Steroid-sensitive nephrotic syndrome: an evidence-based update of immunosuppressive treatment in children

2015 ◽  
Vol 101 (4) ◽  
pp. 404-408 ◽  
Author(s):  
Nicholas Larkins ◽  
Siah Kim ◽  
Jonathan Craig ◽  
Elisabeth Hodson
Keyword(s):  
Nephrotic Syndrome ◽  
Immunosuppressive Agents ◽  
Immunosuppressive Treatment ◽  
Current Evidence ◽  
Upper Respiratory Tract ◽  
Glomerular Diseases ◽  
Steroid Dependent ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive ◽  
Risk Of Relapse

Nephrotic syndrome is one of the most common paediatric glomerular diseases, with an incidence of around two per 100 000 children per year. Corticosteroids are the mainstay of treatment, with 85%–90% of children going into remission with an 8-week course of treatment. Unfortunately, nephrotic syndrome follows a relapsing and remitting course in the majority, with 90% relapsing at least once. About half will progress to frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Different initial steroid regimens have been evaluated since the first trials in Europe and America in the 1960s. Most trials have been designed to evaluate the optimal duration of the initial therapy, rather than different cumulative doses of corticosteroid, or the management of relapses. Until recently, these data suggested that an initial treatment duration of up to 6 months reduced the number of children developing a relapse, without evidence of increased steroid toxicity. Recently, three large, well-designed randomised control trials were published, which demonstrated no significant reduction in risk of relapse or of developing FRNS by extended treatment compared with 2 or 3 months. While there are few trial data to guide the treatment of individual relapses in steroid-sensitive nephrotic syndrome (SSNS), there is some evidence that a short course of corticosteroid therapy during upper respiratory tract infection may prevent relapse. In patients with FRNS or SDNS who continue to relapse despite low-dose alternate-day steroids a number of non-corticosteroid, steroid-sparing immunosuppressive agents (cyclophosphamide, ciclosporin, tacrolimus, mycophenolate mofetil, levamisole, rituximab) have been shown to reduce the risk of relapse and of FRNS. However, there are limited head-to-head data to inform which agent should be preferred. In this article, we review recent data from randomised trials to update paediatricians on the current evidence supporting interventions in SSNS.

scholarly journals Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation

BMJ ◽  
2019 ◽  
pp. l1800 ◽  
Author(s):  
Nicholas J A Webb ◽  
Rebecca L Woolley ◽  
Tosin Lambe ◽  
Emma Frew ◽  
Elizabeth A Brettell ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Confidence Interval ◽  
Immunosuppressive Treatment ◽  
Phase Iii ◽  
Prednisolone Treatment ◽  
Steroid Dependent ◽  
Life Years ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive ◽  
Extended Course

Abstract Objective To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. Design Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. Setting 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. Participants 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. Interventions Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m 2 ) or a standard eight week course of prednisolone (total dose 2240 mg/m 2 ). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). Main outcome measures The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. Results No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval −0.005 to 0.037) and cost savings (difference −£1673 ($2160; €1930), 95% confidence interval −£3455 to £109). Conclusions Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. Trial registration ISRCTN16645249; EudraCT 2010-022489-29.

scholarly journals Levamisole in Children with Idiopathic Nephrotic Syndrome: Clinical Efficacy and Pathophysiological Aspects

2019 ◽  
Vol 8 (6) ◽  
pp. 860 ◽  
Author(s):  
Anne K. Mühlig ◽  
Jun Young Lee ◽  
Markus J. Kemper ◽  
Andreas Kronbichler ◽  
Jae Won Yang ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Idiopathic Nephrotic Syndrome ◽  
Low Frequency ◽  
Glomerular Diseases ◽  
Steroid Dependency ◽  
Randomized Controlled ◽  
Steroid Dependent ◽  
Frequent Relapses ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

Steroid sensitive nephrotic syndrome is one of the most common pediatric glomerular diseases. Unfortunately, it follows a relapsing and remitting course in the majority of cases, with 50% of all cases relapsing once or even more often. Most children with idiopathic nephrotic syndrome respond initially to steroid therapy, nevertheless repeated courses for patients with relapses induce significant steroid toxicity. Patients with frequent relapses or steroid dependency thus require alternative treatment, such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, levamisole, or rituximab. To reduce the relapse rate, several drugs have been used. Among these, levamisole has been considered the least toxic and least expensive therapy. Several randomized controlled trials (RCT) showed that levamisole is effective in reducing the relapse risk in steroid sensitive forms of nephrotic syndrome with a low frequency of side effects. Levamisole is a synthetic imidazothiazole derivative with immune-modulatory properties. In this article, we review recent data from randomized trials and observational studies to assess the efficacy of levamisole in frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome.

scholarly journals Association of HLA class II and history of atopy and frequent relapse of childhood steroid-sensitive nephrotic syndrome

2007 ◽  
Vol 47 (2) ◽  
pp. 60 ◽  
Author(s):  
Dany Hilmanto
Keyword(s):  
Nephrotic Syndrome ◽  
Class Ii ◽  
Hla Class Ii ◽  
Healthy Children ◽  
Upper Respiratory Tract ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
History Of ◽  
Steroid Sensitive ◽  
Polymerase Chain ◽  
Control Study

Background The association between HLA class II and frequentrelapse of nephrotic syndrome (FRNS) has been reported.Objective To identify the association between HLA class II,history of atopy, and upper respiratory tract infection (URTI)with FRNS.Methods This was a case control study conducted at theDepartment of Child Health, Hasan Sadikin Hospital Bandungand Cipto Mangunkusumo Hospital Jakarta from November 2002to October 2003 on children aged 1-14 years with FRNS. Thesubjects consisted of 40 FRNS and 84 healthy children. HLAclass II was typed by polymerase chain reaction-sequence specificoligonucleotide (PCR-SSO) in Leiden, the Netherlands. Theassociation between HLA class II and FRNS was expressed byodds ratio (OR). The association between such factors and FRNSwas analyzed by logistic regression.Results Atopy was higher in patients than that in controls(P=0.013). URTI did not differ in both groups (P=0.173). HLA-DRB1*03 and DRB1*04 (OR=4.43, P=0.03), DQB1*02(OR=3.43, P=0.00), and DQB1*04 (OR=12.06, P=0.01) weresignificantly higher among patients than those in controls whereasHLA-DRB1*12 (OR=0.34, P=0.02) and DQB1*0301p(OR=0.35, P=0.02) were significantly lower among patients thanthose in controls. Using logistic regression analysis, only HLA-DRB1*12, DQB1*02 and atopy took part in FRNS.Conclusion HLA-DRB1*12, DQB1*02, and atopy all togetherhave association with FRNS.

scholarly journals HUBUNGAN ASPEK KLINIS DAN LABORATORIUM DENGAN TIPE SINDROM NEFROTIK PADA ANAK

e-CliniC ◽  
2016 ◽  
Vol 4 (1) ◽  
Author(s):  
Robin Samuel Mamesah ◽  
Adrian Umboh ◽  
Stevanus Gunawan
Keyword(s):  
Blood Pressure ◽  
Nephrotic Syndrome ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Glomerular Diseases ◽  
Steroid Resistant ◽  
Cholesterol Levels ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive ◽  
The Relationship

Abstract: Nephrotic Syndrome (NS) is one of the most frequent glomerular diseases in children marked with proteinuria, hypoalbuminaemia, and edema with or without hypercholesterolemia. Approximately there are six cases of NS per year every 100.000 child aged less than 14 years old in Indonesia with ratio between males and females 2:1. Based on therapy, NS is categorized into Steroid Sensitive Nephrotic Syndrome (SSNS) and Steroid Resistant Nephrotic Syndrome (SRNS). This study aimed to obtain the relationship between clinical and laboratory aspects with NS type in children. This was a retrospective analytical study conducted by using SSNS and SRNS patient data of the medical record in Department of Pediatric Prof. Dr. R. D. Kandou Hospital Manado. Daya were categorized into identity, age, blood pressure, proteinuria, hematuria, as well as albumin and cholesterol levels. The results showed that there were 29 SN patients (18 patients of SSNS and 11 patients of SRNS) consisted of 17 males (59%) and 12 females (41%). The statistical analysis showed that there was no significant correlation among sex (p=0.064), age (p=0.064), edema (p=0.138), systolic pressure (0.283), diastolic pressure (p=0.701), proteinuria (p=0.999), hematuria (p=0.060), albumin (p=0.175), and cholesterol (p=0.814) in both of SSNS and SRNS patients. Conclusion: There was no relationship between sex, age, blood pressure, proteinuria, hematuria, albumin, and cholesterol related to SSNS and SRNS. Keywords: nephrotic syndrome, proteinuria, SSNS, SRNS Abstrak: Sindrom nefrotik (SN) adalah salah satu penyakit glomerulus yang sering ditemukan pada anak, yang ditandai dengan proteinuria, hipoalbuminemia, dan edema dengan atau tanpa hiperkolesterolemia. Diperkirakan enam kasus per tahun tiap 100.000 anak kurang dari 14 tahun di Indonesia dengan perbandingan antara laki-laki dan perempuan 2:1. Sindrom nefrotik berdasarkan respon terapinya terbagi menjadi sindrom nefrotik sensitif steroid (SNSS) dan sindrom nefrotik resisten steroid (SNRS). Penelitian ini bertujuan untuk mengetahui hubungan aspek klinis dan laboratorium dengan tipe SN pada anak. Jenis penelitian ini analitik retrospektif pada pasien SNSS dan SNRS berdasarkan data rekam medik di Bagian Ilmu Kesehatan Anak RSUP Prof. Dr. R. D. Kandou Manado. Data dikumpulkan meliputi identitas, usia, tekanan darah, proteinuria, edema, hematuria, hematuria, serta kadar albumin dan kolesterol. Hasil penelitian memperlihatkan 29 pasien SN terdiri dari 18 pasien SNSS dan 11 pasien SNRS. Laki-laki sebanyak 17 kasus (59%) dan perempuan 12 kasus (41%). Tidak didapatkan hubungan pada jenis kelamin (p=0,064), usia (p=0,064), edema (p=0,138), tekanan darah sistolik (p=0,283), tekanan darah diastolik (p=0,701), proteinuria (p=0,999), hematuria (p=0,060), albumin (p=0,175), kolesterol (p=0,814) pada kedua kelompok. Simpulan: Tidak terdapat hubungan antara jenis kelamin, usia, tekanan darah, proteinuria, hematuria albumin dan kolesterol dengan SNSS dan SNRS.Kata kunci: sindrom nefrotik, proteinuria, SNSS, SNRS.

scholarly journals Therapies for Glomerular Diseases in Children

2018 ◽  
Vol 54 (01) ◽  
pp. 043-053
Author(s):  
Arvind Bagga
Keyword(s):  
Nephrotic Syndrome ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Steroid Resistance ◽  
Glomerular Diseases ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Dependence ◽  
Frequent Relapses ◽  
Steroid Sensitive

AbstractNephrotic syndrome is an important chronic disease of childhood, with a steroid sensitive course in most patients. Research on pathogenesis has emphasized the importance of T-lymphocyte dysregulation and vascular permeability factors that alter podocyte function and glomerular permselectivity. Mutations in genes that encode important podocyte proteins and therapeutic targets within podocytes have been identified. A hypothesis unifying available evidence on pathogenesis is yet to be proposed. An important proportion of patients have difficult disease course, characterized by frequent relapses, steroid dependence or steroid resistance, requiring therapy with alternative immunosuppressive agents. Clinical studies support the use of levamisole, cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors (CNIs) and rituximab in patients with frequent relapses or steroid dependence. The management of steroid-resistant nephrotic syndrome is difficult and patients failing to achieve remission show progressive renal damage. Prospective studies in patients with steroid sensitive and steroid resistant nephrotic syndrome are the basis of current guidelines while ongoing studies will help identify and formulate effective and safe therapies.

scholarly journals Cyclophosphamide in frequent-relapsing or steroid-dependent nephrotic syndrome: Review of 38 patients

2016 ◽  
Vol 45 (1) ◽  
pp. 18
Author(s):  
Yulia Iriani ◽  
Taralan Tambunan ◽  
Sudigdo Sastroasmoro
Keyword(s):  
Nephrotic Syndrome ◽  
Cyclophosphamide Therapy ◽  
Steroid Dependent ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive ◽  
The Mean ◽  
One Year ◽  
Steroid Dependent Nephrotic Syndrome ◽  
Better Than

Background Steroid-sensitive nephrotic syndrome (SSNS) in chil-dren is characterized by relapsing courses in a substantial propor-tion of affected individuals. Children with frequent-relapsing neph-rotic syndrome (FRNS) or steroid-dependent nephrotic syndrome(SDNS) are at risk of severe steroid toxicity and need individual-ized treatment. Previous studies have elucidated that cyclophos-phamide (CPA) reduced the risk of relapses and increased thelength of subsequent remissions in children with relapsing SSNS.Methods This retrospective study evaluated 38 patients (26 FRNSand 12 SDNS) after cyclophosphamide therapy to elucidate theefficacy of CPA in FRNS or SDNS in the Department of Child Health,Cipto Mangunkusumo Hospital. All patients were treated with CPA(2 mg/kg per day) for 8 weeks, in combination with prednisone.Results The median (range) duration of follow up was 45 months(24-140 months) for FRNS and 29 months (24-63 months) forSDNS. The mean relapse rate one year prior to CPA therapy inFRNS and SDNS were 3.8 relapses/year (95%CI 3.4; 4.2) and 4.0relapses/year (95%CI 3.3; 4.7), which were reduced to 1.6 relapses/year (95% CI 1.1; 2.1) and 2.3 relapses/year (95%CI 1.5;3.2), re-spectively. The overall rate of cumulative sustained good response(complete remission or infrequent relapses) was 65% after 36months. Frequent relapsing versus steroid-dependent status wassignificantly correlated with rate of sustained good response after36 months (85% versus 15%) with OR=23 (95%CI 3.1;225.2).Conclusion The efficacy of cyclophosphamide therapy in themanagement of FRNS is better than in SDNS

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