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The effect of calcineurin inhibitors in the induction and maintenance treatment of lupus nephritis: a systematic review and meta-analysis

Abstract

Purpose

To evaluate the efficacy and safety of the calcineurin inhibitors (CNIs) cyclosporine (CyA) and tacrolimus (TAC) in the induction and maintenance treatment of lupus nephritis (LN).

Methods

The Cochrane library, PubMed, Embase, and CENTRAL databases were searched and reviewed up to February 2015. Randomized controlled trials were analyzed using RevMan 5.2 software.

Results

Ten randomized controlled trials were selected and included in this study according to our inclusion and exclusion criteria, and six were included in the meta-analysis. The analysis results indicated that, in induction treatment, no statistically significant difference was observed in the rates of complete remission (CR), partial remission (PR), or response between the CNIs and intravenous cyclophosphamide (ivCYC). However, the rates of adverse events such as infection (RR 0.65, P = 0.04), leukocytopenia (RR 0.32, P = 0.04), and menstruation disorder (RR 0.37, P = 0.01) following the use of the CNIs were remarkably lower than those after ivCYC. No differences in the CR, PR, infection, or leukocytopenia rates were observed between the CNIs and mycophenolate mofetil (MMF). In the maintenance treatment period, the relapse rate between the CNIs and azathioprine (AZA) was similar (RR 0.44, P = 0.27), while the leukocytopenia rate was lower with the CNIs (RR 0.26, P = 0.0005).

Conclusion

The efficacy of the CNIs CyA and TAC in induction therapy for lupus nephritis is comparable to ivCYC and MMF, and they are much safer than ivCYC. CNI treatment during the maintenance period was also as effective as AZA treatment, with a much lower risk of adverse effects. The CNIs CyA and TAC should be recommended for both induction and maintenance therapy of LN.

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Abbreviations

CNIs:

Calcineurin inhibitors

CyA:

Cyclosporine

TAC or FK506:

Tacrolimus

MMF:

Mycophenolate

AZA:

Azathioprine

SLE:

Systemic lupus erythematosus

LN:

Lupus nephritis

ivCYC:

Intravenous cyclophosphamide

CR:

Complete remission

PR:

Partial remission

NFAT:

Nucleus factor of activated T cell

RCTs:

Randomized controlled trials

PICO:

The patient/problem intervention comparison outcome principle

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Authors contribution

Wei Qin. planned the study, analyzed data, and assisted in article preparation. Xiaoyan Zhang and Ling Ji searched the literature, selected articles, extracted data, analyzed data, and composed of the article. Lichuan Yang and Xiaohong Tang assisted in the data analysis. All authors read and approved the final manuscript.

Author information

Correspondence to Wei Qin.

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Conflict of interest

None of the authors have any competing interests.

Additional information

Xiaoyan Zhang and Ling Ji have contributed equally to this article.

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Zhang, X., Ji, L., Yang, L. et al. The effect of calcineurin inhibitors in the induction and maintenance treatment of lupus nephritis: a systematic review and meta-analysis. Int Urol Nephrol 48, 731–743 (2016). https://doi.org/10.1007/s11255-015-1201-z

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Keywords

  • CNIs
  • Lupus nephritis
  • Meta-analysis
  • Systematic review
  • Cyclosporine (CyA)
  • Tacrolimus (TAC)