Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children

Larkins, Nicholas; Liu, Isaac D; Willis, Narelle S; Craig, Jonathan C.; Hodson, Elisabeth M

doi:10.1002/14651858.cd002290.pub5

Cited by 69 publications

(86 citation statements)

References 105 publications

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“…Nowadays, both MMF and rituximab are valuable agents Fig. 3 Calcium and vitamin D diagnostics and supplementation at presentation in the treatment of SDNS [21,23]. Variation was present among our respondents on the rituximab regimen used.…”

Section: Discussionmentioning

confidence: 91%

“…Most pediatric nephrologists and pediatricians indicated that MMF was their preferred choice, with CNI as a second choice. The preferred choice of MMF is most likely based on a favorable side effect profile compared to CNI with the potential nephrotoxic effects being the most important limitation for CNI use [ 21 , 22 ]. Rituximab was also considered by the Dutch pediatric nephrologists for the treatment of FRNS and SDNS.…”

Section: Discussionmentioning

confidence: 99%

“…The 2012 KDIGO Clinical Practice Guideline previously stated that in children with FRNS and SDNS, there is low-quality evidence to support the use of MMF, and even very low-quality evidence for rituximab [ 13 ]. Nowadays, both MMF and rituximab are valuable agents in the treatment of SDNS [ 21 , 23 ]. Variation was present among our respondents on the rituximab regimen used.…”

Section: Discussionmentioning

confidence: 99%

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Practice variations in the management of childhood nephrotic syndrome in the Netherlands

et al. 2021

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Nephrotic syndrome in childhood is a common entity in the field of pediatric nephrology. The optimal treatment of children with nephrotic syndrome is often debated. Previously conducted studies have shown significant variability in nephrotic syndrome management, especially in the choice of steroid-sparing drugs. In the Netherlands, a practice guideline on the management of childhood nephrotic syndrome has been available since 2010. The aim of this study was to identify practice variations and opportunities to improve clinical practice of childhood nephrotic syndrome in the Netherlands. A digital structured survey among Dutch pediatricians and pediatric nephrologists was performed, including questions regarding the initial treatment, relapse treatment, kidney biopsy, additional immunosuppressive treatment, and supportive care. Among the 51 responses, uniformity was seen in the management of a first presentation and first relapse. Wide variation was found in the tapering of steroids after alternate day dosing. Most pediatricians and pediatric nephrologists (83%) would perform a kidney biopsy in case of steroid-resistant nephrotic syndrome, whereas for frequent relapsing and steroid-dependent nephrotic syndrome this was 22% and 41%, respectively. Variation was reported in the steroid-sparing treatment. Finally, significant differences were present in the supportive treatment of nephrotic syndrome.Conclusion: Substantial variation was present in the management of nephrotic syndrome in the Netherlands. Differences were identified in steroid tapering, use of steroid coverage during stress, choice of steroid-sparing agents, and biopsy practice. To promote guideline adherence and reduce practice variation, factors driving this variation should be assessed and resolved. What is Known:• National and international guidelines are available to guide the management of childhood nephrotic syndrome.• Several aspects of the management of childhood nephrotic syndrome, including the choice of steroid-sparing drugs and biopsy practice, are controversial and often debated among physicians.What is New:• Significant practice variation is present in the management of childhood nephrotic syndrome in the Netherlands, especially in the treatment of FRNS, SDNS, and SRNS.• The recommendation on the steroid treatment of a first episode of nephrotic syndrome in the KDIGO guideline leaves room for interpretation and is likely the cause of substantial differences in steroid-tapering practices among Dutch pediatricians and pediatric nephrologists.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Practice variations in the management of childhood nephrotic syndrome in the Netherlands

et al. 2021

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“…Whilst idiopathic nephrotic syndrome in children usually responds well to corticosteroid treatment, more than two thirds of patients experience relapses and 30% develop a complicated course with frequent relapses or steroid dependency (SDNS) [1][2][3][4][5][6][7]. Relapses may lead to serious complications from anasarca, infections, thrombosis and malnutrition.…”

Section: Introductionmentioning

confidence: 99%

“…Relapses may lead to serious complications from anasarca, infections, thrombosis and malnutrition. Repeated or even continuous steroid treatment leads to considerable medication related toxicity and morbidity [1][2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome

et al. 2020

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Background Approximately 30% of children with idiopathic nephrotic syndrome develop a complicated course with frequent relapses or steroid dependency. Rituximab, a B cell depleting monoclonal antibody, is a safe and effective alternative to steroids or other immunosuppressants for achieving and maintaining remission in this population at short term. Despite the good initial response relapses inevitably occur after regeneration of B lymphocytes, necessitating either repeat courses of rituximab or addition of another steroid-sparing immunosuppressant. Methods This is a prospective, single-center, open-label, two-parallel-arm randomized controlled phase III study among children with steroid dependent nephrotic syndrome who are maintained in remission with oral steroids. One hundred children will be randomized to either Rituximab and maintenance Mycophenolate mofetil (A) or repeated courses of prophylactic Rituximab only (B). In arm A, mycophenolate mofetil (1200 mg/m2 per day) will be started 3 months after Rituximab administration. In arm B, Rituximab infusions will be administered at 0, 8 and 16 months if B cell count normalize at the given time points. Prednisolone will be discontinued in both groups 2 weeks following first course of rituximab. Primary aim is to evaluate the difference in 24-month relapse-free survival. Main secondary endpoints are cumulative prednisolone dose, frequency of relapses and changes in anthropometry. Circulating B lymphocyte populations will be studied as biomarkers or predictors of rituximab responsiveness and adverse events will be analysed. Discussion The study will provide evidence as to the comparative safety and efficacy of two alternative steroid-sparing therapeutic options in children suffering from steroid dependent nephrotic syndrome. The two-year study design will address the long-term results obtained with the alternative treatment protocols. Trial registration This trial was prospectively registered to the Clinicaltrial.gov (NCT03899103 dated 02/04/2019; https://clinicaltrials.gov/) and Clinical Trials Registry of India (CTRI/2019/04/018517 dated 09/04/2019).

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Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome

et al. 2018

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IMPORTANCE Calcineurin inhibitors are an established first-line corticosteroid-sparing therapy for patients with corticosteroid-dependent nephrotic syndrome (CDNS), whereas B-lymphocyte-depleting therapy is mostly used as a rescue for calcineurin inhibitor-resistant cases. The positive efficacy and safety profile of rituximab raises the question of whether it could be used as a first-line alternative to calcineurin inhibitor therapy. OBJECTIVE To compare the efficacy of rituximab and tacrolimus in maintaining relapse-free survival among children with CDNS. DESIGN, SETTING, AND PARTICIPANTS A parallel-arm, open-label, randomized clinical trial was performed from May 8, 2015, to September 20, 2016, with 1-year follow-up in a single-center, tertiary care unit. A total of 176 consecutive children aged 3 to 16 years with CDNS not previously treated with corticosteroid-sparing agents were screened for eligibility. INTERVENTIONS The children received either tacrolimus (along with tapering alternate-day prednisolone) for 12 months or a single course of rituximab (2 infusions of 375 mg/m 2). MAIN OUTCOMES AND MEASURES Twelve-month relapse-free survival in the intention-to-treat population. RESULTS Of the 176 children screened for eligibility, 120 were randomized and all but 3 patients completed 1 year of follow-up. The groups were comparable, with mean (SD) age of 7.2 (2.8) years, 32 boys (53.3%) in each group, mean (SD) disease duration of 2.5 (1.5) years and 2.3 (1.7) in the tacrolimus and rituximab groups, respectively, disease duration less than 1 year among 15 children (25.0%) in each group, median (interquartile range) of 4 (3-5) relapses in each group, and mean (SD) cumulative prednisolone dose of 246 (48) mg/kg and 239 (52) mg/kg in the prestudy year in the tacrolimus and rituximab groups, respectively. Rituximab therapy was associated with a higher 12-month relapse-free survival rate than tacrolimus (54 [90.0%] vs 38 [63.3%] children; P < .001; odds ratio, 5.21; 95% CI, 1.93-14.07). Among the patients who experienced relapse, median time to first relapse was 40 weeks in the rituximab group and 29 weeks in the tacrolimus group. Only 2 patients in the rituximab group had more than 1 relapse during the study period compared with 10 patients in the tacrolimus group. The cumulative corticosteroid dose during the 12-month study period was lower with rituximab compared with tacrolimus (mean [SD], 25.8 [27.8] vs 86.3 [58.0] mg/kg). Although both treatments were well tolerated, mild to moderate infections were twice as common in the tacrolimus group (26 [43.3%] vs 13 [21.7%] events). CONCLUSIONS AND RELEVANCE In children with CDNS, rituximab appears to be more effective than tacrolimus in maintaining disease remission and minimizing corticosteroid exposure and, given its good tolerability and lack of nephrotoxic effects, may be considered as first-line corticosteroid-sparing therapy.

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Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children

Cited by 69 publications

References 105 publications

Practice variations in the management of childhood nephrotic syndrome in the Netherlands

Practice variations in the management of childhood nephrotic syndrome in the Netherlands

Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome

Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome

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