title: Functional and histological improvement after everolimus rescue of chronic allograft dysfunction in renal transplant recipients.
abstract: BACKGROUND
  We tested the strategy of mTOR inhibitors with calcineurin inhibitor minimization in renal transplant recipients with known chronic allograft dysfunction.
  
  
  METHODS
  In this open-label, single-arm study, renal transplant patients were recruited after biopsy-confirmed chronic allograft dysfunction in the absence of acute rejection episode within 2 months, with proteinuria <0.8 g/day, and serum creatinine <220 μmol/L or estimated glomerular filtration rate >40 mL/min/1.73 m(2). They were converted to everolimus (aiming for trough everolimus level 3-8 ng/mL) with cyclosporine minimization, to assess the effect on renal function, rate of glomerular filtration rate decline, and longitudinal transplant biopsy at 12 months.
  
  
  RESULTS
  Seventeen Chinese patients (median transplant duration, 4.2 years) were recruited; no patients discontinued study medication. The mean slope of the glomerular filtration rate over time was -4.31±6.65 mL/min/1.73 m(2) per year in the year before everolimus, as compared with 1.29±5.84 mL/min/1.73 m(2) per year in the 12 months of everolimus therapy, a difference of 5.61 mL/min/1.73 m(2) per year (95% confidence interval [CI], 0.40-10.8) favoring everolimus therapy (P=0.036). Serial renal biopsy histology showed significant decrease of tubular atrophy (15.7%±11.3% versus 7.1%±7.3%, P=0.005) and interstitial fibrosis (14.8%±11.5% versus 7.2%±8.2%, P=0.013). Intrarenal expression of TGF-β1 mRNA showed a nonsignificant decrease after everolimus treatment.
  
  
  CONCLUSIONS
  In renal transplant recipients with biopsy-confirmed chronic allograft dysfunction, we found a significant beneficial effect of everolimus rescue therapy and calcineurin inhibitor minimization strategy on the improvement of glomerular filtration rate decline rate. In secondary analysis, everolimus was shown to slow down the disease progression by reducing the tubular atrophy and interstitial fibrosis scoring.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: Kai Ming
authors.initials: KM
authors.lastname: Chow
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: Cheuk Chun
authors.initials: CC
authors.lastname: Szeto
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: Fernand Mac-Moune
authors.initials: FM
authors.lastname: Lai
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: Cathy Choi-Wan
authors.initials: CC
authors.lastname: Luk
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: Bonnie Ching-Ha
authors.initials: BC
authors.lastname: Kwan
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: Chi Bon
authors.initials: CB
authors.lastname: Leung
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: Philip Kam-Tao
authors.initials: PK
authors.lastname: Li
keywords: calcineurin inhibitor; cyclosporine; everolimus; glomerular filtration rate; immunosuppression; mTOR inhibitor; renal transplantation