Corticosteroid therapy for nephrotic syndrome in children

Elisabeth M Hodson; Narelle S Willis; Jonathan C Craig

doi:10.1002/14651858.CD001533.pub4

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Figure 1

Correlation between relative risk for relapse (Y axis) and duration of therapy (X axis) showing that relative risk for relapse decreases with increase in duration of prednisone therapy.

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Figure 2

Correlation between relative risk for relapse (Y axis) and total induction dose of prednisone (X axis) showing that the relative risk for relapse falls with increase in dose of prednisone therapy.

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Figure 3

Reduction in risk of relapse was primarily associated with an increase in duration not dose since an increase in dose/month appeared to be associated with increased rather than decreased RR for relapse.

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Analysis 1.1

Comparison 1 Steroid therapy in first episode of nephrotic syndrome: comparisons with ISKDC standard therapy, Outcome 1 Number of children relapsing by 6 months.

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Analysis 1.2

Comparison 1 Steroid therapy in first episode of nephrotic syndrome: comparisons with ISKDC standard therapy, Outcome 2 Number of children relapsing by 12‐24 months.

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Analysis 1.3

Comparison 1 Steroid therapy in first episode of nephrotic syndrome: comparisons with ISKDC standard therapy, Outcome 3 Mean relapse rate/patient/year.

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Analysis 1.4

Comparison 1 Steroid therapy in first episode of nephrotic syndrome: comparisons with ISKDC standard therapy, Outcome 4 Number with frequent relapses.

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Analysis 1.5

Comparison 1 Steroid therapy in first episode of nephrotic syndrome: comparisons with ISKDC standard therapy, Outcome 5 Cumulative steroid dose in g/m².

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Analysis 1.6

Comparison 1 Steroid therapy in first episode of nephrotic syndrome: comparisons with ISKDC standard therapy, Outcome 6 Adverse events: increased prednisone dose versus standard duration.

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Analysis 1.7

Comparison 1 Steroid therapy in first episode of nephrotic syndrome: comparisons with ISKDC standard therapy, Outcome 7 Subgroup analysis: Relapse at 12‐24 months according to adequacy of allocation concealment.

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Analysis 2.1

Comparison 2 Steroid therapy in first episode of nephrotic syndrome: comparisons of 3 months or more of steroids, Outcome 1 Number of children relapsing by 6 months.

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Analysis 2.2

Comparison 2 Steroid therapy in first episode of nephrotic syndrome: comparisons of 3 months or more of steroids, Outcome 2 Number of children relapsing by 12‐24 months.

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Analysis 2.3

Comparison 2 Steroid therapy in first episode of nephrotic syndrome: comparisons of 3 months or more of steroids, Outcome 3 Mean relapse rate/patient/year.

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Analysis 2.4

Comparison 2 Steroid therapy in first episode of nephrotic syndrome: comparisons of 3 months or more of steroids, Outcome 4 Number with frequent relapses.

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Analysis 2.5

Comparison 2 Steroid therapy in first episode of nephrotic syndrome: comparisons of 3 months or more of steroids, Outcome 5 Cumulative steroid dose in g/m².

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Analysis 2.6

Comparison 2 Steroid therapy in first episode of nephrotic syndrome: comparisons of 3 months or more of steroids, Outcome 6 Adverse events: 6 months versus 3 months duration.

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Analysis 3.1

Comparison 3 Steroid therapy and Sairei‐to in first episode of nephrotic syndrome, Outcome 1 Long prednisone & Sairei‐to versus standard prednisone & Sairei‐to.

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Analysis 4.1

Comparison 4 Cyclosporin and steroid therapy in first episode of childhood nephrotic syndrome, Outcome 1 Relapse by 6 months.

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Analysis 4.2

Comparison 4 Cyclosporin and steroid therapy in first episode of childhood nephrotic syndrome, Outcome 2 Relapse by 12 months.

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Analysis 4.3

Comparison 4 Cyclosporin and steroid therapy in first episode of childhood nephrotic syndrome, Outcome 3 Number needing cytotoxic agents.

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Analysis 4.4

Comparison 4 Cyclosporin and steroid therapy in first episode of childhood nephrotic syndrome, Outcome 4 Serum creatinine at end of study.

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Analysis 5.1

Comparison 5 Steroid therapy in relapse of nephrotic syndrome, Outcome 1 Number of children with further relapses by 9‐12 months.

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Analysis 5.2

Comparison 5 Steroid therapy in relapse of nephrotic syndrome, Outcome 2 Number of children relapsing during therapy.

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Analysis 5.3

Comparison 5 Steroid therapy in relapse of nephrotic syndrome, Outcome 3 Mean relapse rate/patient/year.

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Analysis 5.4

Comparison 5 Steroid therapy in relapse of nephrotic syndrome, Outcome 4 Mean time to relapse.

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Analysis 5.5

Comparison 5 Steroid therapy in relapse of nephrotic syndrome, Outcome 5 Cumulative steroid dose in g/m².

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Analysis 5.6

Comparison 5 Steroid therapy in relapse of nephrotic syndrome, Outcome 6 Serious adverse events.

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Analysis 5.7

Comparison 5 Steroid therapy in relapse of nephrotic syndrome, Outcome 7 Mean time to remission.

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Analysis 6.1

Comparison 6 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 1 Number with relapses.

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Analysis 6.2

Comparison 6 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 2 Number with frequently relapsing or steroid dependent nephrotic syndrome.

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Analysis 6.3

Comparison 6 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 3 Relapse rate/patient/year.

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Analysis 6.4

Comparison 6 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 4 Cumulative steroid dose in g/kg.

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Analysis 6.5

Comparison 6 Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome, Outcome 5 Adverse effects.

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Analysis 7.1

Comparison 7 Steroid therapy in first episode of childhood nephrotic syndrome, Outcome 1 Number of children relapsing by 12‐24 months after 3 months or more of prednisone versus 2 months.

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Analysis 7.2

Comparison 7 Steroid therapy in first episode of childhood nephrotic syndrome, Outcome 2 Number of children relapsing after 6 months of predisone therapy versus 3 months.

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Table 1. Electronic search strategies

Database	Search terms
CENTRAL	#1 (Nephrotic and syndrome) #2 Child #3 Nephrosis.ME #4 Nephrosis‐Lipoid.ME #5 Nephrotic ‐ Syndrome*.ME #6 #1 or #3 or #4 or #5 #7 #2 and #6
MEDLINE	1. exp nephrotic syndrome/ or nephrotic syndrome.tw. 2. exp nephrosis, lipoid/ or lipoid nephrosis.tw. 3. 1 or 2 4. exp child/ or child$.tw. 5. 3 and 4
EMBASE	1. exp nephrotic syndrome/ or nephrotic syndrome.tw. 2. exp steroid/ or steroids.tw 3. 1 and 2

Table 1. Electronic search strategies

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Table 2. Assessment of study quality in trials of steroid therapy in nephrotic syndrome

Diagnosis	Study ID	Allocation concealed	Intention‐to‐treat	Follow‐up complete	Investigator/patient	Outcome assessors
Initial episode of nephrotic syndrome	Kleinknecht 1982	Adequate	Unclear	0% lost to follow‐up at 1 year	No blinding	Not stated
	APN 1988	Adequate	No; 11.6% of 69 with SSNS withdrawn after randomisation	1.6% lost to follow‐up at 1 year	No blinding	Not stated
	Ueda 1988	Inadequate	Unclear	0% lost to follow‐up at 1 year	No blinding	Not stated
	APN 1993	adequate	No; 7.8% of 61 with SSNS withdrawn after randomisation	0% lost to follow‐up at 2 year	No blinding	Not stated
	Ksiazek 1995	Inadequate	Yes	0% lost to follow‐up at 1 year	No blinding	Not stated
	Norero 1996	Inadequate	No; 26% of 82 with SSNS withdrawn after randomisation excluded	0% lost to follow‐up at 1.5 years	No blinding	Not stated
	Bagga 1999	Adequate	No: 4% of 47 with SSNS withdrawn after randomisation	0% lost to follow‐up at 1 year	No blinding	Not stated
Relapse of nephrotic syndrome	ISKDC 1979	Unclear	No; 17% of 64 withdrawn after randomisation	5.5% lost to follow‐up at 6‐9 months	No blinding	Not stated
	APN 1981	Inadequate	No; 25% of 64 withdrawn after randomisation	0% lost to follow‐up at 1 year excluded	No blinding	Not stated
	Imbasciali 1985	Adequate	Yes	0% lost to follow‐up at 12‐24 months	No blinding	Not stated
	Ekka 1997	Unclear	Unclear	10% lost to follow‐up at 9 months	No blinding	Not stated
	Broyer 1997	Adequate	No; 2.5% withdrawn after randomisation	2.5% lost to follow‐up at 1 year	Both	Not stated
Additional studies (2002)	Hiraoka 2000	Unclear	Yes	1.6% lost to follow‐up at 2 years	No blinding	Not stated
	Jayantha 2002a	Adequate	No	11% lost to follow‐up in initial 3‐6 months & excluded from analysis	No blinding	No blinding
	Leisti 1978	Unclear	Unclear	0% lost to follow‐up	Both	Not stated
	Mattoo 2000	Inadequate	No	Children lost to follow‐up were excluded from analysis	No blinding	Not stated
	Yoshikawa 1998	Adequate	Unclear	7.7% of 196 did not complete 2 year follow‐up & excluded from analysis	No blinding	Not stated
	Jayantha 2002b	Adequate	No	20% of 95 lost to follow‐up at 1 year	No blinding	Not stated
	Sharma 2002	Adequate	No	4% of 156 lost to follow‐up	No blinding	Not stated
Additional studies (2004)	Hiraoka 2003	Adequate	Yes	3% of 70 SSNS lost to follow‐up	No blinding	Not stated
	APN VIII 1999	Adequate	No; 25% of 138 with SSNS withdrawn after randomisation	16% did not complete follow‐up	No blinding	Not stated
	Pecoraro 2003	Inadequate	No	Unclear	No blinding	Not stated
	Satomura 2001	Unclear	No	Unclear	No blinding	Not stated
Additional studies (2006)	Li 1994	Inadequate	Unclear	Unclear	No blinding	Not stated

Table 2. Assessment of study quality in trials of steroid therapy in nephrotic syndrome

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Table 3. Outcomes of trials in children with relapsing nephrotic syndrome

Study ID	Relapse on therapy	Relapse by 9 months	Relapse by 12 months	Mean relapse rate	Steroid therapy
	RR (95% CI)	RR (95% CI)	RR (95% CI)	MD (95% CI)
APN 1981	0.60 (0.36 to 1.02)		1.20 (0.93 to 1.55)	‐0.20 (‐0.65 to 0.25)	Alternate day versus intermittent
Broyer 1997			0.44 (0.25 to 0.78)	‐1.90 (‐2.77 to ‐1.03)	Deflazacort versus prednisone
Ekka 1997		1.07 (0.77 to 1.50)			Daily versus divided dose
Imbasciali 1985			1.06 (0.75 to 1.52)		IV and oral versus oral
ISKDC 1979	0.20 (0.05 to 0.82)	1.00 (0.89 to 1.12)		0.54 (‐0.50 to 1.58)	Daily versus intermittent
Jayantha 2002b			0.43 (0.29 to 0.65)	‐1.78 (‐2.30 to ‐1.26)	7 months therapy versus standard ISKDC regimen for relapse
Mattoo 2000				‐3.30 (‐4.03 to ‐2.57)	Daily versus alternate‐day in URTI

Table 3. Outcomes of trials in children with relapsing nephrotic syndrome

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Table 4. Expected relapse rates in groups of children with different control event rates

Treated for 2 months	Additional 1 month	Additional 5 months
Relapse rate when treated for 2 months	Reduction in relapse rate for each additional 1 month of therapy above 2 months	Relapse rate if treated for an additional 5 months (total 7 months)
80%	9%	35%
60%	7%	25%
40%	4%	20%
20%	2%	10%
10%	1%	5%

Table 4. Expected relapse rates in groups of children with different control event rates

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Comparison 1. Steroid therapy in first episode of nephrotic syndrome: comparisons with ISKDC standard therapy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number of children relapsing by 6 months Show forest plot	7		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Duration: 1 month versus 2 months (standard)	1	61	Risk Ratio (M‐H, Random, 95% CI)	1.60 [1.01, 2.54]
1.2 Duration: 3 months or more versus 2 months (standard)	5	400	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.28, 0.75]
1.3 Increased dose of prednisone versus standard dose	6	460	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.32, 0.71]
2 Number of children relapsing by 12‐24 months Show forest plot	9		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Duration: 1 month versus 2 months (standard)	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.46 [1.01, 2.12]
2.2 Duration: 3 months or more versus 2 months (standard)	6	422	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.58, 0.84]
2.3 Increased dose of prednisone versus standard dose	7	481	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.56, 0.80]
2.4 12 weeks (2240 mg/m²) versus 8 weeks (2520 mg/m²)	1	73	Risk Ratio (M‐H, Random, 95% CI)	1.24 [0.84, 1.85]
3 Mean relapse rate/patient/year Show forest plot	4		Mean Difference (IV, Random, 95% CI)	Subtotals only

3.1 Duration: 3 months or more versus 2 months (standard)	4	295	Mean Difference (IV, Random, 95% CI)	‐0.65 [‐1.29, ‐0.00]
4 Number with frequent relapses Show forest plot	8		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 Duration: 1 month versus 2 months (standard)	1	61	Risk Ratio (M‐H, Random, 95% CI)	1.48 [0.85, 2.59]
4.2 Duration: 3 months or more versus 2 months (standard)	6	452	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.46, 0.84]
4.3 Increased dose of prednisone versus standard dose (2240 mg/m²)	7	512	Risk Ratio (M‐H, Random, 95% CI)	0.64 [0.48, 0.84]
5 Cumulative steroid dose in g/m² Show forest plot	4		Mean Difference (IV, Random, 95% CI)	Subtotals only

5.1 Duration: 1 month versus 2 months (standard)	1	61	Mean Difference (IV, Random, 95% CI)	‐0.98 [‐1.28, ‐0.68]
5.2 Duration: 3 months or more versus 2 months (standard)	3	245	Mean Difference (IV, Random, 95% CI)	0.71 [‐0.67, 2.09]
6 Adverse events: increased prednisone dose versus standard duration Show forest plot	7		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

6.1 Psychological disorders	4	293	Risk Ratio (M‐H, Random, 95% CI)	2.44 [0.66, 9.06]
6.2 Hypertension	7	526	Risk Ratio (M‐H, Random, 95% CI)	1.60 [0.60, 4.28]
6.3 Opthalmological disorders	6	460	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.15, 4.42]
6.4 Retarded growth	4	354	Risk Ratio (M‐H, Random, 95% CI)	0.54 [0.25, 1.18]
6.5 Cushing's syndrome	4	292	Risk Ratio (M‐H, Random, 95% CI)	1.23 [0.78, 1.96]
6.6 Infections	2	172	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.53, 1.17]
6.7 Osteoporosis	3	233	Risk Ratio (M‐H, Random, 95% CI)	0.47 [0.06, 3.38]
7 Subgroup analysis: Relapse at 12‐24 months according to adequacy of allocation concealment Show forest plot	7		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

7.1 Adequate allocation concealment	3	204	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.51, 0.87]
7.2 Unclear or inadequate allocation concealment	4	277	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.55, 0.90]

Comparison 1. Steroid therapy in first episode of nephrotic syndrome: comparisons with ISKDC standard therapy

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Comparison 2. Steroid therapy in first episode of nephrotic syndrome: comparisons of 3 months or more of steroids

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number of children relapsing by 6 months Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Duration: 6 months versus 3 months	3	350	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.35, 0.64]
1.2 Duration: 12 months versus 5 months	1	58	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.32, 3.09]
2 Number of children relapsing by 12‐24 months Show forest plot	6		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Duration: 6 months versus 3 months	4	382	Risk Ratio (M‐H, Random, 95% CI)	0.57 [0.45, 0.71]
2.2 Duration: 12 months versus 5 months	1	58	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.51, 1.13]
2.3 High dose versus low dose given for same duration	2	91	Risk Ratio (M‐H, Random, 95% CI)	0.59 [0.42, 0.84]
3 Mean relapse rate/patient/year Show forest plot	2		Mean Difference (IV, Random, 95% CI)	Subtotals only

3.1 Duration: 6 months versus 3 months	2	280	Mean Difference (IV, Random, 95% CI)	‐0.44 [‐0.82, ‐0.07]
4 Number with frequent relapses Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 Duration: 6 months versus 3 months	3	350	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.39, 0.80]
5 Cumulative steroid dose in g/m² Show forest plot	2		Mean Difference (IV, Random, 95% CI)	Subtotals only

5.1 Duration: 6 months versus 3 months	2	280	Mean Difference (IV, Random, 95% CI)	‐1.55 [‐3.00, 1.90]
6 Adverse events: 6 months versus 3 months duration Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

6.1 Hypertension	3	349	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.65, 2.16]
6.2 Opthalmological	3	335	Risk Ratio (M‐H, Random, 95% CI)	0.39 [0.14, 1.08]
6.3 Infections	2	280	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.73, 1.62]
6.4 Cushing's syndrome	3	349	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.39, 1.59]
6.5 Gastrointestinal bleeding	1	140	Risk Ratio (M‐H, Random, 95% CI)	1.5 [0.26, 8.70]
6.6 Addisonian crisis	1	140	Risk Ratio (M‐H, Random, 95% CI)	0.5 [0.05, 5.39]
6.7 Psychological disorders	2	209	Risk Ratio (M‐H, Random, 95% CI)	0.08 [0.00, 1.45]
6.8 Growth	1	140	Risk Ratio (M‐H, Random, 95% CI)	1.26 [0.29, 5.42]
6.9 Osteoporosis	1	140	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 2. Steroid therapy in first episode of nephrotic syndrome: comparisons of 3 months or more of steroids

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Comparison 3. Steroid therapy and Sairei‐to in first episode of nephrotic syndrome

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Long prednisone & Sairei‐to versus standard prednisone & Sairei‐to Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

1.1 Relapse at 2 years	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.2 Number with frequent relapses at 2 years	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 3. Steroid therapy and Sairei‐to in first episode of nephrotic syndrome

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Comparison 4. Cyclosporin and steroid therapy in first episode of childhood nephrotic syndrome

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Relapse by 6 months Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

2 Relapse by 12 months Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

3 Number needing cytotoxic agents Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

4 Serum creatinine at end of study Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Comparison 4. Cyclosporin and steroid therapy in first episode of childhood nephrotic syndrome

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Comparison 5. Steroid therapy in relapse of nephrotic syndrome

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number of children with further relapses by 9‐12 months Show forest plot	5		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

1.1 Single versus divided dose therapy (2 months therapy)	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.2 Intermittent dose versus alternate‐day therapy (6 months therapy)	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.3 Intravenous versus oral therapy (6 months therapy)	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.4 Deflazacort versus prednisone (12 months therapy)	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.5 Prolonged oral versus intermittent therapy (2 months therapy )	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Number of children relapsing during therapy Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

2.1 Intermittent dose versus alternate‐day therapy (6 months therapy)	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.2 Daily versus intermittent therapy (2 months therapy)	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Mean relapse rate/patient/year Show forest plot	4		Mean Difference (IV, Random, 95% CI)	Totals not selected

3.1 Single versus divided dose therapy (2 months therapy)	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
3.2 Daily versus intermittent therapy (2 months therapy)	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
3.3 Deflazacort versus prednisone (12 months therapy)	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
3.4 Increased prednisone for URTI	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
4 Mean time to relapse Show forest plot	2		Mean Difference (IV, Random, 95% CI)	Totals not selected

4.1 Single versus divided dose therapy (2 months therapy)	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
4.2 Daily versus intermittent therapy (2 months therapy)	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
5 Cumulative steroid dose in g/m² Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

5.1 Single versus divided dose therapy (2 months therapy)	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
6 Serious adverse events Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

6.1 Single versus divided dose therapy (2 months duration)	2	138	Risk Ratio (M‐H, Random, 95% CI)	0.41 [0.18, 0.91]
7 Mean time to remission Show forest plot	2	138	Mean Difference (IV, Random, 95% CI)	0.04 [‐0.98, 1.06]

Comparison 5. Steroid therapy in relapse of nephrotic syndrome

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Comparison 6. Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number with relapses Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

1.1 Relapse by 6 months	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.2 Relapse by 12 months	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.3 Relapse by 2 years	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.4 Relapse by 3 years	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Number with frequently relapsing or steroid dependent nephrotic syndrome Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

3 Relapse rate/patient/year Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

3.1 Relapse rate at 1 year	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
3.2 Relapse rate at 2 years	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
3.3 Relapse rate at 3 years	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
4 Cumulative steroid dose in g/kg Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

4.1 After one year	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
4.2 After two years	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
4.3 After three years	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
5 Adverse effects Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

5.1 Number with hypertension	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.2 Number with growth failure	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 6. Prolonged steroid therapy (7 months) for relapsing nephrotic syndrome

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Comparison 7. Steroid therapy in first episode of childhood nephrotic syndrome

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number of children relapsing by 12‐24 months after 3 months or more of prednisone versus 2 months Show forest plot	6	422	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.58, 0.84]

2 Number of children relapsing after 6 months of predisone therapy versus 3 months Show forest plot	4	382	Risk Ratio (M‐H, Random, 95% CI)	0.57 [0.45, 0.71]

Comparison 7. Steroid therapy in first episode of childhood nephrotic syndrome

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