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Meta-Analysis
. 2020 Aug 31;2020(8):CD001533.
doi: 10.1002/14651858.CD001533.pub6.

Corticosteroid therapy for nephrotic syndrome in children

Deirdre Hahn  1 , Susan M Samuel  2 , Narelle S Willis  3   4 , Jonathan C Craig  4   5 , Elisabeth M Hobson  3   4
Affiliations
Meta-Analysis

Corticosteroid therapy for nephrotic syndrome in children

Deirdre Hahn et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: In nephrotic syndrome protein leaks from blood into the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. While most children with nephrotic syndrome respond to corticosteroids, 80% experience a relapsing course. Corticosteroids have reduced the death rate to around 3%. However, corticosteroids have well recognised potentially serious adverse effects such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis, and behavioural disturbances. This is an update of a review first published in 2000 and updated in 2002, 2005, 2007, and 2015.

Objectives: The aim of this review was to assess the benefits and harms of different corticosteroid regimens in children with steroid-sensitive nephrotic syndrome (SSNS). The benefits and harms of therapy were studied in two groups of children 1) children in their initial episode of SSNS, and 2) children who experience a relapsing course of SSNS.

Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 30 May 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: Randomised controlled trials (RCTs) performed in children (one to 18 years) in their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent.

Data collection and analysis: Two authors independently assessed risk of bias and extracted data. Results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).

Main results: In this 2020 review update 16 new included studies were identified providing a total of 48 included studies with 3941 randomised participants. Risk of bias methodology was often poorly performed with only 25 studies and 22 studies respectively assessed to be at low risk for random sequence generation and allocation concealment. Only nine studies (19%) were at low risk of bias for performance (blinding of participants and personnel) and 11 studies were at low risk of detection bias (blinding of outcome assessment); nine of these studies were placebo-controlled RCTs. Twenty-two studies (fewer than 50%) were at low risk for attrition bias and 23 studies were at low risk for reporting bias (selective outcome reporting). In seven studies, which evaluated children in their initial episode of SSNS and were at low risk of bias for selection bias, there is little or no difference in the number of children with frequent relapses when comparing two months of prednisone with three months or more (RR 0.99, 95% CI 0.82 to 1.19; 585 participants, 4 studies; I2 = 0%) or when comparing three months with five to seven months of therapy (RR 0.99, 95% CI 0.74 to 1.33; 376 participants, 3 studies; I2 = 35%; high certainty evidence). In analyses of eight studies at low risk of selection bias, there is little or no difference in the number of children with any relapse by 12 to 24 months when comparing two months of prednisone with three months or more (RR 0.91, 95% CI 0.78 to 1.06; 637 participants; 5 studies; I2 = 47%) or when comparing three months with five to seven months of therapy (RR 0.88, 95% CI 0.70 to 1.11; 377 participants, 3 studies; I2 = 53%). Little or no difference was noted in adverse effects between the different treatment durations. Among children with relapsing SSNS, two small studies showed that time to remission did not differ between prednisone doses of 1 mg/kg compared with the conventional dose of 2 mg/kg (MD 0.71 days, 95% CI -0.43 to 1.86; 79 participants) and that the total prednisone dose administered was lower (MD -20.60 mg/kg, 95% CI -25.65 to -15.55; 20 participants). Two studies found little or no difference in the number with relapse at six months when comparing dosing by weight with dosing by surface area (RR 1.03, 95% CI 0.71 to 1.49; 146 participants). One study found a reduced risk of relapse with low daily dosing compared with alternate daily dosing (MD -0.90 number of relapses/year, 95% CI -1.33 to -0.47). Four studies found that in children with frequently relapsing disease, daily prednisone during viral infections compared with alternate-day prednisone or no treatment reduced the risk of relapse.

Authors' conclusions: There are now four well designed studies randomising 823 children which have clearly demonstrated that there is no benefit of prolonging prednisone therapy beyond two to three months in the first episode of SSNS. Small studies in children with relapsing disease have identified no differences in the times to remission using half the conventional induction dose of 2 mg/kg or 60 mg/m2. It is imperative that a much larger study be carried out to confirm these findings. Lower dose prednisone therapy administered daily during an upper respiratory infection or other infection reduces the risk of relapse compared with continuing alternate-day prednisone or no prednisone based on four small studies. The results of a much larger RCT enrolling more than 300 children are awaited to determine the relative efficacies and adverse effects of using alternate-day compared with daily prednisone to prevent relapse in children with intercurrent infections.

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Conflict of interest statement

  1. Deirdre Hahn: none known

  2. Susan Samuel: none known

  3. Narelle Willis: none known

  4. Jonathan Craig: none known

  5. Elisabeth Hodson: none known

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Steroid therapy in first episode: ≥ 3 months versus 2 months therapy, outcome: 1.3 Number with frequent relapses by 12 to 24 months stratified by risk of bias for selection bias.
5
5
Forest plot of comparison: 2 Steroid therapy in first episode: 5 to 7 months versus 3 months, outcome: 2.3 Number with frequent relapses stratified by risk of selection bias.
1.1
1.1. Analysis
Comparison 1: Steroid therapy in first episode: ≥ 3 months versus 2 months therapy, Outcome 1: Number with frequent relapses by 12 to 24 months
1.2
1.2. Analysis
Comparison 1: Steroid therapy in first episode: ≥ 3 months versus 2 months therapy, Outcome 2: Number of children relapsing by 12 to 24 months
1.3
1.3. Analysis
Comparison 1: Steroid therapy in first episode: ≥ 3 months versus 2 months therapy, Outcome 3: Number with frequent relapses by 12 to 24 months stratified by risk of bias for selection bias
1.4
1.4. Analysis
Comparison 1: Steroid therapy in first episode: ≥ 3 months versus 2 months therapy, Outcome 4: Number of children relapsing by 12 to 24 months stratified by risk of selection bias
1.5
1.5. Analysis
Comparison 1: Steroid therapy in first episode: ≥ 3 months versus 2 months therapy, Outcome 5: Adverse events
2.1
2.1. Analysis
Comparison 2: Steroid therapy in first episode: 5 to 7 months versus 3 months, Outcome 1: Number with frequent relapses by 12 to 24 months
2.2
2.2. Analysis
Comparison 2: Steroid therapy in first episode: 5 to 7 months versus 3 months, Outcome 2: Number of children relapsing by 12 to 24 months
2.3
2.3. Analysis
Comparison 2: Steroid therapy in first episode: 5 to 7 months versus 3 months, Outcome 3: Number with frequent relapses stratified by risk of selection bias
2.4
2.4. Analysis
Comparison 2: Steroid therapy in first episode: 5 to 7 months versus 3 months, Outcome 4: Number of children relapsing by 12 to 24 months stratified by risk of selection bias
2.5
2.5. Analysis
Comparison 2: Steroid therapy in first episode: 5 to 7 months versus 3 months, Outcome 5: Adverse events
3.1
3.1. Analysis
Comparison 3: Steroid therapy in the first episode: 1 month versus 2 months therapy, Outcome 1: Number of children relapsing by 6 to 12 months
3.2
3.2. Analysis
Comparison 3: Steroid therapy in the first episode: 1 month versus 2 months therapy, Outcome 2: Number of children relapsing by 12 to 24 months
3.3
3.3. Analysis
Comparison 3: Steroid therapy in the first episode: 1 month versus 2 months therapy, Outcome 3: Number with frequent relapses
4.1
4.1. Analysis
Comparison 4: Steroid therapy in the first episode: 12 months versus 5 months therapy, Outcome 1: Number with relapse
5.1
5.1. Analysis
Comparison 5: Steroid therapy in the first episode of nephrotic syndrome: different total doses given over the same duration, Outcome 1: Relapse at 12 months
5.2
5.2. Analysis
Comparison 5: Steroid therapy in the first episode of nephrotic syndrome: different total doses given over the same duration, Outcome 2: Number with FRNS
5.3
5.3. Analysis
Comparison 5: Steroid therapy in the first episode of nephrotic syndrome: different total doses given over the same duration, Outcome 3: Adverse effects
6.1
6.1. Analysis
Comparison 6: Methylprednisolone in steroid therapy in first episode of nephrotic syndrome: methylprednisone versus prednisolone, Outcome 1: Time to remission
6.2
6.2. Analysis
Comparison 6: Methylprednisolone in steroid therapy in first episode of nephrotic syndrome: methylprednisone versus prednisolone, Outcome 2: Number with relapse
7.1
7.1. Analysis
Comparison 7: Daily prednisolone treatment during viral infections, Outcome 1: Number with relapse with infection
7.2
7.2. Analysis
Comparison 7: Daily prednisolone treatment during viral infections, Outcome 2: Number of relapses/patient
7.3
7.3. Analysis
Comparison 7: Daily prednisolone treatment during viral infections, Outcome 3: Number of relapses/patient at 2 years
8.1
8.1. Analysis
Comparison 8: Deflazacort versus prednisolone, Outcome 1: Number with remission
8.2
8.2. Analysis
Comparison 8: Deflazacort versus prednisolone, Outcome 2: Number of children with relapse by 9 to 12 months
9.1
9.1. Analysis
Comparison 9: Treatment therapy (various) versus standard therapy in relapsing nephrotic syndrome, Outcome 1: Number of children relapsing during therapy
9.2
9.2. Analysis
Comparison 9: Treatment therapy (various) versus standard therapy in relapsing nephrotic syndrome, Outcome 2: Number of children with relapses by 9 to 12 months
9.3
9.3. Analysis
Comparison 9: Treatment therapy (various) versus standard therapy in relapsing nephrotic syndrome, Outcome 3: Mean time to relapse
9.4
9.4. Analysis
Comparison 9: Treatment therapy (various) versus standard therapy in relapsing nephrotic syndrome, Outcome 4: Mean relapse rate/patient/year
9.5
9.5. Analysis
Comparison 9: Treatment therapy (various) versus standard therapy in relapsing nephrotic syndrome, Outcome 5: Cumulative steroid dose
9.6
9.6. Analysis
Comparison 9: Treatment therapy (various) versus standard therapy in relapsing nephrotic syndrome, Outcome 6: Mean time to remission
9.7
9.7. Analysis
Comparison 9: Treatment therapy (various) versus standard therapy in relapsing nephrotic syndrome, Outcome 7: Serious adverse events
10.1
10.1. Analysis
Comparison 10: Steroid therapy for relapse: different prednisone doses, Outcome 1: Time to remission with different prednisone doses
10.2
10.2. Analysis
Comparison 10: Steroid therapy for relapse: different prednisone doses, Outcome 2: Cumulative prednisone dose to achieve remission
10.3
10.3. Analysis
Comparison 10: Steroid therapy for relapse: different prednisone doses, Outcome 3: Number with relapse
11.1
11.1. Analysis
Comparison 11: Daily versus alternate‐day prednisone for relapsing nephrotic syndrome, Outcome 1: Number of relapses in 12 months
11.2
11.2. Analysis
Comparison 11: Daily versus alternate‐day prednisone for relapsing nephrotic syndrome, Outcome 2: Adverse effects
12.1
12.1. Analysis
Comparison 12: Weight‐based versus body surface area (BSA)‐based dosing of prednisolone, Outcome 1: Relapse at 6 months
12.2
12.2. Analysis
Comparison 12: Weight‐based versus body surface area (BSA)‐based dosing of prednisolone, Outcome 2: Adverse effects
12.3
12.3. Analysis
Comparison 12: Weight‐based versus body surface area (BSA)‐based dosing of prednisolone, Outcome 3: Prednisone dose
13.1
13.1. Analysis
Comparison 13: Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 1: Number with relapses
13.2
13.2. Analysis
Comparison 13: Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 2: Relapse rate/patient/year
13.3
13.3. Analysis
Comparison 13: Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 3: Number with FRNS or SDNS
13.4
13.4. Analysis
Comparison 13: Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 4: Cumulative steroid dose
13.5
13.5. Analysis
Comparison 13: Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 5: Adverse effects
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Update of

References

References to studies included in this review

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Ekka 1997 {published data only}
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    1. Paul SK, Muinuddin G, Jahan S, Begum A, Rahman MH, Hossain MM. Long versus standard initial prednisolone therapy in children with idiopathic nephrotic syndrome. Mymensingh Medical Journal: MMJ 2014;23(2):261-7. [MEDLINE: ] - PubMed
Pecoraro 2003 {published data only}
    1. Pecoraro C, Caropreso MR, Malgieri G, Ferretti A, Nuzzi F. Therapy of first episode steroid responsive nephrotic syndrome (FESRNS): a randomised controlled trial [abstract no: MP087]. Nephrology Dialysis Transplantation 2005;20(Suppl 5):v230. [CENTRAL: CN-00644161]
    1. Pecoraro C, Caropreso MR, Malgieri G, Ferretti AV, Raddi G, Piscitelli A, et al. Therapy of first episode of steroid responsive nephrotic syndrome: a randomised controlled trial [abstract no: OFC41]. Pediatric Nephrology 2004;19(9):C72. [CENTRAL: CN-00644160]
    1. Pecoraro C, Caropreso MR, Passaro G, Ferretti AV, Malgieri G. Therapy of first episode of steroid responsive nephrotic syndrome: a randomised controlled trial [abstract no: M199]. Nephrology Dialysis Transplantation 2003;18(Suppl 4):63. [CENTRAL: CN-00447140]
PREDNOS 2019 {published data only}16645249
    1. Webb N, Trompeter R, Cummins C, Wheatley K, Frew E. Long-term tapering versus standard prednisolone (steroid) therapy for the treatment of the initial episode of childhood nephrotic syndrome: national multicentre randomised double blind trial [protocol]. PREDNOS Clinical Trial Protocol Version 2.1 2013 Sept 1.
    1. Webb N, Wooley R, Brettell E, Cummins C, Trompeter R, Barsoum E, et al. Standard vs extended course prednisolone therapy for the presenting episode of steroid sensitive nephrotic syndrome: the PREDNOS study [abstract no: O-08]. Pediatric Nephrology 2017;32(9):1647-8. [EMBASE: 618119435]
    1. Webb NJ, Woolley RL, Lambe T, Frew E, Brettell EA, Barsoum EN, et al. Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation. BMJ 2019;365:l1800. [MEDLINE: ] - PMC - PubMed
    1. Webb NJ, Woolley RL, Lambe T, Frew E, Brettell EA, Barsoum EN, et al. Sixteen-week versus standard eight-week prednisolone therapy for childhood nephrotic syndrome: the PREDNOS RCT. Health Technology Assessment (Winchester, England) 2019;23(26):1-108. [MEDLINE: ] - PMC - PubMed
PREDNOS PILOT 2019 {published data only}
    1. Webb NJ, Woolley RL, Lambe T, Frew E, Brettell EA, Barsoum EN, et al. Sixteen-week versus standard eight-week prednisolone therapy for childhood nephrotic syndrome: the PREDNOS RCT. Health Technology Assessment (Winchester, England) 2019;23(26):1-108. [MEDLINE: ] - PMC - PubMed
PROPINE 2018 {published data only}
    1. Gargiulo A, Vivarelli M, Pecoraro C, Pennesi M, Pasini A, Edefonti A, et al. Short versus long courses of prednisone for the treatment of relapses of steroid sensitive nephrotic syndrome. results of the PROPINE study [abstract no: O-4]. Pediatric Nephrology 2018;33(10):1810. [EMBASE: 618119435]
Raman 2016 {published data only}
    1. Raman V, Krishnamurthy S, Harichandrakumar KT. Body weight-based prednisolone versus body surface area-based prednisolone regimen for induction of remission in children with nephrotic syndrome: a randomized, open-label, equivalence clinical trial. Pediatric Nephrology 2016;31(4):595-604. [MEDLINE: ] - PubMed
Satomura 2001 {published data only}
    1. Satomura K, Yamaoka K, Shima M, Tanaka Y, Ashino N, Nakagawa K, et al. Standard vs low initial dose of prednisolone therapy for first episodes of nephrotic syndrome in children [abstract no: P238]. Pediatric Nephrology 2001;16(8):C117. [CENTRAL: CN-00447593]
Sharma 2002 {unpublished data only}
    1. Gulati S, Ahmed M, Sharma RK, Gupta A, Pokhariyal S. Comparison of abrupt withdrawal versus slow tapering regimen of prednisolone therapy in the management of first episode of steroid responsive childhood idiopathic nephrotic syndrome [abstract]. Nephrology Dialysis Transplantation 2001;16(6):A87. [CENTRAL: CN-00445595]
    1. Sharma RK, Ahmed M, Gulati S, Gupta A, Pokhariyal S. Comparison of abrupt withdrawal versus slow tapering regimen of prednisolone therapy in the management of first episode of steroid responsive childhood idiopathic nephrotic syndrome. Data on file 2002.
    1. Sharma RK, Ahmed M, Gupta A, Gulati S, Sharma AP. Comparison of abrupt withdrawal versus slow tapering regimens of prednisolone therapy in management of first episode of steroid responsive childhood idiopathic nephrotic syndrome [abstract]. Journal of the American Society of Nephrology 2000;11(Sept):97A. [CENTRAL: CN-00550434]
Sheikh 2019 {published data only}
    1. Sheikh S, Mishra K, Kumar M. Low versus conventional dose prednisolone for nephrotic syndrome relapses: randomised-controlled, non-inferiority-trial [abstract no: IPN10923-86]. Pediatric Nephrology 2019;34(10):1980. - PubMed
Singhal 2015 {published data only}
    1. Singhal R, Pandit S, Dhawan N. Deflazacort versus prednisolone: randomized controlled trial in treatment of children with idiopathic nephrotic syndrome. Iranian Journal of Pediatrics 2015;25(2):e510. [MEDLINE: ] - PMC - PubMed
Sinha 2015 {published and unpublished data}
    1. Bagga A, Sinha A, Saha A, Kumar M, Afzal K, Mehta A. Randomized double blind, placebo controlled trial to compare the efficacy of 3-months versus 6-months therapy with prednisolone for the first episode of idiopathic nephrotic syndrome (CTRI/2010/091/001095) [abstract no: P139]. Pediatric Nephrology 2012;27(9):1707. [EMBASE: 71386357]
    1. Sinha A, Bagga A, Sharma S, Saha A, Kumar M, Afzal K, et al. Randomized, double blind, placebo controlled trial to compare the efficacy of 3-months versus 6-months therapy with prednisolone for the first episode of idiopathic nephritic syndrome [abstract no: O-40]. Pediatric Nephrology 2013;28(8):1361-2. [EMBASE: 71126981]
    1. Sinha A, Saha A, Kumar M, Sharma S, Afzal K, Mehta A, et al. Extending initial prednisolone treatment in a randomized control trial from 3 to 6 months did not significantly influence the course of illness in children with steroid- sensitive nephrotic syndrome. Kidney International 2015;87(1):217-24. [MEDLINE: ] - PubMed
Teeninga 2013 {published data only}27871415
    1. Teeninga N, Guan Z, Stevens J, Kist-Van Holthe JE, Ackermans MT, Heijden AJ, et al. Population pharmacokinetics of prednisolone in relation to clinical outcome in children with nephrotic syndrome. Therapeutic Drug Monitoring 2016;38(4):534-45. [EMBASE: 610346284] - PubMed
    1. Teeninga N, Kist-Van Holthe JE, De Mos NI, Peters N, Hop WC, Heijden AJ, et al. Optimal treatment of steroid sensitive nephrotic syndrome in children: a multicenter randomised controlled trial [abstract no: 450]. Pediatric Nephrology 2010;25(9):1884. [EMBASE: 70438552]
    1. Teeninga N, Kist-Van Holthe JE, De Mos NI, Van Rijswijk-Peeters N, Hop WC, Nauta J. Optimal treatment of steroid sensitive nephrotic syndrome in children: a randomised controlled trial [abstract no: P090]. Pediatric Nephrology 2008;23(9):1619. [CENTRAL: CN-01657514]
    1. Teeninga N, Kist-van Holthe JE, den Akker EL, Kersten MC, Boersma E, Krabbe HG, et al. Genetic and in vivo determinants of glucocorticoid sensitivity in relation to clinical outcome of childhood nephrotic syndrome. Kidney International 2014;85(6):1444-53. [MEDLINE: ] - PubMed
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Ueda 1988 {published data only}
    1. Ueda N, Chihara M, Kawaguchi S, Niimomi Y, Nonada T, Matsumoto J, et al. Intermittent versus long-term tapering prednisolone for initial therapy in children with idiopathic nephrotic syndrome. Journal of Pediatrics 1988;112(1):122-6. [MEDLINE: ] - PubMed
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Yadav 2019 {published data only}
    1. Yadav M, Sinha A, Hari P, Bagga A. Efficacy of low-dose daily versus alternate day prednisone in children with frequently relapsing nephrotic syndrome (FRNS): open-label randomized controlled trial (RCT) [abstract no: FP-S25-09]. Pediatric Nephrology 2016;31(10):1752. [EMBASE: 612479637] - PubMed
    1. Yadav M, Sinha A, Khandelwal P, Hari P, Bagga A. Efficacy of low-dose daily versus alternate-day prednisolone in frequently relapsing nephrotic syndrome: an open-label randomized controlled trial. Pediatric Nephrology 2019;34(5):829-35. [MEDLINE: ] - PubMed
Yoshikawa 1998 {published data only}
    1. Ito H, Yoshikawa N. Multicenter controlled trial in nephrotic syndrome in Japanese children [abstract no: S-13.5]. In: 9th Congress. International Pediatric Nephrology Association; 1992 Aug 30 - Sep 4; Jerusalem, Israel. 1992:C37.
    1. Nakanishi K, Iijima K, Ishikura K, Hataya H, Nakazato H, Sasaki S, et al. Two-year outcome of the ISKDC regimen and frequent-relapsing risk in children with idiopathic nephrotic syndrome. Clinical Journal of the American Society of Nephrology: CJASN 2013;8(5):756-62. [MEDLINE: ] - PMC - PubMed
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    1. Yoshikawa N, Ito H, Takehoshi Y, Honda M, Awazu M, Iijima K, et al. Standard versus long-term prednisolone with sairei-to for initial therapy in childhood steroid-responsive nephrotic syndrome: a prospective controlled study. Nippon Jinzon Gakkai Shi [Japanese Journal of Nephrology] 1998;40(8):587-90. [MEDLINE: ] - PubMed
Yoshikawa 2015 {published and unpublished data}
    1. Yoshikawa N, Nakanishi K, Oba MS, Sako M, Ohashi Y, Iijima K. Increased duration and dose of prednisolone (PSL) treatment does not reduce relapses in childhood nephrotic syndrome [abstract no: SA-PO1080]. Journal of the American Society of Nephrology 2014;24(Abstracts):3B.
    1. Yoshikawa N, Nakanishi K, Sako M, Oba MS, Mori R, Ota E, et al. A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment. Kidney International 2015;87(1):225-32. [MEDLINE: ] - PMC - PubMed
Zhang 2007d {published data only}
    1. Zhang Y, Huang JP, Xiao HJ, Ding J, Yao Y, Yang JY. Prospective clinical randomized controlled trial of pulse methylprednisolone therapy in children with steroid sensitive nephrotic syndrome [abstract no: 797 (P)]. Pediatric Nephrology 2007;22(9):1609. [CENTRAL: CN-01912552]

References to studies excluded from this review

APN 2006 {published data only}
    1. Arbeitsgemeinschaft fur Padiatrische Nephrologie. Results of the nephrotic syndrome study VIII of the APN: new standard treatment versus new standard treatment plus 8 weeks cyclosporin A [abstract]. Pediatric Nephrology 1999;13:C26. [CENTRAL: CN-00636143] [CRSEF: 329770]
    1. Hoyer PF, Brodehl J. Initial treatment of idiopathic nephrotic syndrome in children: prednisone versus prednisone plus cyclosporine A: a prospective, randomized trial. Journal of the American Society of Nephrology 2006;17(4):1151–7. [MEDLINE: ] [CRSREF: 3229771] - PubMed
    1. Hoyer PF, Arbeitsgemeinschaft fur Padiatrische Nephrologie. The initial treatment of idiopathic nephrotic syndrome with prednisone and cyclosporin A: preliminary results of a therapeutic trial [abstract no: P147]. Pediatric Nephrology 1995;9(6):C91. [CENTRAL: CN-00401335] [CRSREF: 3229770]
    1. Hoyer PF. Results of the Nephrotic Syndrome Study VIII of the APN: new standard treatment versus new standard treatment plus 8 weeks cyclosporin A [abstract]. Journal of the American Society of Nephrology 1999;10(Program & Abstracts):104A. [CENTRAL: CN-0055522] [CRSREF:3229772]
Zhang 2014 {published data only}
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References to ongoing studies

CTRI/2015/11/006345 {published data only}
    1. Hari P. Efficacy of short prednisolone treatment for relapse in children with steroid sensitive nephrotic syndrome: a randomised controlled study. www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=12315 (first received 5 November 2015).
CTRI/2018/05/013634 {published data only}
    1. Kalra S. A randomized controlled clinical trial to compare the efficacy of standard dose of steroids vs reduced dose in treating relapses in children with steroid sensitive nephrotic syndrome. www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=25815 (first received 3 May 2018).
CTRI/2018/05/014075 {published data only}
    1. Mishra K. A comparison of two doses of prednisolone for relapses in children with steroid sensitive nephrotic syndrome: a randomized controlled non inferiority trial. www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=26036 (first received 23 May 2018).
PREDNOS 2 2014 {published data only}10900733
    1. Webb NJ, Frew E, Brettell EA, Milford DV, Bockenhauer D, Saleem MA, et al. Short course daily prednisolone therapy during an upper respiratory tract infection in children with relapsing steroid-sensitive nephrotic syndrome (PREDNOS 2): protocol for a randomised controlled trial. Trials [Electronic Resource] 2014;15:147. [MEDLINE: ] - PMC - PubMed
RESTERN 2017 {published data only}
    1. Schijvens A, Schreuder M. Steroid treatment reduction in relapsing childhood nephrotic syndrome: a new nationwide randomized controlled trial in the Netherlands - the RESTERN study [abstract no: P-163]. Pediatric Nephrology 2017;32(9):1729. [EMBASE: 618120212]
    1. Schijvens AM, Dorresteijn EM, Roeleveld N, Ter Heine R, Wijk JA, Bouts AH, et al. REducing STEroids in Relapsing Nephrotic syndrome: the RESTERN study- protocol of a national, double-blind, randomised, placebo-controlled, non-inferiority intervention study. BMJ Open 2017;7(9):e018148. [MEDLINE: ] - PMC - PubMed
Sinha 2016 {published data only}
    1. Sinha A, Gipson D, Wong C, Massengil S, Ahmad A, Hari P, et al. 6-months versus 3-months prednisolone for initial therapy of steroid sensitive nephrotic syndrome: open label RCT [abstract no: IPN11430-80]. Pediatric Nephrology 2019;34(10):2076.
    1. Sinha A, Hari P, Bagga A. Randomized controlled trial to compare efficacy of 3-months versus 6-months therapy with prednisolone for the first episode of idiopathic nephrotic syndrome in children <4-yr-old [abstract no: PO-321]. Pediatric Nephrology 2016;31(10):1867-8. [EMBASE: 612479470]

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References to other published versions of this review

Hahn 2015
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