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Review
. 2015 Aug 7;2015(8):CD005128.
doi: 10.1002/14651858.CD005128.pub3.

Interventions for preventing and treating kidney disease in Henoch-Schönlein Purpura (HSP)

Deirdre Hahn  1 , Elisabeth M Hodson, Narelle S Willis, Jonathan C Craig
Affiliations
Review

Interventions for preventing and treating kidney disease in Henoch-Schönlein Purpura (HSP)

Deirdre Hahn et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood but may occur in adults. This small vessel vasculitis is characterised by palpable purpura, abdominal pain, arthritis or arthralgia and kidney involvement. This is an update of a review first published in 2009.

Objectives: To evaluate the benefits and harms of different agents (used singularly or in combination) compared with placebo, no treatment or any other agent for: (1) the prevention of severe kidney disease in patients with HSP without kidney disease at presentation; (2) the prevention of severe kidney disease in patients with HSP and minor kidney disease (microscopic haematuria, mild proteinuria) at presentation; (3) the treatment of established severe kidney disease (macroscopic haematuria, proteinuria, nephritic syndrome, nephrotic syndrome with or without acute kidney failure) in HSP; and (4) the prevention of recurrent episodes of HSP-associated kidney disease.

Search methods: We searched the Cochrane Kidney and Transplant's Specialised Register to 13 July 2015 through contact with the Trials Search Co-ordinator using search terms relevant to this review.

Selection criteria: Randomised controlled trials (RCTs) comparing interventions used to prevent or treat kidney disease in HSP compared with placebo, no treatment or other agents were included.

Data collection and analysis: Two authors independently determined study eligibility, assessed risk of bias and extracted data from each study. Statistical analyses were performed using the random effects model and the results were expressed as risk ratio (RR) or risk difference (RD) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI).

Main results: Thirteen studies (1403 enrolled patients) were identified. Risks of bias attributes were frequently poorly performed. Low risk of bias was reported in six studies (50%) for sequence generation (selection bias) and in seven (58%) for allocation concealment (selection bias). Blinding of participants and personnel (performance bias) and of outcome assessment (detection bias) was at low risk of bias in three studies. Five studies reported complete outcome data (attrition bias) while eight studies reported expected outcomes so were at low risk of reporting bias.Eight studies evaluated therapy to prevent persistent kidney disease in HSP. There was no significant difference in the risk of persistent kidney disease any time after treatment (5 studies, 746 children: RR 0.74, 95% CI 0.42 to 1.32), or at one, three, six and 12 months in children given prednisone for 14 to 28 days at presentation of HSP compared with placebo or supportive treatment. There were no significant differences in the risk of persistent kidney disease with antiplatelet therapy in children with or without kidney disease at entry. Heparin significantly reduced the risk of persistent kidney disease by three months compared with placebo (1 study, 228 children: RR 0.27, 95% CI 0.14 to 0.55); no significant bleeding occurred. Four studies examined the treatment of severe HSP-associated kidney disease. Two studies (one involving 56 children and the other involving 54 adults) compared cyclophosphamide with placebo or supportive treatment and found no significant benefit of cyclophosphamide. There were no significant differences in adverse effects. In one study comparing cyclosporin with methylprednisolone (15 children) there was no significant difference in remission at final follow-up at a mean of 6.3 years (RR 1.37, 95% CI 0.74 to 2.54). In one study (17 children) comparing mycophenolate mofetil with azathioprine, there was no significant difference in the remission of proteinuria at one year (RR 1.32, 95% CI 0.86 to 2.03). No studies were identified which evaluated the efficacy of therapy on kidney disease in participants with recurrent episodes of HSP.

Authors' conclusions: There are no substantial changes in conclusions from this update compared with the initial review. From generally low quality evidence, we found no evidence of benefit from RCTs for the use of prednisone or antiplatelet agents to prevent persistent kidney disease in children with HSP. Though heparin appeared effective, this potentially dangerous therapy is not justified to prevent serious kidney disease when fewer than 2% of children with HSP develop severe kidney disease. No evidence of benefit has been found for cyclophosphamide treatment in children or adults with HSP and severe kidney disease. Because of small patient numbers and events leading to imprecision in results, it remains unclear whether cyclosporin and mycophenolate mofetil have any roles in the treatment of children with HSP and severe kidney disease.

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Conflict of interest statement

  1. Deirdre Hahn: nothing to declare

  2. Elisabeth Hodson: nothing to declare

  3. Narelle Willis: nothing to declare

  4. Jonathan Craig: nothing to declare

Figures

1
1
Flow diagram of included and excluded study in Review
2
2
Risk of bias: Review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Risk of bias: Review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1 Prednisone versus placebo/supportive treatment for preventing persistent kidney disease, Outcome 1 Persistent kidney disease at any time after treatment.
1.2
1.2. Analysis
Comparison 1 Prednisone versus placebo/supportive treatment for preventing persistent kidney disease, Outcome 2 Number of children with any continuing kidney disease at different time points.
1.3
1.3. Analysis
Comparison 1 Prednisone versus placebo/supportive treatment for preventing persistent kidney disease, Outcome 3 Any continuing kidney disease at different time points (study with high risk of bias excluded).
1.4
1.4. Analysis
Comparison 1 Prednisone versus placebo/supportive treatment for preventing persistent kidney disease, Outcome 4 Number of children with kidney disease in first month/with kidney disease at follow‐up.
1.5
1.5. Analysis
Comparison 1 Prednisone versus placebo/supportive treatment for preventing persistent kidney disease, Outcome 5 Number developing severe kidney disease.
1.6
1.6. Analysis
Comparison 1 Prednisone versus placebo/supportive treatment for preventing persistent kidney disease, Outcome 6 Duration of kidney disease.
1.7
1.7. Analysis
Comparison 1 Prednisone versus placebo/supportive treatment for preventing persistent kidney disease, Outcome 7 Gastrointestinal complications requiring hospital admission.
1.8
1.8. Analysis
Comparison 1 Prednisone versus placebo/supportive treatment for preventing persistent kidney disease, Outcome 8 Eight‐year outcomes.
2.1
2.1. Analysis
Comparison 2 Antiplatelet agents versus supportive treatment for preventing persistent kidney disease, Outcome 1 Kidney disease at any time.
2.2
2.2. Analysis
Comparison 2 Antiplatelet agents versus supportive treatment for preventing persistent kidney disease, Outcome 2 Kidney disease at any time.
3.1
3.1. Analysis
Comparison 3 Heparin versus placebo for preventing persistent kidney disease, Outcome 1 Any kidney disease at 3 months after onset or relapse.
3.2
3.2. Analysis
Comparison 3 Heparin versus placebo for preventing persistent kidney disease, Outcome 2 Type of kidney disease at 3 months or more after onset or relapse.
3.3
3.3. Analysis
Comparison 3 Heparin versus placebo for preventing persistent kidney disease, Outcome 3 Time to development of kidney disease.
4.1
4.1. Analysis
Comparison 4 Cyclophosphamide versus supportive treatment for treating severe kidney disease, Outcome 1 Persistent kidney disease.
4.2
4.2. Analysis
Comparison 4 Cyclophosphamide versus supportive treatment for treating severe kidney disease, Outcome 2 Persistent severe kidney disease.
4.3
4.3. Analysis
Comparison 4 Cyclophosphamide versus supportive treatment for treating severe kidney disease, Outcome 3 ESKD.
5.1
5.1. Analysis
Comparison 5 Cyclophosphamide + steroids versus steroids, Outcome 1 Primary outcome: BVAS at 6 months.
5.2
5.2. Analysis
Comparison 5 Cyclophosphamide + steroids versus steroids, Outcome 2 Secondary endpoints at 12 months.
5.3
5.3. Analysis
Comparison 5 Cyclophosphamide + steroids versus steroids, Outcome 3 Adverse effects.
6.1
6.1. Analysis
Comparison 6 Cyclosporin versus methylprednisolone for treating severe kidney disease, Outcome 1 Number with remission at 3 months.
6.2
6.2. Analysis
Comparison 6 Cyclosporin versus methylprednisolone for treating severe kidney disease, Outcome 2 Number with remission at last follow‐up (mean 6.3 years).
7.1
7.1. Analysis
Comparison 7 Mycophenolate mofetil versus azathioprine for treating severe kidney disease, Outcome 1 Remission of proteinuria at 1 year.
7.2
7.2. Analysis
Comparison 7 Mycophenolate mofetil versus azathioprine for treating severe kidney disease, Outcome 2 Regression of histological lesions at 1 year.
8.1
8.1. Analysis
Comparison 8 Fosinopril + supportive treatment versus supportive treatment, Outcome 1 Proteinuria.
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References

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References to other published versions of this review

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