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Meta-Analysis
. 2015 Mar 18;2015(3):CD001533.
doi: 10.1002/14651858.CD001533.pub5.

Corticosteroid therapy for nephrotic syndrome in children

Deirdre Hahn  1 , Elisabeth M Hodson, Narelle S Willis, Jonathan C Craig
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 the blood to 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 mortality 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 2003, 2005 and 2007.

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 Renal Group's Specialised Register to 26 February 2015 through contact with the Trials Search Co-ordinator using search terms relevant to this review.

Selection criteria: Randomised controlled trials (RCTs) performed in children (three months 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: Ten new studies were identified so a total of 34 studies (3033 total participants) were included in the 2015 review update. The risk of bias attributes were frequently poorly performed. Low risk of bias was reported in 18 studies for sequence generation, 16 studies for allocation concealment, seven for performance and detection bias, 15 for incomplete reporting and 16 for selective reporting. Three months or more of prednisone significantly reduced the risk of frequently relapsing nephrotic syndrome (FRNS) (6 studies, 582 children: RR 0.68, 95% CI 0.47 to 1.00) and of relapse by 12 to 24 months (8 studies, 741 children: RR 0.80, 95% CI 0.64 to 1.00) compared with two months. Five or six months of prednisone significantly reduced the risk of relapse (7 studies, 763 children: RR 0.62, 95% CI 0.45 to 0.85) but not FRNS (5 studies, 591 children: RR 0.78, 95% CI 0.50 to 1.22) compared with three months. However there was significant heterogeneity in the analyses. Subgroup analysis stratified by risk of bias for allocation concealment showed that the risk for FRNS did not differ significantly between two or three months of prednisone and three to six months among studies at low risk of bias but was significantly reduced in extended duration studies compared with two or three months in studies at high risk or unclear risk of bias. There were no significant differences in the risk of adverse effects between extended duration and two or three months of prednisone. Four studies found that in children with FRNS, daily prednisone during viral infections compared with alternate-day prednisone or no treatment significantly reduced the rate of relapse.

Authors' conclusions: In this 2015 update the addition of three well-designed studies has changed the conclusion of this review. Studies of long versus shorter duration of corticosteroids have heterogeneous treatment effects, with the older high risk of bias studies tending to over-estimate the effect of longer course therapy, compared with more recently published low risk of bias studies. Among studies at low risk of bias, there was no significant difference in the risk for FRNS between prednisone given for two or three months and longer durations or total dose of therapy indicating that there is no benefit of increasing the duration of prednisone beyond two or three months in the initial episode of SSNS.The risk of relapse in children with FRNS is reduced by the administration of daily prednisone at onset of an upper respiratory tract or viral infection. Three additional studies have increased the evidence supporting this conclusion. This management strategy may be considered for children with FRNS. A paucity of data on prednisone use in relapsing nephrotic syndrome remains. In particular there are no data from RCTs evaluating the efficacy and safety of prolonged courses of low dose alternate-day prednisone although this management strategy is recommended in current guidelines.

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Conflict of interest statement

  1. Deirdre Hahn: none known

  2. Elisabeth Hodson: none known

  3. Narelle Willis: none known

  4. Jonathan Craig: 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.
1.1
1.1. Analysis
Comparison 1 Steroid therapy in first episode of nephrotic syndrome: 3 months versus 2 months of therapy, Outcome 1 Number with frequent relapses by 12 to 24 months.
1.2
1.2. Analysis
Comparison 1 Steroid therapy in first episode of nephrotic syndrome: 3 months versus 2 months of therapy, Outcome 2 Number of children relapsing by 12 to 24 months.
1.3
1.3. Analysis
Comparison 1 Steroid therapy in first episode of nephrotic syndrome: 3 months versus 2 months of therapy, Outcome 3 Mean relapse rate/patient/y.
1.4
1.4. Analysis
Comparison 1 Steroid therapy in first episode of nephrotic syndrome: 3 months versus 2 months of therapy, Outcome 4 Cumulative steroid dose.
1.5
1.5. Analysis
Comparison 1 Steroid therapy in first episode of nephrotic syndrome: 3 months versus 2 months of therapy, Outcome 5 Number with frequent relapses by 12 to 24 months stratified by definition of FRNS.
1.6
1.6. Analysis
Comparison 1 Steroid therapy in first episode of nephrotic syndrome: 3 months versus 2 months of therapy, Outcome 6 Number with frequent relapses by 12 to 24 months stratified by risk of bias for allocation concealment.
1.7
1.7. Analysis
Comparison 1 Steroid therapy in first episode of nephrotic syndrome: 3 months versus 2 months of therapy, Outcome 7 Adverse events.
2.1
2.1. Analysis
Comparison 2 Steroid therapy in first episode of nephrotic syndrome: 5 or 6 months versus 3 months of therapy, Outcome 1 Number with frequent relapses by 12 to 24 months.
2.2
2.2. Analysis
Comparison 2 Steroid therapy in first episode of nephrotic syndrome: 5 or 6 months versus 3 months of therapy, Outcome 2 Number of children relapsing by 12 to 24 months.
2.3
2.3. Analysis
Comparison 2 Steroid therapy in first episode of nephrotic syndrome: 5 or 6 months versus 3 months of therapy, Outcome 3 Mean relapse rate/patient/y.
2.4
2.4. Analysis
Comparison 2 Steroid therapy in first episode of nephrotic syndrome: 5 or 6 months versus 3 months of therapy, Outcome 4 Cumulative steroid dose.
2.5
2.5. Analysis
Comparison 2 Steroid therapy in first episode of nephrotic syndrome: 5 or 6 months versus 3 months of therapy, Outcome 5 Number with frequent relapses stratified by definition of FRNS.
2.6
2.6. Analysis
Comparison 2 Steroid therapy in first episode of nephrotic syndrome: 5 or 6 months versus 3 months of therapy, Outcome 6 Number with frequent relapses stratified by risk of bias for allocation concealment.
2.7
2.7. Analysis
Comparison 2 Steroid therapy in first episode of nephrotic syndrome: 5 or 6 months versus 3 months of therapy, Outcome 7 Number with frequent relapses stratified by risk of bias for blinding.
2.8
2.8. Analysis
Comparison 2 Steroid therapy in first episode of nephrotic syndrome: 5 or 6 months versus 3 months of therapy, Outcome 8 Number with frequent relapses stratified by risk of bias for attrition.
2.9
2.9. Analysis
Comparison 2 Steroid therapy in first episode of nephrotic syndrome: 5 or 6 months versus 3 months of therapy, Outcome 9 Adverse events.
3.1
3.1. Analysis
Comparison 3 Steroid therapy in the first episode of nephrotic syndrome: 1 month versus 2 months of therapy, Outcome 1 Number of children relapsing by 6 months.
3.2
3.2. Analysis
Comparison 3 Steroid therapy in the first episode of nephrotic syndrome: 1 month versus 2 months of 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 of nephrotic syndrome: 1 month versus 2 months of therapy, Outcome 3 Number with frequent relapses.
3.4
3.4. Analysis
Comparison 3 Steroid therapy in the first episode of nephrotic syndrome: 1 month versus 2 months of therapy, Outcome 4 Cumulative steroid dose.
4.1
4.1. Analysis
Comparison 4 Steroid therapy in the first episode of nephrotic syndrome: 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 same duration, Outcome 1 Relapse at twelve months.
5.2
5.2. Analysis
Comparison 5 Steroid therapy in the first episode of nephrotic syndrome: different total doses given over same duration, Outcome 2 Number with frequently relapsing nephrotic syndrome.
5.3
5.3. Analysis
Comparison 5 Steroid therapy in the first episode of nephrotic syndrome: different total doses given over same duration, Outcome 3 Adverse effects.
6.1
6.1. Analysis
Comparison 6 Steroid therapy and Sairei‐to in first episode of nephrotic syndrome, Outcome 1 Long prednisone & Sairei‐to versus standard prednisone & Sairei‐to.
7.1
7.1. Analysis
Comparison 7 Cyclosporin (CSA) and steroid therapy in first episode of childhood nephrotic syndrome, Outcome 1 Relapse by 6 months.
7.2
7.2. Analysis
Comparison 7 Cyclosporin (CSA) and steroid therapy in first episode of childhood nephrotic syndrome, Outcome 2 Relapse by 12 months.
7.3
7.3. Analysis
Comparison 7 Cyclosporin (CSA) and steroid therapy in first episode of childhood nephrotic syndrome, Outcome 3 Number needing cytotoxic agents.
7.4
7.4. Analysis
Comparison 7 Cyclosporin (CSA) and steroid therapy in first episode of childhood nephrotic syndrome, Outcome 4 Serum creatinine at end of study.
8.1
8.1. Analysis
Comparison 8 Steroid therapy in first episode of nephrotic syndrome: high dose methylprednisone versus 2 month therapy, Outcome 1 Time to first relapse.
8.2
8.2. Analysis
Comparison 8 Steroid therapy in first episode of nephrotic syndrome: high dose methylprednisone versus 2 month therapy, Outcome 2 Relapse rate.
8.3
8.3. Analysis
Comparison 8 Steroid therapy in first episode of nephrotic syndrome: high dose methylprednisone versus 2 month therapy, Outcome 3 Time to remission.
9.1
9.1. Analysis
Comparison 9 Steroid therapy and azithromycin (AZM) in the first episode of nephrotic syndrome, Outcome 1 Number of children relapsing by 6 months.
10.1
10.1. Analysis
Comparison 10 Daily prednisolone treatment during viral infections, Outcome 1 Number with relapse with infection.
10.2
10.2. Analysis
Comparison 10 Daily prednisolone treatment during viral infections, Outcome 2 Number of relapses/patient.
10.3
10.3. Analysis
Comparison 10 Daily prednisolone treatment during viral infections, Outcome 3 Number of relapses/patient at 2 years.
11.1
11.1. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 1 Number of children relapsing during therapy.
11.2
11.2. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 2 Number of children with further relapses by 9 to 12 months.
11.3
11.3. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 3 Mean relapse rate/patient/y.
11.4
11.4. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 4 Mean time to relapse.
11.5
11.5. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 5 Cumulative steroid dose.
11.6
11.6. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 6 Mean time to remission.
11.7
11.7. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 7 Serious adverse events.
12.1
12.1. Analysis
Comparison 12 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 1 Number with relapses.
12.2
12.2. Analysis
Comparison 12 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 2 Relapse rate/patient/y.
12.3
12.3. Analysis
Comparison 12 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 3 Number with frequently relapsing or steroid dependent nephrotic syndrome.
12.4
12.4. Analysis
Comparison 12 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 4 Cumulative steroid dose.
12.5
12.5. Analysis
Comparison 12 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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Broyer 1997 {published data only}
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Ekka 1997 {published data only}
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Gulati 2009 {published data only}
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Hiraoka 2000 {published data only}
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ISKDC 1979 {published data only}
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Jayantha 2002a {published and unpublished data}
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Jayantha 2002b {published and unpublished data}
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Kleinknecht 1982 {published and unpublished data}
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Ksiazek 1995 {published data only}
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Leisti 1978 {published data only}
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Li 1994 {published data only}
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Liern 2008 {published data only}
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Mattoo 2000 {published data only}
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Mishra 2012 {published data only}
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Mocan 1999 {published data only}
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Norero 1996 {published data only}
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Pecoraro 2003 {published data only}
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Satomura 2001 {published data only}
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Sharma 2000 {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]
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Sinha 2014 {published and unpublished data}
    1. Bagga A, Sinha A, Saha A, Kumar M, Afzal K, Mehta A, 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 nephrotic syndrome (CTRI/2010/091/001095) [abstract]. Pediatric Nephrology 2012;27(9):1707. [EMBASE: 71386357]
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    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 2014;87(1):217‐24. [MEDLINE: ] - PubMed
Teeninga 2013 {published data only}
    1. Teeninga N, Kist‐Van Holthe JE, Ruswuk N, Mos NI, Hop WC, Wetzels JF, et al. Effect of extended prednisolone treatment from three to six months, with equal cumulative doses, on childhood nephrotic syndrome: a nation‐wide randomised controlled trial [abstract]. Pediatric Nephrology 2012;27(9):1637‐8. [EMBASE: 71386208]
    1. Teeninga N, Kist‐van Holthe JE, Rijswijk N, Mos NI, Hop WC, Wetzels JF, et al. Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome. Journal of the American Society of Nephrology 2013;24(1):149‐59. [MEDLINE: ] - PMC - PubMed
    1. Teeninga N, Kist‐van Holthe JE, 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
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
Yoshikawa 1998 {published data only}
    1. Takekoshi Y. Treatment of idiopathic nephrotic syndrome [abstract]. Pediatric Nephrology 1996;10(1):C3. [CENTRAL: CN‐00402800]
    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 2014 {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 2014;87(1):225‐32. [MEDLINE: ] - PMC - PubMed
Zhang 2014 {published data only}
    1. Zhang B, Liu T, Wang W, Zhang X, Fan S, Liu Z, et al. A prospective randomly controlled clinical trial on azithromycin therapy for induction treatment of children with nephrotic syndrome. European Journal of Pediatrics 2014;173(4):509‐15. [MEDLINE: ] - PubMed

References to studies excluded from this review

Alatas 1978 {published data only}
    1. Alatas H, Wirya IG, Tambunan T, Himawan S. Controlled trial of chlorambucil in frequently relapsing nephrotic syndrome in children (a preliminary report). Journal of the Medical Association of Thailand 1978;61 Suppl 1:222‐8. [MEDLINE: ] - PubMed
Anonymous 1968 {published data only}
    1. Anonymous. Nephrotic syndrome in children [Die nefrotiese sindroom by kinders]. South African Medical Journal. Suid‐Afrikaanse Tydskrif Vir Geneeskunde 1968;42(2):21‐2. [MEDLINE: ] - PubMed
APN 1982 {published data only}
    1. Anonymous. Effect of cytotoxic drugs in frequently relapsing nephrotic syndrome with and without steroid dependence. New England Journal of Medicine 1982;306(8):451‐4. [MEDLINE: ] - PubMed
    1. Brodehl J, Krohn HP, Ehrich JH. The treatment of minimal change nephrotic syndrome (lipoid nephrosis): cooperative studies of the Arbeitsgemeinschaft fur Padiatrische Nephrologie (APN). Klinische Padiatrie 1982;194(3):162‐5. [MEDLINE: ] - PubMed
Arun 2009 {published data only}
    1. Arun S, Bagga A, Bhatnagar S, Hari P, Menon S, Saini S. Efficacy of Zinc(Zn) in reducing relapses in steroid sensitive nephrotic syndrome (SSNS) double blind, randomized controlled trial (RCT) (CRG030600044) [abstract no: 184OP]. Pediatric Nephrology 2007;22(9):1481. [CENTRAL: CN‐00724915] - PubMed
    1. Arun S, Bhatnagar S, Menon S, Saini S, Hari P, Bagga A. Efficacy of zinc supplements in reducing relapses in steroid‐sensitive nephrotic syndrome. Pediatric Nephrology 2009;24(8):1583‐6. [MEDLINE: ] - PubMed
Baluarte 1978 {published data only}
    1. Baluarte HJ, Hiner L, Gruskin AB. Chlorambucil dosage in frequently relapsing nephrotic syndrome: a controlled clinical trial. Journal of Pediatrics 1978;92(2):295‐8. [MEDLINE: ] - PubMed
BAPN 1991 {published data only}
    1. Anonymous. Levamisole for corticosteroid‐dependent nephrotic syndrome in childhood. British Association for Paediatric Nephrology. Lancet 1991;337(8757):1555‐7. [MEDLINE: ] - PubMed
Barratt 1970 {published data only}
    1. Barratt TM, Soothill JF. A controlled trial of cyclophosphamide in steroid sensitive relapsing nephrotic syndrome of childhood [abstract]. Nephron 1971;8:95. [CENTRAL: CN‐00253521] - PubMed
    1. Barratt TM, Soothill JF. Controlled trial of cyclophosphamide in steroid‐sensitive relapsing nephrotic syndrome of childhood. Lancet 1970;2(7671):479‐2. [MEDLINE: ] - PubMed
Barratt 1973 {published data only}
    1. Barratt TM, Cameron JS, Chantler C, Ogg CS, Soothill JF. Comparative trial of 2 weeks and 8 weeks cyclophosphamide in steroid‐sensitive relapsing nephrotic syndrome of childhood. Archives of Disease in Childhood 1973;48(4):286‐90. [MEDLINE: ] - PMC - PubMed
Barratt 1977 {published data only}
    1. Barratt TM, Cameron JS, Chantler C, Counahan R, Ogg CS, Soothill JF. Controlled trial of azathioprine in treatment of steroid‐responsive nephrotic syndrome of childhood. Archives of Disease in Childhood 1977;52(6):462‐3. [MEDLINE: ] - PMC - PubMed
Cerkauskiene 2005 {published data only}
    1. Cerkauskiene R, Kaltenis P. Comparative study of prednisolone alone and prednisolone plus fusidic acid in the treatment of children with steroid‐responsive nephrotic syndrome. Medicina (Kaunas, Lithuania) 2005;41 Suppl 1:26‐30. [MEDLINE: ] - PubMed
Chiu 1973 {published data only}
    1. Chiu J, McLaine PN, Drummond KN. A controlled prospective study of cyclophosphamide in relapsing, corticosteroid‐responsive, minimal‐lesion nephrotic syndrome in childhood. Journal of Pediatrics 1973;82(4):607‐13. [MEDLINE: ] - PubMed
Dayal 1994 {published data only}
    1. Dayal U, Dayal AK, Shastry JC, Raghupathy P. Use of levamisole in maintaining remission in steroid‐sensitive nephrotic syndrome in children [erratum appears in Nephron 1994;67(4):507]. Nephron 1994;66(4):408‐12. [MEDLINE: ] - PubMed
Donia 2005 {published data only}
    1. Donia A, Ammar H, Moustafa F, Sobh M. Long‐term efficacy of two unconventional adjunctive therapies in minimal change nephrotic children [abstract]. 41st Congress. European Renal Association. European Dialysis and Transplantation Association; 2004 May 15‐18; Lisbon, Portugal. 2004:37. [CENTRAL: CN‐00509161]
    1. Donia AF, Ammar HM, Agroudy A, Moustafa F, Sobh MA. Long‐term results of two unconventional agents in steroid‐dependent nephrotic children. Pediatric Nephrology 2005;20(10):1420‐5. [MEDLINE: ] - PubMed
Edefonti 1988 {published data only}
    1. Edefonti A, Ghio L, Bettinelli A, Paterlini G, Giani M, Nebbia G, et al. Unconjugated hyperbilirubinemia due to ciclosporin administration in children with nephrotic syndrome. Contributions to Nephrology 1988;67:121‐4. [MEDLINE: ] - PubMed
    1. Edefonti A, Ghio L, Bettinelli G, Paterlini M, Giani G Nebbia A, et al. Unconjugated hyperbilirubinemia due to cyclosporin A (CYA) administration in children with nephrotic syndrome [abstract]. Pedatric Nephrology 1987;1(1):C8. [CENTRAL: CN‐00465774] - PubMed
    1. Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R, Lama G, et al. Cyclosporine (CSA) vs cyclophosphamide (CYC) for children with frequently relapsing/steroid dependent nephrotic syndrome (FR/SDNS): long term study [abstract]. Journal of the American Society of Nephrology 1992;3(3):310.
    1. Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R, Lama G, et al. Cyclosporine (CSA) vs cyclophosphamide (CYC) for children with frequently relapsing/steroid dependent nephrotic syndrome: long term study [abstract]. 9th Congress of the International Pediatric Nephrology Association; 1992 Aug 30‐Sep 4; Jerusalem (Israel). 1992:C70. [CENTRAL: CN‐00483820]
    1. Ponticelli C. A multicenter controlled prospective trial with cyclosporine vs cyclophosphamide in frequent relapsers and steroid dependent patients with idiopathic nephrotic syndrome. Journal of Nephrology 1989;2(2):147‐51. [EMBASE: 1991014828]
Grupe 1976 {published data only}
    1. Grupe WE, Makker SP, Ingelfinger JR. Chlorambucil treatment of frequently relapsing nephrotic syndrome. New England Journal of Medicine 1976;295(14):746‐9. [MEDLINE: ] - PubMed
Hu 2006 {published data only}
    1. Hu GH, Dang XQ, Wang JH. Clinical effect of shenbing mistura combined with glucocorticoid on recurrent nephrotic syndrome in children and levels of interleukin‐6 and tumor necrosis factor‐alpha in blood and urine. Zhongguo Zhongxiyi Jiehe Zazhi [Chinese Journal of Integrated Traditional & Western Medicine] 2006;26(10):892‐5. [MEDLINE: ] - PubMed
Idczak‐Nowicka 1996 {published data only}
    1. Idczak‐Nowicka E, Ksiazek J, Krynski J, Wyszynska T. Verification of indications for kidney biopsy in children with steroid‐dependent nephrotic syndrome [Weryfikacja wskazan do biopsji nerki u dzieci ze sterydozaleznym zespolem nerczycowym]. Pediatria Polska 1996;71(8):679‐83. [MEDLINE: ] - PubMed
ISKDC 1970 {published data only}
    1. Abramowicz M, Barnett HL, Edelmann CM Jr, Griefer I, Kobayashi O, Arneil GC, et al. Controlled trial of azathioprine in children with nephrotic syndrome. A report for the international study of kidney disease in children. Lancet 1970;1(7654):959‐61. [MEDLINE: ] - PubMed
    1. Arneil GC. International trial of azathioprine in nephrotic syndrome in childhood. Nephron 1971;8:95. [CENTRAL: CN‐00253520]
ISKDC 1974 {published data only}
    1. Anonymous. Prospective, controlled trial of cyclophosphamide therapy in children with nephrotic syndrome. Report of the International study of Kidney Disease in Children. Lancet 1974;2(7878):423‐7. [MEDLINE: ] - PubMed
Liu 1995 {published data only}
    1. Liu XY. Therapeutic effect of chai‐ling‐tang (sairei‐to) on the steroid‐dependent nephrotic syndrome in children. American Journal of Chinese Medicine 1995;23(3‐4):255‐60. [MEDLINE: ] - PubMed
Martinelli 2004 {published data only}
    1. Martinelli R, Pereira LJ, Silva OM, Okumura AS, Rocha H. Cyclophosphamide in the treatment of focal segmental glomerulosclerosis. Brazilian Journal of Medical & Biological Research 2004;37(9):1365‐72. [MEDLINE: ] - PubMed
McCrory 1973 {published data only}
    1. McCrory WW, Shibuya M, Lu WH, Lewy JE. Therapeutic and toxic effects observed with different dosage programs of cyclophosphamide in treatment of steroid‐responsive but frequently relapsing nephrotic syndrome. Journal of Pediatrics 1973;82(4):614‐8. [MEDLINE: ] - PubMed
Niaudet 1992 {published data only}
    1. Niaudet P. Comparison of cyclosporin and chlorambucil in the treatment of steroid‐dependent idiopathic nephrotic syndrome: A multicentre randomized controlled trial. The French Society of Paediatric Nephrology. Pediatric Nephrology 1992;6(1):1‐3. [MEDLINE: ] - PubMed
Prasad 2004 {published data only}
    1. Prasad N, Gulati S, Sharma RK, Singh U, Ahmed M. Pulse cyclophosphamide therapy in steroid‐dependent nephrotic syndrome. Pediatric Nephrology 2004;19(5):494‐8. [MEDLINE: ] - PubMed
Rashid 1996 {published data only}
    1. Rashid HU, Ahmed S, Fatima N, Khanam A. Levamisole in the treatment of steroid dependent or frequent relapsing nephrotic syndrome in children. Bangladesh Renal Journal 1996;15(1):6‐8. [EMBASE: 1996266847]
Sharipov 2007 {published data only}
    1. Sharipov AM, Khamzaeva KA. Current aspects of transformation of morphological changes in children with nephrotic syndrome depending on the treatment regimen. Urologiia (Moscow, Russia) 2007, (2):68‐71. [MEDLINE: ] - PubMed
Ueda 1990 {published data only}
    1. Ueda N, Kuno K, Ito S. Eight and 12 week courses of cyclophosphamide in nephrotic syndrome. Archives of Disease in Childhood 1990;65(10):1147‐59. [MEDLINE: ] - PMC - PubMed
Wang 2005 {published data only}
    1. Wang YP, Liu AM, Dai YW, Yang C, Tang HF. The treatment of relapsing primary nephrotic syndrome in children. Journal of Zhejiang University Science. B 2005;6(7):682‐5. [MEDLINE: ] - PMC - PubMed
Weiss 1993 {published data only}
    1. Weiss R. Results of a randomized, double‐blind, placebo controlled, multi‐center clinical trial of levamisole for the treatment of children with frequently relapsing or steroid dependent nephrotic syndrome. Personal communication 2005.
    1. Weiss R, NY‐NJ‐Phila‐Pediatric Nephrology Study Group. Randomized, double‐blind, placebo (P) controlled trial of levamisole (L) for children (CH) with frequently relapsing/steroid dependant (FR/SD) nephrotic syndrome (NS) [abstract]. Journal of the American Society of Nephrology 1993;4(Program & Abstracts):289. [CENTRAL: CN‐00520404]
Wingen 1990 {published data only}
    1. Wingen AM, Muller‐Wiefel DE, Scharer K. Comparison of different regimens of prednisone therapy in frequently relapsing nephrotic syndrome. Acta Paediatrica Scandinavica 1990;79(3):305‐10. [MEDLINE: ] - PubMed
Yamashita 1971 {published data only}
    1. Yamashita F, Funatsu T, Nagayama K, Arihiro H, Anan S. Evaluation of alternate‐day steroid therapy for nephrotic syndrome in childhood by cross‐over study. Kurume Medical Journal 1971;18(3):153‐60. [MEDLINE: ] - PubMed
Yang 2001 {published data only}
    1. Yang RY, Xu LF, Wang Q. The effect of Xuezhikang on lipid metabolism in patients with nephrotic syndrome. Hubei Yikedaxue Xuebao 2001;22(1):55‐7.
Yoshioka 2000 {published data only}
    1. Yoshioka K, Ohashi Y, Sakai T, Ito H, Yoshikawa N, Nakamura H, et al. A multicenter trial of mizoribine compared with placebo in children with frequently relapsing nephrotic syndrome. Kidney International 2000;58(1):317‐24. [MEDLINE: ] - PubMed
    1. Yoshioka K, Ohashi Y, Sakai T, Ito H, Yoshikawa N, Nakamura H, et al. Placebo‐controlled trial of mizoribine (MZR) in children with frequently relapsing nephrotic syndrome (FRNS). The Pediatric Mizoribine Study Group [abstract]. Journal of the American Society of Nephrology 1998;9(Program & Abstracts):163A.

References to ongoing studies

PREDNOS 2 Study 2014 {published data only}
    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 2014;15:147. [MEDLINE: ] - PMC - PubMed
PREDNOS Study 2013 {published data only}
    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. www.controlled‐trials.com/ISRCTN16645249 (accessed 26 February 2015).

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References to other published versions of this review

Hodson 2000
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