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Assessment of factors associated with mizoribine responsiveness in children with steroid-dependent nephrotic syndrome

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Abstract

Background

Several immunosuppressants have been used to treat children with steroid-dependent nephrotic syndrome (SDNS). Mizoribine (MZR) is an immunosuppressant used to maintain remission in children with SDNS, although its effectiveness for treating SDNS remains controversial. Therefore, in this study, we assessed the clinical factors associated with children having SDNS who were successfully treated with MZR.

Methods

A total of 47 children with SDNS who underwent MZR treatment were retrospectively evaluated. Clinical features including pharmacokinetics after MZR administration were compared between MZR responders and non-responders.

Results

The comparison of the two groups revealed no significant differences in age, body weight (BW), daily dose of MZR per BW, serum concentration 2 h after administration (C2), peak serum concentration (Cmax), and area under the concentration curve 0–4 h after administration (AUC0–4). C2/(single dose/BW), Cmax/(single dose/BW), and AUC0–4/(single dose/BW) were significantly higher in the MZR responders than in the non-responders (all p < 0.01). Receiver operating characteristic analysis revealed that the cutoff values of C2 (single dose/kg), Cmax/(single dose/BW), and AUC0–4/(single dose/BW) were 0.55, 0.58, and 1.37, respectively.

Conclusions

MZR is a useful immunosuppressant for treating frequent-relapse NS in children who are susceptible to the drug. The efficacy of MZR may be associated with not only serum concentrations defined by the dosage or absorption efficiency through MZR transporters, but also the susceptibility defined by the expression level and performance of MZR transporters on the target cells.

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Authors and Affiliations

  1. Department of Pediatrics, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan

    Tomomi Kondoh, Yohei Ikezumi, Katsuyuki Yokoi, Yoko Nakajima, Yuji Matsumoto, Naonori Kumagai, Tetsuya Ito & Tetsushi Yoshikawa

  2. Department of Pediatrics, Niigata University Medical and Dental Hospital, Niigata, Japan

    Masahiro Kaneko, Hiroya Hasegawa & Takeshi Yamada

Authors
  1. Tomomi Kondoh
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  2. Yohei Ikezumi
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  3. Katsuyuki Yokoi
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  4. Yoko Nakajima
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  5. Yuji Matsumoto
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  6. Masahiro Kaneko
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  7. Hiroya Hasegawa
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  8. Takeshi Yamada
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  9. Naonori Kumagai
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  10. Tetsuya Ito
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  11. Tetsushi Yoshikawa
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Corresponding author

Correspondence to Yohei Ikezumi.

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The authors have declared that no conflict of interest exists.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number HM18-119) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any animal studies performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Kondoh, T., Ikezumi, Y., Yokoi, K. et al. Assessment of factors associated with mizoribine responsiveness in children with steroid-dependent nephrotic syndrome. Clin Exp Nephrol 23, 1154–1160 (2019). https://doi.org/10.1007/s10157-019-01754-1

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  • DOI: https://doi.org/10.1007/s10157-019-01754-1

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