title: Efficacy and Safety of Tacrolimus Versus Cyclophosphamide for Primary Membranous Nephropathy: A Meta-Analysis.
abstract: OBJECTIVE
  The objective of this systematic review was to compare the efficacy and safety of tacrolimus with cyclophosphamide in primary membranous nephropathy (PMN) patients.
  
  
  METHODS
  We conducted a literature search in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CCRCT). Any study that compared the efficacy or safety between tacrolimus and cyclophosphamide in the adult PMN patients was included.
  
  
  RESULTS
  We included four randomized controlled trials and two prospective cohort studies with 389 PMN patients. The pooled results using the Dersimonian and Laird method showed that renal remission rates at the longest follow-up periods were not significantly different between the tacrolimus and cyclophosphamide groups (overall remission, six trials, n = 389, relative risk [RR] 0.994 [95% confidence interval [CI] 0.768-1.286); complete remission, six trials, n = 389, RR 1.256 [95% CI 0.733-2.150]). Further analyses found that tacrolimus was comparable with cyclophosphamide for inducing renal remission within 1 year but inferior to cyclophosphamide after 1-year follow-up. It should be noted that only two studies reported the outcomes after 1-year follow-up, which might be considered as weak evidence. The rates of relapse and the drop-outs due to adverse effects were not significantly different (relapse, six trials, n = 389, RR 2.244 [95% CI 0.892-5.644]; drop-outs, six trials, n = 389, RR 1.330 [95% CI 0.412-4.291]). However, the cyclophosphamide group had a significantly higher risk of leukopenia than the tacrolimus group (four trials, n = 216, RR 0.203 [95% CI 0.045-0.916]), whereas the rates of tremor were significantly higher in the tacrolimus group than in the cyclophosphamide group (three trials, n = 202, RR 8.939 [95% CI 1.694-47.173]).
  
  
  CONCLUSIONS
  The quality and short follow-up durations of the studies limited the reliability of our conclusions.
  
  
  CONCLUSIONS
  Tacrolimus was comparable with cyclophosphamide for inducing renal remission of PMN patients within 1 year, but the long-term effects need to be investigated. The cyclophosphamide group had a significantly higher risk of leukopenia, whereas the tacrolimus group had significantly higher rates of tremor. These conclusions need to be further verified.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
authors.forename: Lin-Bo
authors.initials: LB
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China. catherine-ll@126.com.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Liu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
authors.forename: Li-Ning
authors.initials: LN
authors.lastname: Wang
mesh_terms: D003520:Cyclophosphamide / Q000009:adverse effects* / Q000627:therapeutic use*; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D016559:Tacrolimus