title: mTOR inhibitor versus mycophenolic acid as the primary immunosuppression regime combined with calcineurin inhibitor for kidney transplant recipients: a meta-analysis.
abstract: BACKGROUND
  A number of studies have provided information regarding the risks and benefits of mammalian target of rapamycin inhibitors (mTOR-I) combined with calcineurin inhibitors (CNI) versus mycophenolic acid (MPA).
  
  
  METHODS
  Medline, Embase and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials comparing mTOR-I to MPA as the primary immunosuppressive regimen in combination with CNI were selected and meta-analyzed.
  
  
  RESULTS
  Eleven randomized controlled trials consisting of 4930 patients in total were included. No significant difference was observed in the risk of biopsy-proven acute rejection and patient death between the two groups. However, an increased risk of graft loss (relative risk (RR) = 1.20) and inferior graft function (creatinine clearance, weighted mean difference (WMD) = -2.41 μmol/L) were demonstrated in mTOR-I-treated patients. Patients treated with mTOR-I had a higher risk of new-onset diabetes mellitus (RR = 1.32), dyslipidemia, proteinuria (RR = 1.79), peripheral edema (RR = 1.34), thrombocytopenia (RR = 1.97) and lymphocoele (RR = 1.80), but a lower risk of cytomegalovirus infection (RR = 0.40), malignancy (RR = 0.64) and leucopenia (RR = 0.43). There was no difference in diarrhea, anemia, urinary tract infection, polyoma virus infection and impaired wound healing when mTOR-I was compared with MPA.
  
  
  CONCLUSIONS
  mTOR-I showed no particular superiority to MPA. Notably, mTOR-I had an increased risk of graft loss when combined with CNI, even when combined with a reduced dose of CNI. Therefore, the optimal dosage strategies for mTOR-I and CNI need to be further explored.
authors.affiliation: Kidney Disease Center, The First Affiliated Hospital, Medical School of Zhejiang University, Qingchun Rd, Hangzhou, Zhejiang, China. xiexishao@126.com.
authors.forename: Xishao
authors.initials: X
authors.lastname: Xie
authors.affiliation: Kidney Disease Center, The First Affiliated Hospital, Medical School of Zhejiang University, Qingchun Rd, Hangzhou, Zhejiang, China. amandakimi@zju.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Kidney Disease Center, The First Affiliated Hospital, Medical School of Zhejiang University, Qingchun Rd, Hangzhou, Zhejiang, China. lxx1989lxx@163.com.
authors.forename: Xiuxiu
authors.initials: X
authors.lastname: Lai
authors.affiliation: Kidney Disease Center, The First Affiliated Hospital, Medical School of Zhejiang University, Qingchun Rd, Hangzhou, Zhejiang, China. xiaoxiangno2@sina.com.
authors.forename: Shilong
authors.initials: S
authors.lastname: Xiang
authors.affiliation: Kidney Disease Center, The First Affiliated Hospital, Medical School of Zhejiang University, Qingchun Rd, Hangzhou, Zhejiang, China. zfshou@zju.edu.cn.
authors.forename: Zhangfei
authors.initials: Z
authors.lastname: Shou
authors.affiliation: Kidney Disease Center, The First Affiliated Hospital, Medical School of Zhejiang University, Qingchun Rd, Hangzhou, Zhejiang, China. chenjhzju@sina.com.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Chen
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020123:Sirolimus / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus