Assessment of factors associated with mizoribine responsiveness in children with steroid-dependent nephrotic syndrome
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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.
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.
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.
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.
KeywordsMizoribine Frequent-relapse nephrotic syndrome Steroid-dependent nephrotic syndrome Children
Compliance with ethical standards
Conflict of interest
The authors have declared that no conflict of interest exists.
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.
Informed consent was obtained from all individual participants included in the study.
- 3.Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, et al. Rituximab for Childhood-onset Refractory Nephrotic Syndrome (RCRNS) Study Group. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2014;384(9950):1273–81.CrossRefGoogle Scholar
- 11.Ishikawa H. Mizoribine and mycophenolate mofetil. Curr Med Chem. 1999;6:575–97.Google Scholar
- 13.Sonda K, Takahashi K, Tanabe K, Funchinoue S, Hayasaka Y, Kawaguchi H, et al. Clinical pharmacokinetic study of mizoribine in renal transplantation patients. Transpl Proc. 1996;28:3643–8.Google Scholar
- 14.Fujieda M, Ishihara M, Morita T, Hayashi A, Okada S, Ohta T, et al. Effect of single-dose oral mizoribine pulse therapy twice per week for frequently relapsing steroid-dependent nephrotic syndrome. Clin Nephrol. 2012;78:40–6.Google Scholar
- 16.Kawasaki Y, Takano K, Isome M, Suzuki J, Suyama K, Kanno H, et al. Efficacy of single dose of oral mizoribine pulse therapy two times per week for frequently relapsing nephrotic syndrome. J Nephrol. 2007;20:52–6.Google Scholar