title: Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data.
abstract: OBJECTIVE
  To compare the positive and negative effects of tacrolimus and ciclosporin as initial treatment for renal transplant recipients.
  
  
  METHODS
  Systematic review.
  
  
  METHODS
  Reports of comparative randomised trials of tacrolimus and ciclosporin identified by searches of Medline, Embase, the Cochrane Register of Controlled Trials, the Cochrane Renal Group Specialist Register, and conference proceedings.
  
  
  METHODS
  Two reviewers assessed trials for eligibility and quality and extracted data independently. Data were synthesised (random effects model) and results expressed as relative risk (RR), with values < 1 favouring tacrolimus. Subgroup analysis and meta-regression were used to examine potential effect modification by differences in trial design and immunosuppressive co-interventions.
  
  
  RESULTS
  123 reports from 30 trials (4102 patients) were included. At six months, graft loss was significantly reduced in tacrolimus treated recipients (RR = 0.56, 95% confidence interval 0.36 to 0.86), and this effect persisted up to three years. The relative reduction in graft loss with tacrolimus diminished with higher concentrations of tacrolimus (P = 0.04) but did not vary with ciclosporin formulation (P = 0.97) or ciclosporin concentration (P = 0.38). At one year, tacrolimus treated patients had less acute rejection (RR = 0.69, 0.60 to 0.79) and less steroid resistant rejection (RR = 0.49, 0.37 to 0.64) but more diabetes mellitus requiring insulin (RR = 1.86, 1.11 to 3.09), tremor, headache, diarrhoea, dyspepsia, and vomiting. The relative excess of diabetes increased with higher concentrations of tacrolimus (P = 0.003). Ciclosporin treated recipients had significantly more constipation and cosmetic side effects. No differences were seen in infection or malignancy.
  
  
  CONCLUSIONS
  Treating 100 recipients with tacrolimus instead of ciclosporin for the first year after transplantation avoids 12 patients having acute rejection and two losing their graft but causes an extra five patients to develop insulin dependent diabetes. Optimal drug choice may vary between patients.
authors.affiliation: Cochrane Renal Group, Centre for Kidney Research, Children's Hospital at Westmead, Westmead, NSW 2145, Australia. angelaw2@chw.edu.au
authors.forename: Angela C
authors.initials: AC
authors.lastname: Webster
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Woodroffe
authors.forename: Rod S
authors.initials: RS
authors.lastname: Taylor
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Chapman
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
mesh_terms: D016572:Cyclosporine / Q000627:therapeutic use*; D005544:Forecasting; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus