Triple immunosuppressive therapy in steroid‐resistant nephrotic syndrome children with tacrolimus resistance or tacrolimus sensitivity but frequently relapsing

Wu, Boying; Mao, Jianhua; Shen, Huijun; Fu, Haidong; Wang, Jingjing; Liu, Aimin; Gu, Weizhong; Shu, Qiang; Du, Lizhong

doi:10.1111/nep.12351

Cited by 19 publications

(15 citation statements)

References 24 publications

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“…Treatment of SRNS remains a difficult challenge in pediatric nephrology, with patients showing a variable response to immunosuppression, adverse effects of prolonged therapy and risk of progressive renal damage (8). Calcineurin inhibitors including cyclosporine A (CsA) and tacrolimus (TAC) have been recommended by Kidney Disease Improving Global Outcomes (KDIGO) and the Chinese Association of Pediatric Nephrology as initial therapy for children with SRNS (9,10). For less adverse drug effects, mycophenolate mofetil (MMF) in combination with steroids and angiotensin-converting enzyme-inhibitor drugs also shows some efficacy in the management of SRNS and has been used in clinical practice (11,12).…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive Therapy in Children With Steroid-Resistant Nephrotic Syndrome

et al. 2018

Iran J Pediatr

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Background: Treatment of steroid-resistant nephrotic syndrome (SRNS) remains a huge challenge in pediatric patients. Immunosuppressive agents including cyclosporine A (CsA), tacrolimus (TAC) and mycophenolate mofetil (MMF) are recommended for the management of children with SRNS. The aim of this study was to compare the efficacy of CsA, TAC and MMF in children with SRNS and provide guidance for clinical practice. Methods: This is a retrospective analysis of the records of 70 children with SRNS recruited from a children hospital over a period of seven years. They were treated with CsA, TAC and MMF as initial immunosuppressive therapy in addition to steroids. Complete or partial remission was considered a good response. Results: Five (41.7%) of 12 children who were on CsA therapy achieved remission at 6 months and 5 (41.7%) at 12 months. Nine (19.1%) of 47 patients treated with TAC achieved remission at 6 months, 20 (42.6%) at 12 months and 6 (12.8%) within or over 24 months. The remission achieved at 6 months and 12 months was 4 (36.4%) and 2 (18.2%) respectively in MMF group. The relapse rates in children who had achieved remission were 30.0%, 45.7% and 50.0% in CsA, TAC and MMF group respectively. Conclusions: Based on similar baseline characteristics, CsA and TAC as initial therapy for SRNS have a better remission and relapse rates whereas MMF shows a rapid remission effect.

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Section: Introductionmentioning

confidence: 99%

Immunosuppressive Therapy in Children With Steroid-Resistant Nephrotic Syndrome

et al. 2018

Iran J Pediatr

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“…The characteristics of the 18 included trials are summarized in Table 1 [ 4 , 6 – 9 , 17 – 29 ]. Briefly, trial durations ranged from 3 months to 24 months and the enrolled patients ranged in age from 1 year to 18 years old.…”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of immunosuppressive medications for steroid-resistant nephrotic syndrome in children: a systematic review and network meta-analysis

Yang

Guo

et al. 2017

Oncotarget

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BackgroundConventional meta-analyses and randomized controlled trials have shown inconsistent results regarding the efficacy of immunosuppressants for pediatric steroid-resistant nephrotic syndrome (SRNS).ObjectiveTo conduct a network meta-analysis aimed at evaluating the efficacy and safety of available immunosuppressive agents in pediatric patients with SRNS.Study methodsMEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE were searched on January 2017. Data from randomized controlled trials (RCTs) were included. The main outcomes analyzed were efficacy [number/portion with complete remission (CR), number/portion with partial remission (PR), and total number/portion in remission (TR)] and safety [adverse secondary event (ASE) rates].ResultsA meta-analysis of 18 RCTs showed that tacrolimus was more efficacious for achieving CR than intravenous (i.v.) cyclophosphamide, mycophenolate mofetil (MMF), oral cyclophosphamide, leflunomide, chlorambucil, azathioprine, and plaebo/nontreatment (P/NT), and more efficacious than i.v. cyclophosphamide, oral cyclophosphamide, and P/NT in terms of TR outcomes. Cyclosporin was associated with a greater CR rate than i.v. cyclophosphamide, MMF, oral cyclophosphamide, chlorambucil, azathioprine, or P/NT, and associated with a greater TR rate than i.v. cyclophosphamide, oral cyclophosphamide, or P/NT. MMF was found to be more efficacious than i.v. cyclophosphamide and oral cyclophosphamide in terms of TR.ConclusionsTacrolimus and cyclosporine may be preferred initial treatments for children with SRNS. MMF may be another option for this patient population. Further studies of the efficacy and safety of these three drugs in children with SRNS should be pursued.

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“…Still, as discussed in the previous section of this review, MMF as a monotherapy or in dual combination with prednisolone was not superior to CNIs in terms of inducing remission in SRNS [30, 32]. Wu et al then performed a prospective RCT in 18 children with steroid-and TAC-resistant or TAC-dependent nephrotic syndrome [57]. They reported that triple-combination therapy with prednisolone, TAC and one out of MMF, CPM or leflunomide was effective for short-term response and remission at 1 year, with comparable efficacy between the three agents and without significant side effects [57].…”

Section: Therapy For Cni-dependent or Cni-resistant Srnsmentioning

confidence: 99%

“…Wu et al then performed a prospective RCT in 18 children with steroid-and TAC-resistant or TAC-dependent nephrotic syndrome [57]. They reported that triple-combination therapy with prednisolone, TAC and one out of MMF, CPM or leflunomide was effective for short-term response and remission at 1 year, with comparable efficacy between the three agents and without significant side effects [57]. However, prolonged intensive immunosuppression with a combined regimen may predispose patients to serious infectious complications and potential malignancy risk in the long term, and this should be closely monitored.…”

Section: Therapy For Cni-dependent or Cni-resistant Srnsmentioning

confidence: 99%

Current understandings in treating children with steroid-resistant nephrotic syndrome

et al. 2020

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Steroid-resistant nephrotic syndrome (SRNS) remains a challenge for paediatric nephrologists. SRNS is viewed as a heterogeneous disease entity including immune-based and monogenic aetiologies. Because SRNS is rare, treatment strategies are individualized and vary among centres of expertise. Calcineurin inhibitors (CNI) have been effectively used to induce remission in patients with immune-based SRNS; however, there is still no consensus on treating children who become either CNI-dependent or CNI-resistant. Rituximab is a steroid-sparing agent for patients with steroid-sensitive nephrotic syndrome, but its efficacy in SRNS is controversial. Recently, several novel monoclonal antibodies are emerging as treatment option, but their efficacy remains to be seen. Non-immune therapies, such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, have been proven efficacious in children with SRNS and are recommended as adjuvant agents. This review summarizes and discusses our current understandings in treating children with idiopathic SRNS.

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Triple immunosuppressive therapy in steroid‐resistant nephrotic syndrome children with tacrolimus resistance or tacrolimus sensitivity but frequently relapsing

Cited by 19 publications

References 24 publications

Immunosuppressive Therapy in Children With Steroid-Resistant Nephrotic Syndrome

Immunosuppressive Therapy in Children With Steroid-Resistant Nephrotic Syndrome

Efficacy and safety of immunosuppressive medications for steroid-resistant nephrotic syndrome in children: a systematic review and network meta-analysis

Current understandings in treating children with steroid-resistant nephrotic syndrome

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