title: Controlled-dose versus fixed-dose mycophenolate mofetil for kidney transplant recipients: a systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Although mycophenolate mofetil (MMF) is recommended at a fixed dose, there is increasing interest in controlled-dose (CD) MMF based on therapeutic drug monitoring. We systematically evaluated published randomized controlled trials (RCTs) on the efficacy and safety of CD versus fixed-dose MMF for kidney transplant recipients.
  
  
  METHODS
  The electronic databases Medline, Embase, and Cochrane Library (up to June 2012) were searched to identify relevant RCTs. Two reviewers independently applied the study selection criteria, examined the study quality, and extracted the data. Dichotomous measures were expressed as relative risk (RR) and continuous outcomes were expressed as weighted mean difference, both with 95% confidence intervals (CIs). All statistical analyses were performed using Review Manager 5.1.6.
  
  
  RESULTS
  Four RCTs met our selection criteria and included 1755 de novo recipients. The differences between CD and fixed-dose MMF in treatment failure (RR, 0.95; 95% CI, 0.82-1.10; P=0.52), serum creatinine clearance (weighted mean difference, 2.46; 95% CI, -1.15 to 6.07; P=0.18), total gastrointestinal adverse events (RR, 1.23; 95% CI, 0.65-2.35; P=0.53), diarrhea (RR, 1.08; 95% CI, 0.92-1.25; P=0.35), anemia (RR, 1.24; 95% CI, 0.95-1.64; P=0.12), leukopenia (RR, 1.12; 95% CI, 0.93-1.35; P=0.25), thrombocytopenia (RR, 0.80; 95% CI, 0.47-1.36; P=0.41), and malignancy (RR, 0.61; 95% CI, 0.27-1.38; P=0.23) were not statistically significant. Furthermore, total infections were more frequent in the CD group (36.0% vs. 30.9%; RR, 1.16; 95% CI, 1.03-1.30; P=0.01).
  
  
  CONCLUSIONS
  Based on current evidence, CD MMF administration cannot be recommended as routine practice for kidney transplant recipients. Therapeutic drug monitoring for MMF may be targeted toward high-risk recipients, who should be identified in future studies.
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xianding
authors.initials: X
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Qin
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Huang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Quantao
authors.initials: Q
authors.lastname: Zeng
authors.forename: Hao
authors.initials: H
authors.lastname: Zeng
authors.forename: Yiping
authors.initials: Y
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
mesh_terms: D016903:Drug Monitoring; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods* / Q000502:physiology; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid