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Usefulness of mizoribine administration in children with frequently relapsing nephrotic syndrome, and the relationship between pharmacokinetic parameters and efficacy: a multicenter prospective cohort study in China

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Abstract

Background

Mizoribine (MZR) is an immunosuppressant used to treat adult nephropathy. There is little experience with the drug in treating Chinese children with frequently relapsing nephrotic syndrome (FRNS). We investigated the efficacy and safety for treating MZR with FRNS. Furthermore, the relationship between efficacy and serum concentration was investigated.

Methods

A prospective multicenter observational 12-month study was performed for evaluating the usefulness of MZR with FRNS. Serum MZR concentration was measured, and the relationships between pharmacokinetic parameters (Cmax, AUC), number of relapses, and urinary protein were evaluated.

Results

Eighty-two pediatric patients from four hospitals were treated with MZR and prednisone. MZR treatment significantly reduced the number of relapses and steroid doses. A correlation between pharmacokinetic parameters and relapses was observed, which fits well with the sigmoidal Emax model. Even in the relationship between pharmacokinetic parameters and urinary proteins, it was recognized that there was a threshold in the pharmacokinetic parameters for the therapeutic effect similar to the results obtained with the sigmoidal Emax model. Eleven patients (13.4%) experienced mild adverse events.

Conclusions

MZR therapy was effective in reducing the number of relapses and steroid doses. No severe adverse reactions were observed. Therapeutically effective serum concentrations were estimated to be Cmax ≥ about 2 μg/mL or AUC ≥ about 10 μg h/mL. MZR and steroid treatment were effective and safe for pediatric FRNS.

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Funding

This study was supported by a grant from the medical innovation team project of Jiangsu Province, China (grant number CXTDA2017022). The authors thank the participants and their parents, and other persons who assisted in undertaking this study. The funders had no role in drafting or submitting this manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China

    Zheng-Kun Xia & Yuan-Fu Gao

  2. Department of Pediatrics, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China

    Li-Ping Rong & Xiao-Yun Jiang

  3. Department of Pediatric Nephrology, Children’s Medical Center, Second Xiangya Hospital, Central South University, Changsha 410011, China

    Xi-Qiang Dang & Zhu-Wen Yi

  4. Department of Nephrology and Rheumatology, Children’s Hospital of Fudan University, Shanghai 201102, China

    Qian Shen & Hong Xu

Authors
  1. Zheng-Kun Xia
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  2. Yuan-Fu Gao
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  3. Li-Ping Rong
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  4. Xi-Qiang Dang
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  5. Qian Shen
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  7. Zhu-Wen Yi
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  8. Hong Xu
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Contributions

YFG, LPR, XQD, and QS contributed to the study design, collection, evaluation, and interpretation of the data. XYJ, ZWY, HX, and ZKX contributed to the study design. All authors contributed to the critical revision and final approval of the manuscript.

Corresponding author

Correspondence to Zheng-Kun Xia.

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Ethical approval

This study was approved by the Institutional Ethics Committee of Nanjing University School of Medicine.

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The authors declare that they have no conflict of interest.

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Xia, ZK., Gao, YF., Rong, LP. et al. Usefulness of mizoribine administration in children with frequently relapsing nephrotic syndrome, and the relationship between pharmacokinetic parameters and efficacy: a multicenter prospective cohort study in China. World J Pediatr 15, 262–269 (2019). https://doi.org/10.1007/s12519-019-00241-7

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  • DOI: https://doi.org/10.1007/s12519-019-00241-7

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