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
- 22 Downloads
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.
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.
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.
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.
KeywordsFrequently relapsing nephrotic syndrome Mizoribine Pharmacokinetic parameters
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.
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.
Compliance with ethical standards
This study was approved by the Institutional Ethics Committee of Nanjing University School of Medicine.
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.KDIGO Clinical Practice Guideline for Glomerulonephritis. Chapter 3: Steroid-sensitive nephrotic syndrome in children. Kidney Int. 2012;2:163–71.Google Scholar
- 3.Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr. Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. J Am Soc Nephrol. 1997;8:769–76.Google Scholar
- 5.Niaudet P, Broyer M, Habib R. Treatment of idiopathic nephrotic syndrome with cyclosporin A in children. Clin Nephrol. 1991;35(Suppl 1):S31–6.Google Scholar
- 13.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
- 26.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