:Steroids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D020123:Sirolimus