Positive effects of single-daily high-dose mizoribine therapy after cyclophosphamide in young children with steroid-dependent nephrotic syndrome
- 80 Downloads
Mizoribine (MZR) therapy after cyclophosphamide (CPM) therapy may be an attractive option in patients with steroid-dependent nephrotic syndrome (SDNS) for the purpose of maintaining remission. This is because CPM is administered only once due to its severe side effects such as gonadal toxicity. However, the long-term prognosis after the treatment regimen remains unknown.
We retrospectively analyzed the clinical course (median follow-up, 5.9 years) of 54 young children with SDNS (43 boys; age < 10 years) who had undergone 12-week CPM therapy. The patients were classified into two groups: group A, undergoing MZR therapy for > 12 months for maintaining remission after CPM therapy (N = 36), and group B, undergoing CPM monotherapy (N = 18).
For 2 years after CPM therapy, 21 of the 36 group A patients were in sustained remission, whereas only 4 of the 18 group B patients had maintained remission (58% vs. 22%, p < 0.05). Furthermore, the rate of regression to SDNS after CPM was significantly lower in group A than in group B (6% vs. 39%, p < 0.05). At the last follow-up (mean age, 10.9 years), 27 of the 36 group A patients (75%) had not received any steroid-sparing agent after the treatment regimen.
Single daily high-dose MZR therapy after CPM therapy may have positive outcomes in young children with SDNS in the long term.
KeywordsMizoribine Cyclophosphamide Steroid-dependent nephrotic syndrome Young children
SF received clinical research funding B at Saitama Children’s Medical Center.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Research Committee and/or National Research Committee at which the study was conducted (approval number 2018-02-19) with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all participants included in this study.
- 2.Ishikura K, Matsumoto S, Sako M, Tsuruga K, Nakanishi K, Kamei K, Saito H, Fujinaga S, Hamasaki Y, Chikamoto H, Ohtsuka Y, Komatsu Y, Ohta T, Nagai T, Kaito H, Kondo S, Ikezumi Y, Tanaka S, Kaku Y, Iijima K, Japanese Society for Pediatric Nephrology, Japanese Society for Pediatric Nephrology. Clinical practice guideline for pediatric idiopathic nephrotic syndrome 2013: medical therapy. Clin Exp Nephrol. 2015;19:6–33.CrossRefGoogle Scholar
- 7.Ishikura K, Yoshikawa N, Hattori S, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Yata N, Ando T, Honda M, for Japanese Study Group of Renal Disease in Children. Treatment with microemulsified cyclosporine in children with frequently relapsing nephrotic syndrome. Nephrol Dial Transpl. 2010;25:3956–62.CrossRefGoogle Scholar
- 8.Iijima K, Sako M, Oba MS, Ito S, Hataya H, Tanaka R, Ohwada Y, Kamei K, Ishikura K, Yata N, Nozu K, Honda M, Nakamura H, Nagata M, Ohashi Y, Nakanishi K, Yoshikawa N, Japanese Study Group of Kidney Disease in Children. Cyclosporine C2 monitoring for the treatment of frequently relapsing nephrotic syndrome in children: a multicenter randomized phase II trial. Clin J Am Soc Nephrol. 2014;9:271–8.CrossRefGoogle Scholar
- 9.Ishikura K, Yoshikawa N, Nakazato H, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Ito S, Yata N, Ando T, Honda M, Japanese Study Group of Renal Disease in Children. Two-year follow-up of a prospective clinical trial of cyclosporine for frequently relapsing nephrotic syndrome in children. Clin J Am Soc Nephrol. 2012;7:1576–83.CrossRefGoogle Scholar
- 10.Ishikura K, Yoshikawa N, Nakazato H, Sasaki S, Nakanishi K, Matsuyama T, Ito S, Hamasaki Y, Yata N, Ando T, Iijima K, Honda M, Japanese Study Group of Renal Disease in Children. Morbidity in children with frequently relapsing nephrosis: 10-year follow-up of a randomized controlled trial. Pediatr Nephrol. 2015;30:459–68.CrossRefGoogle Scholar
- 16.Cammas B, Harambat J, Bertholet-Thomas A, Bouissou F, Morin D, Guigonis V, Bendeddouche S, Afroukh-Hacini N, Cochat P, Llanas B, Decramer S, Ranchin B. Long-term effects of cyclophosphamide therapy in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. Nephrol Dial Transpl. 2011;26:178–84.CrossRefGoogle Scholar
- 17.Vester U, Kranz B, Zimmermann S, Hoyer PF. Cyclophosphamide in steroid-sensitive nephrotic syndrome: outcome and outlook. Pediatr Nephrol. 2003;18:661–4.Google Scholar
- 23.Nakajo A, Khoshnoodi J, Takenaka H, Hagiwara E, Watanabe T, Kawakami H, Kurayama R, Sekine Y, Bessho F, Takahashi S, Swiatecka-Urban A, Tryggvason K, Yan K. Mizoribine corrects defective nephrin biogenesis by restoring intracellular energy balance. J Am Soc Nephrol. 2007;18:2554–64.CrossRefGoogle Scholar