Positive effects of single-daily high-dose mizoribine therapy after cyclophosphamide in young children with steroid-dependent nephrotic syndrome

Mizutani, Akira; Fujinaga, Shuichiro; Sakuraya, Koji; Hirano, Daishi; Shimizu, Toshiaki

doi:10.1007/s10157-018-1628-5

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…We previously demonstrated that high-dose mizoribine after cyclophosphamide therapy might be associated with favorable outcomes in pediatric patients with moderatedose (< 0.6 mg/kg/day) steroid dependence (Mizutani et al 2019). In the present study, most patients in the nonresponse group were able to discontinue SDNS after switching from mizoribine to cyclophosphamide.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Treatment Response and Long-Term Outcomes in Young Children with Steroid-Dependent Nephrotic Syndrome Treated with High-Dose Mizoribine as First-Line Steroid-Sparing Agent

Fujinaga

Endo

Morishita

et al. 2022

Tohoku J. Exp. Med.

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Mizoribine may be a safe and effective treatment for children with steroid-dependent nephrotic syndrome (SDNS). However, predictors of treatment response and long-term outcomes after mizoribine discontinuation remain unknown. We retrospectively reviewed the clinical course of 22 children aged ≤ 10 years (median age, 5.3 years) with SDNS who received high-dose mizoribine as the initial steroid-sparing agent (SSA). Mizoribine was administered at a single daily dose of 10 mg/kg (maximum, 300 mg/day) after breakfast. The dose was adjusted to maintain 2-h post-dose mizoribine levels of > 3 μg/mL and was tapered off after 12 months of steroid-free remission. Patients who regressed to SDNS were switched from mizoribine to other SSAs. The primary endpoint was probability of survival without regression to SDNS after mizoribine initiation. Ten patients were able to discontinue SDNS (response group), whereas twelve were switched from mizoribine to other SSAs (non-response group) during a median observation period of 6.0 years after mizoribine. The steroid-dependent dose prior to mizoribine was significantly lower in the response group than in the non-response group (p < 0.05). The Kaplan-Meier analysis revealed that the probability of regression-free survival was significant higher in patients with steroid-dependent dose of < 0.25 mg/kg/day than in those with steroid-dependent dose of ≥ 0.25 mg/kg/day (p < 0.05). During a median follow-up of 5.5 years after mizoribine discontinuation, all but one patient did not develop SDNS. High-dose mizoribine may be an attractive treatment option as initial SSA in young children with low steroid-dependent dose for improved long-term outcomes.

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Section: Discussionmentioning

confidence: 99%

Predictors of Treatment Response and Long-Term Outcomes in Young Children with Steroid-Dependent Nephrotic Syndrome Treated with High-Dose Mizoribine as First-Line Steroid-Sparing Agent

Fujinaga

Endo

Morishita

et al. 2022

Tohoku J. Exp. Med.

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“…After excluding 5,587 duplicates and 7,527 studies based on their titles and abstracts, 479 studies remained for full-text evaluation. Eventually, 15 studies (9)(10)(11)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) were included in this systematic review and network meta-analysis. The study selection process is depicted in Figure 1.…”

Section: Study Selectionmentioning

confidence: 99%

“…The 15 eligible studies (9)(10)(11)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) included 1053 pediatric patients with FRSDNS. The year of publication covered 2008 to 2022, and 9 countries were involved.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Immunosuppressive agents for frequently relapsing/steroid-dependent nephrotic syndrome in children: a systematic review and network meta-analysis

Zhu,

Chen,

Zhang

et al. 2024

Front. Immunol.

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AimThis study aimed to systematically compare the efficacy of various immunosuppressive agents in treating pediatric frequently relapsing or steroid-dependent nephrotic syndrome (FRSDNS).MethodsWe conducted systematic searches of PubMed, Embase, the Cochrane Library, and the Web of Science up to May 23, 2023. Outcome measures included relapses within 1 year, mean cumulative exposure to corticosteroids, patients with treatment failure at 1 year, relapse-free survival during 1 year, and adverse events. The quality of the included studies was evaluated using the modified Jadad scale, the Methodological Index for Non-Randomized Studies (MINORS), and the modified Newcastle-Ottawa Scale (NOS).ResultsRituximab was found to be the most likely (92.44%) to be associated with the fewest relapses within 1 year and was also most likely (99.99%) to result in the lowest mean cumulative exposure to corticosteroids. Rituximab had the highest likelihood (45.98%) of being associated with the smallest number of patients experiencing treatment failure at 1 year. CsA was most likely (57.93%) to achieve the highest relapse-free survival during 1 year, followed by tacrolimus (26.47%) and rituximab (30.48%). Rituximab showed no association with serious side effects and had comparable adverse effects to ofatumumab and tacrolimus.ConclusionRituximab may be the most favorable immunosuppressive agent for treating pediatric FRSDNS. Nephrologists should consider this drug, along with their clinical experience, patient characteristics, and cost considerations, when choosing a treatment approach.

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“…Since 2007, a single dose (375 mg/m 2 ; maximum, 500 mg) of rituximab (RTX; Rituxan, injection, Zenyaku Co., Tokyo, Japan) has been administered for patients with complicated SDNS after CsA or MMF treatment [14]. For young children with SDNS aged < 10 years and before puberty, cyclophosphamide (Endoxan, oral formulation, Shionogi Co., Osaka, Japan) was administered at a single daily dose of 2-2.5 mg/kg/day for 12 weeks (cumulative dosage, 200 mg/kg) [15]. For young children with low-dose steroid dependency, a single, daily, high dose of mizoribine (10 mg/kg/day maximum, 300 mg/day; Bredinine, oral formulation, Asahikasei, Tokyo, Japan) was offered as a treatment option [16].…”

Section: Treatment Protocolmentioning

confidence: 99%

Adult survivors of childhood-onset steroid-dependent and steroid-resistant nephrotic syndrome treated with cyclosporine: a long-term single-center experience

Takemasa,

Fujinaga,

Nakagawa

et al. 2023

Pediatr Nephrol

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BackgroundAlthough evidence has con rmed that cyclosporine A (CsA) is e cacious against childhood-onset steroid-dependent and steroid-resistant nephrotic syndrome (SD/SRNS), some patients may continue to relapse during adulthood. However, predictive factors for active disease into adulthood and renal complications in this cohort remain unknown. MethodsWe conducted a retrospective study on the long-term outcomes of 81 young adults with childhood-onset SD/SRNS treated with CsA. The primary endpoint was the probability of active disease into adulthood, de ned as disease relapse or ongoing immunosuppressive treatment throughout the 2 years preceding the last follow-up. ResultsAt last follow-up (median age, 23.2 years; median disease duration, 15.8 years), 44 adult patients (54%) continued to have active disease, whereas 16 (20%) and 16 (20%) patients developed mild chronic kidney disease (CKD) and hypertension, respectively. Young age at NS onset and history of relapse during initial CsA treatment were independent predictive factors for active disease into adulthood. Acute kidney injury at NS onset, focal segmental glomerulosclerosis, and irreversible CsA nephrotoxicity were identi ed as risk factors for the development of CKD, whereas older age was identi ed as a risk factor for the development of renal complications. No correlation was observed between active disease into adulthood and the development of renal complications. ConclusionsAfter CsA initiation for SD/SRNS, more than half of adult survivors continued to have active disease.Long-term follow-up is necessary to identify the development of renal complications later in adulthood that can be attributed to prior disease and CsA treatment in childhood, irrespective of disease activity.

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Positive effects of single-daily high-dose mizoribine therapy after cyclophosphamide in young children with steroid-dependent nephrotic syndrome

Abstract: Single daily high-dose MZR therapy after CPM therapy may have positive outcomes in young children with SDNS in the long term.

Cited by 7 publications

References 29 publications

Predictors of Treatment Response and Long-Term Outcomes in Young Children with Steroid-Dependent Nephrotic Syndrome Treated with High-Dose Mizoribine as First-Line Steroid-Sparing Agent

Predictors of Treatment Response and Long-Term Outcomes in Young Children with Steroid-Dependent Nephrotic Syndrome Treated with High-Dose Mizoribine as First-Line Steroid-Sparing Agent

Immunosuppressive agents for frequently relapsing/steroid-dependent nephrotic syndrome in children: a systematic review and network meta-analysis

Adult survivors of childhood-onset steroid-dependent and steroid-resistant nephrotic syndrome treated with cyclosporine: a long-term single-center experience

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