title: Late conversion from calcineurin inhibitor-based to sirolimus-based immunosuppression due to chronic toxicity: a prospective study with protocol biopsy amendment.
abstract: BACKGROUND
  There is an emerging consensus on conversion from calcineurin inhibitor (CNI)-based regimens to proliferation signal inhibitor (PSI)-based protocols for the prevention of a progressive decline in graft function due to CNI toxicity.
  
  
  METHODS
  Thirty-one primary renal transplant recipients within 17-48 years of age (mean, 32.2 +/- 1.6) were enrolled in this dual-center study. Eligible patients had a baseline (pre-engraftment) biopsy and completed at least 12 months of follow-up with deteriorating graft function indicative of chronic CNI toxicity with or without nonspecific interstitial fibrosis/tubular atrophy (IF/TA) on a biopsy specimen. A fast conversion protocol, being defined as a 50% initial reduction followed by complete withdrawal of CNI drug within 2 weeks of introducing rapamycin was performed in all patients. A sirolimus (SRL) loading dose was not prescribed; all subjects directly received maintenance (2-5 mg/d) doses of the drug. The primary endpoint of this study was assessement of renal function using cGFR and renal histology by protocol biopsy at 1 year after conversion.
  
  
  RESULTS
  The mean follow-up after conversion was 21.6 months. The difference between cGFR before compared with cGFR after 12 months after conversion (40.8 +/- 2.36 mL/min vs 55.7 +/- 3.6 mL/min; P < .000) and at the last follow-up (40.8 +/- 2.36 mL/min vs 53.8 +/- 2.96 mL/min; P < .000) was significant. The mean IF/TA with glomerulosclerosis and chronic vasculopathy scores of biopsy specimens at baseline, during conversion, and at 12 months of the study were 2.25 +/- 0.3, 3.30 +/- 0.24, and 3.0 +/- 0.30, respectively. The change in scores was indicative of mild progression; however, the difference was not significant. IF/TA, glomerulosclerosis, and chronic vasculopathy scores improved in 8 (30%) subjects, remained unchanged in 11 (42%) and worsened in 7 (28%) after 1 year of SRL therapy. After conversion there was no patient or graft loss in this group. Moreover, SCr and GFR improved in 21 or 29 patients (72%), remained stable in 4 (14%), and decreased in 4 (14%) patients. The predictors of successful conversion in our study were GFR > or = 40.6 mL/min, SCr < or = 2.34 mg/dL, and histological allograft damage score < or =3.
  
  
  CONCLUSIONS
  SRL-MPA/MMF-ST combination may be a good therapeutic strategy against chronic CNI toxicity, particularly for patients whose conversion biopsy specimens demonstrated mild IF/TA, glomerulosclerosis, and chronic vasculopathy scores (< or =3.1 +/- 0.3).
authors.affiliation: T.C.S.B. Izmir Egitim ve Arastirma Hastanesi Organ Nakli Merkezi, Izmir/Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Uslu
authors.forename: H
authors.initials: H
authors.lastname: Töz
authors.forename: S
authors.initials: S
authors.lastname: Sen
authors.forename: F T
authors.initials: FT
authors.lastname: Alkan
authors.forename: A
authors.initials: A
authors.lastname: Nart
authors.forename: A
authors.initials: A
authors.lastname: Aykas
authors.forename: M
authors.initials: M
authors.lastname: Doğan
authors.forename: H
authors.initials: H
authors.lastname: Postaci
authors.forename: T
authors.initials: T
authors.lastname: Sahin
authors.forename: C
authors.initials: C
authors.lastname: Simşek