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

Tomomi Kondoh, Yohei Ikezumi, Katsuyuki Yokoi, Yoko Nakajima, Yuji Matsumoto, Masahiro Kaneko, Hiroya Hasegawa, Takeshi Yamada, Naonori Kumagai, Tetsuya Ito, Tetsushi Yoshikawa

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalClinical and Experimental Nephrology
DOIs
Publication statusPublished - 01-01-2019

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Nephrotic Syndrome
Steroids
Body Weight
Immunosuppressive Agents
bredinin
Serum
ROC Curve
Area Under Curve
Pharmacokinetics
Recurrence

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nephrology
  • Physiology (medical)

Cite this

Kondoh, Tomomi ; Ikezumi, Yohei ; Yokoi, Katsuyuki ; Nakajima, Yoko ; Matsumoto, Yuji ; Kaneko, Masahiro ; Hasegawa, Hiroya ; Yamada, Takeshi ; Kumagai, Naonori ; Ito, Tetsuya ; Yoshikawa, Tetsushi. / Assessment of factors associated with mizoribine responsiveness in children with steroid-dependent nephrotic syndrome. In: Clinical and Experimental Nephrology. 2019.
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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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Assessment of factors associated with mizoribine responsiveness in children with steroid-dependent nephrotic syndrome. / Kondoh, Tomomi; Ikezumi, Yohei; Yokoi, Katsuyuki; Nakajima, Yoko; Matsumoto, Yuji; Kaneko, Masahiro; Hasegawa, Hiroya; Yamada, Takeshi; Kumagai, Naonori; Ito, Tetsuya; Yoshikawa, Tetsushi.

In: Clinical and Experimental Nephrology, 01.01.2019.

Research output: Contribution to journalArticle

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T1 - Assessment of factors associated with mizoribine responsiveness in children with steroid-dependent nephrotic syndrome

AU - Kondoh, Tomomi

AU - Ikezumi, Yohei

AU - Yokoi, Katsuyuki

AU - Nakajima, Yoko

AU - Matsumoto, Yuji

AU - Kaneko, Masahiro

AU - Hasegawa, Hiroya

AU - Yamada, Takeshi

AU - Kumagai, Naonori

AU - Ito, Tetsuya

AU - Yoshikawa, Tetsushi

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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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