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Comparison of second-line immunosuppressants for childhood refractory nephrotic syndrome: a systematic review and network meta-analysis
  1. Hai-Dong Fu1,
  2. Gu-Ling Qian2,
  3. Zheng-yang Jiang3
  1. 1Department of Nephrology, The Children's Hospital of Zhejiang University, Hangzhou, China
  2. 2Department of Inherited Metabolic Disease, The Children's Hospital of Zhejiang University, Hangzhou, China
  3. 3Department of Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, New York, USA
  1. Correspondence to Dr Gu-Ling Qian, Department of Inherited Metabolic Disease, The Children's Hospital of Zhejiang University, Bingsheng Road 3333, Hangzhou 3150000, China; qooling{at}


Although, most patients respond initially to therapy for nephrotic syndrome, about 70% of patients have a relapse. Currently, there is no consensus about the most appropriate second-line agent in children who continue to suffer a relapse. This network meta-analysis was designed to compare the efficacy and safety of the commonly used immunosuppressive agents in second-line therapeutic agents (ie, cyclophosphamide, cyclosporine, tacrolimus and mycophenolate mofetil) for refractory childhood nephrotic syndrome. MEDLINE, Cochrane, EMBASE and Google Scholar databases were searched until October 17, 2015 using the following search terms: cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil and childhood nephrotic syndrome. Randomized controlled trials, prospective 2-arm studies and cohort studies were included. 7 studies with 391 patients were included. Bayesian network meta-analysis found that treatment with mycophenolate mofetil had the greatest odds of relapse compared with tacrolimus (pooled OR=49.72, 95% credibility interval (CrI) 1.65 to 2483.32), cyclophosphamide (pooled OR=72.05, 95% CrI 1.44 to 13633.33) and cyclosporine (pooled OR=11.42, 95% CrI 1.03 to 131.60). Rank probability analysis found cyclophosphamide was the best treatment with the lowest relapse rate as compared with other treatments (rank probability=0.58), and tacrolimus was ranked as the second best (rank probability=0.38). Our findings support the use of cyclophosphamide and tacrolimus in treating children with relapsing nephrotic syndrome.

  • Cyclophosphamide

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  • Contributors H-DF contributed to the study concepts and design, and to the editing and reviewing of the manuscript. G-LQ provided definition of intellectual content and was responsible for the literature research and manuscript preparation. Z-yJ participated in the data acquisition and statistical analysis. H-DF is the guarantor.

  • Funding This work is supported by the National Natural Science Foundation of China (81170664).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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