Immunosuppressive treatment for nephrotic idiopathic membranous nephropathy: a meta-analysis based on Chinese adults

PLoS One. 2012;7(9):e44330. doi: 10.1371/journal.pone.0044330. Epub 2012 Sep 5.

Abstract

Background: Idiopathic membranous nephropathy (IMN) is the most common pathological type for nephrotic syndrome in adults in western countries and China. The benefits and harms of immunosuppressive treatment in IMN remain controversial.

Objectives: To assess the efficacy and safety of different immunosuppressive agents in the treatment of nephrotic syndrome caused by IMN.

Methods: PubMed, EMBASE, Cochrane Library and wanfang, weipu, qinghuatongfang, were searched for relevant studies published before December 2011. Reference lists of nephrology textbooks, review articles were checked. A meta-analysis of randomized controlled trials (RCTs) meeting the criteria was performed using Review Manager.

Main results: 17 studies were included, involving 696 patients. Calcineurin inhibitors had a better effect when compared to alkylating agents, on complete remission (RR 1.61, 95% CI 1.13, to 2.30 P = 0.008), partial or complete remission (effective) (CR/PR, RR 1.29, 95% CI 1.09 to 1.52 P = 0.003), and fewer side effects. Among calcineurin inhibitors, tacrolimus (TAC) was shown statistical significance in inducing more remissions. When compared to cyclophosphamide (CTX), leflunomide (LET) showed no beneficial effect, mycophenolate mofetil (MMF) showed significant beneficial on effectiveness (CR/PR, RR: 1.41, 95% CI 1.16 to 1.72 P = 0.0006) but not significant on complete remission (CR, RR: 1.38, 95% CI 0.89 to 2.13 P = 0.15).

Conclusions: This analysis based on Chinese adults and short duration RCTs suggested calcineurin inhibitors, especially TAC, were more effective in proteinuria reduction in IMN with acceptable side effects. Long duration RCTs were needed to confirm the long-term effects of those agents in nephrotic IMN.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alkylating Agents / pharmacology
  • Calcineurin Inhibitors
  • China
  • Chlorambucil / pharmacology
  • Clinical Trials as Topic
  • Cyclophosphamide / pharmacology
  • Cyclosporine / pharmacology
  • Female
  • Glomerulonephritis, Membranous / drug therapy*
  • Glomerulonephritis, Membranous / immunology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Isoxazoles / pharmacology
  • Leflunomide
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / pharmacology
  • Remission Induction
  • Tacrolimus / pharmacology

Substances

  • Alkylating Agents
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Isoxazoles
  • Chlorambucil
  • Cyclosporine
  • Cyclophosphamide
  • Leflunomide
  • Mycophenolic Acid
  • Tacrolimus

Grants and funding

This work was supported by Shanghai Higher Education Outstanding Young Teacher Scientific Research Special Fund, Shanghai Municipal Education Commission; Outstanding Young Scholars project, Second Military Medical University; Medical Educational Reforming and Research Grant of Changzheng Hospital. This work was funded in part by the National Nature Science Fund of China (81000281). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.