Corticosteroid therapy for nephrotic syndrome in children

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

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.

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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
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. Analysis
10.1. Analysis
Comparison 10 Daily prednisolone treatment during viral infections, Outcome 1 Number with relapse with infection.
10.2. Analysis
10.2. Analysis
Comparison 10 Daily prednisolone treatment during viral infections, Outcome 2 Number of relapses/patient.
10.3. Analysis
10.3. Analysis
Comparison 10 Daily prednisolone treatment during viral infections, Outcome 3 Number of relapses/patient at 2 years.
11.1. Analysis
11.1. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 1 Number of children relapsing during therapy.
11.2. Analysis
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. Analysis
11.3. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 3 Mean relapse rate/patient/y.
11.4. Analysis
11.4. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 4 Mean time to relapse.
11.5. Analysis
11.5. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 5 Cumulative steroid dose.
11.6. Analysis
11.6. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 6 Mean time to remission.
11.7. Analysis
11.7. Analysis
Comparison 11 Steroid therapy in relapse of nephrotic syndrome, Outcome 7 Serious adverse events.
12.1. Analysis
12.1. Analysis
Comparison 12 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 1 Number with relapses.
12.2. Analysis
12.2. Analysis
Comparison 12 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 2 Relapse rate/patient/y.
12.3. Analysis
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. Analysis
12.4. Analysis
Comparison 12 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 4 Cumulative steroid dose.
12.5. Analysis
12.5. Analysis
Comparison 12 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 5 Adverse effects.

Source: PubMed

3
Subskrybuj