title: A randomized controlled trial of immunosuppression conversion for the treatment of chronic allograft nephropathy.
abstract: BACKGROUND
  This study was conducted to assess the effect of immunosuppression conversion on progression of chronic allograft nephropathy (CAN).
  
  
  METHODS
  Forty-two cyclosporin-treated renal transplant recipients were studied. Patients were included if they had a negatively sloping reciprocal of creatinine vs time (ROCT) plot for >6 months and biopsy-proven CAN. Patients were excluded if they had previously been treated with tacrolimus/mycophenolate mofetil (MMF) or their serum creatinine was >400 micromol/l. Subjects were randomly treated with either: (A) MMF/reduced dose cyclosporin [MMF for azathioprine 0.5-1.0 g bd; cyclosporin trough level (C(0)): 75-100 ng/ml]; (B) tacrolimus for cyclosporin (C(0): 5-10 ng/ml); or (C) continuation of standard therapy. Glomerular filtration rate (GFR) was measured at baseline and after 6 months.
  
  
  RESULTS
  Two patients started dialysis within 6 months (one each from groups A and B). One patient in group A was intolerant of MMF, six others reported gastrointestinal symptoms and three developed anaemia. Cyclosporin dose was reduced by 24% [interquartile range (IQR): 14-27%] in group A [end-of-study C(0): 99 ng/ml (IQR: 90-113 ng/ml)]. In group B, the end-of-study tacrolimus C(0) was 7 ng/ml (5-9 ng/ml). The end-of-study cyclosporin C(0) in group C was 163 ng/ml (145-215 ng/ml). Comparison of ROCT slopes before and after intervention revealed a treatment advantage for group A (P<0.05). The GFR analysis was supportive (P = 0.05). When patients with GFR <20 ml/min/1.73 m(2) at enrollment were excluded from the analysis, the treatment advantage for group A reached statistical significance (n = 27, P<0.05).
  
  
  CONCLUSIONS
  MMF/reduced dose cyclosporin is superior to tacrolimus-for-cyclosporin and standard dose cyclosporin in patients with CAN, at least in the short term. The cyclosporin dose reduction component is likely to be of particular importance. Other findings suggest that early intervention is beneficial.
authors.affiliation: Department of Renal Medicine, St Jame's University Hospital, Leeds, UK. stovesj@doctors.org.uk
authors.forename: John
authors.initials: J
authors.lastname: Stoves
authors.forename: Charles G
authors.initials: CG
authors.lastname: Newstead
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Baczkowski
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Owens
authors.forename: Marius
authors.initials: M
authors.lastname: Paraoan
authors.forename: Abdul Q
authors.initials: AQ
authors.lastname: Hammad
mesh_terms: D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus