title: Calcineurin inhibitor sparing with mycophenolate in kidney transplantation: a systematic review and meta-analysis.
abstract: BACKGROUND
  Limiting the exposure of kidney transplant recipients to calcineurin inhibitors (CNIs) has potential merit, but there is no clear consensus on the utility of current strategies. In an attempt to aid clarification, we conducted a systematic review and meta-analysis of randomized trials that assessed CNI sparing (minimization or elimination) with mycophenolate as sole adjunctive immunosuppression.
  
  
  METHODS
  The search strategy identified trials where CNI sparing was accompanied by the continuation of, or conversion to, mycophenolate and compared with standard or higher dose CNI therapy. Two investigators independently examined each trial for eligibility, quality, and outcome measures. Additional subgroup analyses were assessed: (1) de novo CNI sparing; (2) elective CNI sparing beyond 2 months posttransplantation; and (3) CNI sparing for transplant dysfunction.
  
  
  RESULTS
  Nineteen randomized controlled trials met the inclusion criteria permitting analysis of 3312 renal transplant recipients with median follow-up of 12 months. CNI sparing significantly improved glomerular filtration rate (weighted mean difference 4.4 mL/min, 95% confidence interval [CI] 2.9-5.9, P<0.001); with some evidence, albeit weak, of improved graft survival (odds ratio 0.72, 95% CI 0.52-1.01, P=0.06). Acute rejection rates were only increased after elective CNI elimination (odds ratio 2.23, 95% CI 1.57-3.17, P<0.001). There were no significant differences in mortality, malignancy or incidence of infections.
  
  
  CONCLUSIONS
  CNI sparing strategies with adjunctive mycophenolate may play an important role in kidney transplant recipients. Improvements in short-term graft function, and possibly graft survival, are achievable. Longer term studies are needed to substantiate the short-term benefits, and refining elective CNI elimination protocols may help to reduce the risk of rejection.
authors.affiliation: Department of Nephrology and Kidney Transplantation, Renal Institute of Birmingham, University Hospital Birmingham, Edgbaston, Birmingham, United Kingdom. j.moore.3@bham.ac.uk
authors.forename: Jason
authors.initials: J
authors.lastname: Moore
authors.forename: Lee
authors.initials: L
authors.lastname: Middleton
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
authors.forename: Dwomoa
authors.initials: D
authors.lastname: Adu
authors.forename: Simon
authors.initials: S
authors.lastname: Ball
authors.forename: Mark A
authors.initials: MA
authors.lastname: Little
authors.forename: Andrew
authors.initials: A
authors.lastname: Ready
authors.forename: Keith
authors.initials: K
authors.lastname: Wheatley
authors.forename: Richard
authors.initials: R
authors.lastname: Borrows
mesh_terms: D065095:Calcineurin Inhibitors; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000592:standards / Q000706:statistics & numerical data; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid