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Flow chart of study selection process
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Figure 1

Flow chart of study selection process

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Comparison 1 Net change with altering salt diet, Outcome 1 Systolic BP.
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Analysis 1.1

Comparison 1 Net change with altering salt diet, Outcome 1 Systolic BP.

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Comparison 1 Net change with altering salt diet, Outcome 2 Diastolic BP.
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Analysis 1.2

Comparison 1 Net change with altering salt diet, Outcome 2 Diastolic BP.

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Comparison 1 Net change with altering salt diet, Outcome 3 Systolic BP (excluding Houlihan_Losartan 2002).
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Analysis 1.3

Comparison 1 Net change with altering salt diet, Outcome 3 Systolic BP (excluding Houlihan_Losartan 2002).

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Comparison 1 Net change with altering salt diet, Outcome 4 Diastolic BP (excluding Houlihan_Losartan 2002).
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Analysis 1.4

Comparison 1 Net change with altering salt diet, Outcome 4 Diastolic BP (excluding Houlihan_Losartan 2002).

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Comparison 1 Net change with altering salt diet, Outcome 5 MAP.
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Analysis 1.5

Comparison 1 Net change with altering salt diet, Outcome 5 MAP.

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Comparison 1 Net change with altering salt diet, Outcome 6 SCr.
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Analysis 1.6

Comparison 1 Net change with altering salt diet, Outcome 6 SCr.

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Comparison 1 Net change with altering salt diet, Outcome 7 CrCl.
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Analysis 1.7

Comparison 1 Net change with altering salt diet, Outcome 7 CrCl.

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Comparison 1 Net change with altering salt diet, Outcome 8 GFR.
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Analysis 1.8

Comparison 1 Net change with altering salt diet, Outcome 8 GFR.

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Comparison 1 Net change with altering salt diet, Outcome 9 ERPF.
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Analysis 1.9

Comparison 1 Net change with altering salt diet, Outcome 9 ERPF.

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Comparison 1 Net change with altering salt diet, Outcome 10 Proteinuria.
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Analysis 1.10

Comparison 1 Net change with altering salt diet, Outcome 10 Proteinuria.

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Comparison 1 Net change with altering salt diet, Outcome 11 HbA1c.
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Analysis 1.11

Comparison 1 Net change with altering salt diet, Outcome 11 HbA1c.

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Comparison 1 Net change with altering salt diet, Outcome 12 Weight.
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Analysis 1.12

Comparison 1 Net change with altering salt diet, Outcome 12 Weight.

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Comparison 1 Net change with altering salt diet, Outcome 13 BMI.
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Analysis 1.13

Comparison 1 Net change with altering salt diet, Outcome 13 BMI.

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Comparison 2 Net change in BP in type 1 and type 2 diabetes, Outcome 1 Systolic BP.
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Analysis 2.1

Comparison 2 Net change in BP in type 1 and type 2 diabetes, Outcome 1 Systolic BP.

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Comparison 2 Net change in BP in type 1 and type 2 diabetes, Outcome 2 Diastolic BP.
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Analysis 2.2

Comparison 2 Net change in BP in type 1 and type 2 diabetes, Outcome 2 Diastolic BP.

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Comparison 2 Net change in BP in type 1 and type 2 diabetes, Outcome 3 MAP.
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Analysis 2.3

Comparison 2 Net change in BP in type 1 and type 2 diabetes, Outcome 3 MAP.

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Comparison 2 Net change in BP in type 1 and type 2 diabetes, Outcome 4 HbA1c.
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Analysis 2.4

Comparison 2 Net change in BP in type 1 and type 2 diabetes, Outcome 4 HbA1c.

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Comparison 3 Net change in BP in hypertensive and normotensive participants, Outcome 1 Systolic BP.
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Analysis 3.1

Comparison 3 Net change in BP in hypertensive and normotensive participants, Outcome 1 Systolic BP.

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Comparison 3 Net change in BP in hypertensive and normotensive participants, Outcome 2 Diastolic BP.
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Analysis 3.2

Comparison 3 Net change in BP in hypertensive and normotensive participants, Outcome 2 Diastolic BP.

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Comparison 3 Net change in BP in hypertensive and normotensive participants, Outcome 3 MAP.
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Analysis 3.3

Comparison 3 Net change in BP in hypertensive and normotensive participants, Outcome 3 MAP.

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Table 1. Summary table of characteristics of included studies

Study

Number of participants

Age (years)

Males (%)

Diabetes

Study design

Blinding

Study duration (weeks)

Initial BP (SE)

Dodson_P 1989

34

61

71/65

Type 2

P

SB

12

180(18)/91(11)

Dodson_X 1989

9

62

67

Type 2

X

DB

4

160(20)/88(11)

Miller 1995

9

26

100

Type 1

X

SB

1

‐‐

Mulhauser 1996

14

31

75

Type 1

P

DB

4

‐‐

De'oliveira 1997

19

55

84

Type 2

P

NS

1

MAP 102(3)

Lopes De Faria 1997

10

30

70

Type 1

X

NS

1

MAP 91(9)

Miller 1997

12

23

100

Type 1

X

SB

1

MAP 82(4)

Petrie 1998

9

57

89

Type 2

X

DB

5 days

148(25)/82(7)

Trevisan_Normo 1998

9

42

67

Type 1

X

NS

1

120/72

Trevisan_Micro 1998

7

38

86

Type 1

X

NS

1

125/78

Yoshioka_Normo 1998

8

60

58

Type 2

X

NS

1

134(5)/78(1)

Yoshioka_Micro 1998

7

58

58

Type 2

X

NS

1

133(6)/75(4)

Yoshioka_Adva_alb 1998

4

51

58

Type 2

X

NS

1

131(4)/75(4)

Imanishi_Normo 2001

8

59

63

Type 2

X

SB

1

132(11)/73(7)

Imanishi_Micro 2001

8

61

50

Type 2

X

SB

1

136(9)/82(6)

Houlihan_Placebo 2002

10

63

90

Type 2

X

SB

2

MAP 111(3)

Houlihan_Losartan 2002

10

61

100

Type 2

X

SB

2

MAP 114(3)

Luik 2002

24

29

63

Type 1

X

NS

1

‐‐

Vedovato_Normo 2004

21

60

75

Type 2

X

NS

1

125(2)/79(2)

Yoshioka_Micro 1998

20

57

75

Type 2

X

NS

1

130(2)/80(2)

DB ‐ double‐blind; NS ‐ not stated; P ‐ parallel; X ‐ crossover; SB ‐ single blind; SE ‐ standard error

Figures and Tables -
Table 1. Summary table of characteristics of included studies
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Table 2. Outcomes reported in the included studies

Study

Urinary sodium (24h)

SCr

CrCl or GFR

RPF

Urinary albumin or protein (24h)

ACR

BP

HbA1c

BMI

Dodson_P 1989

X

X

X

Dodson_X 1989

X

X

X

Miller 1995

X

X

Mulhauser 1996

X

X

X

X

X

X

X

X

De'oliveira 1997

X

X

X

X

Lopes De Faria 1997

X

X

X

X

X

Miller 1997

X

X

X

X

Petrie 1998

X

X

Trevisan_Micro 1998; Trevisan_Normo 1998

X

X

X

X

X

Yoshioka_Adva_alb 1998; Yoshioka_Micro 1998; Yoshioka_Normo 1998

X

X

X

Imanishi_Micro 2001; Imanishi_Normo 2001

X

X

X

X

Houlihan_Losartan 2002; Houlihan_Placebo 2002

X

X

X

X

X

X

X

Luik 2002

X

X

X

X

X

X

X

X

X

Vedovato_Micro 2004; Vedovato_Normo 2004

X

X

X

ACR ‐ albumin‐creatinine ratio; BMI ‐ body mass index; CrCl ‐ creatinine clearance; GFR ‐ glomerular filtration rate; HbA1c ‐ glycated haemoglobin; RPF ‐ renal plasma flow; SCr ‐ serum creatinine

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Table 2. Outcomes reported in the included studies
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Table 3. Measurements of urine albumin and protein excretion in included studies

Study

Urine measurement

Change from high/normal salt to low salt

Significance

Mulhauser 1996

Reported as proteinuria

‐412.6 mg/d (‐1035 to 210)

NS

Houlihan_Placebo 2002

Reported as % change in geometric mean of albumin excretion (tolerance factor)

+38.5% (CI ‐31.7 to 108.8)

NS

Houlihan_Losartan 2002

‐43.5% (CI ‐77.5 to ‐9.6)

P = 0.02

Luik 2002

Reported as mg/24h of albumin

+1.4 mg/24 h

NS

Vedovato_Normo 2004

Reported as median of albumin (IQR)

9 (6 to 12) µg/min to 8 (5 to 12) µg/min

NS

Vedovato_Micro 2004

108 (84 to 178) µg/min to 80 (37 to 108) µg/min

P < 0.001

IQR ‐ intraquartile range; NS ‐ not significant
Figures and Tables -
Table 3. Measurements of urine albumin and protein excretion in included studies
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Comparison 1. Net change with altering salt diet

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Systolic BP Show forest plot

11

Mean Difference (Fixed, 95% CI)

‐7.04 [‐8.71, ‐5.38]

1.1 Long‐term studies

5

Mean Difference (Fixed, 95% CI)

‐6.20 [‐9.98, ‐2.43]

1.2 Short‐term studies

6

Mean Difference (Fixed, 95% CI)

‐7.25 [‐9.10, ‐5.40]

2 Diastolic BP Show forest plot

11

Mean Difference (Fixed, 95% CI)

‐3.03 [‐3.95, ‐2.11]

2.1 Long‐term studies

5

Mean Difference (Fixed, 95% CI)

‐3.78 [‐5.73, ‐1.84]

2.2 Short‐term studies

6

Mean Difference (Fixed, 95% CI)

‐2.82 [‐3.86, ‐1.78]

3 Systolic BP (excluding Houlihan_Losartan 2002) Show forest plot

10

Mean Difference (Fixed, 95% CI)

‐6.91 [‐8.61, ‐5.20]

3.1 Long‐term studies

4

Mean Difference (Fixed, 95% CI)

‐5.02 [‐9.38, ‐0.65]

3.2 Short‐term studies

6

Mean Difference (Fixed, 95% CI)

‐7.25 [‐9.10, ‐5.40]

4 Diastolic BP (excluding Houlihan_Losartan 2002) Show forest plot

10

Mean Difference (Fixed, 95% CI)

‐2.76 [‐3.73, ‐1.79]

4.1 Long‐term studies

4

Mean Difference (Fixed, 95% CI)

‐2.38 [‐5.00, 0.24]

4.2 Short‐term studies

6

Mean Difference (Fixed, 95% CI)

‐2.82 [‐3.86, ‐1.78]

5 MAP Show forest plot

11

Mean Difference (Fixed, 95% CI)

‐2.19 [‐3.32, ‐1.06]

5.1 Long‐term studies

2

Mean Difference (Fixed, 95% CI)

‐4.98 [‐8.27, ‐1.69]

5.2 Short‐term studies

9

Mean Difference (Fixed, 95% CI)

‐1.82 [‐3.02, ‐0.62]

6 SCr Show forest plot

2

Mean Difference (Fixed, 95% CI)

‐0.52 [‐4.74, 3.71]

7 CrCl Show forest plot

5

Mean Difference (Fixed, 95% CI)

‐6.33 [‐10.47, ‐2.19]

8 GFR Show forest plot

10

Mean Difference (Fixed, 95% CI)

‐1.92 [‐4.49, 0.64]

8.1 Long‐term studies

3

Mean Difference (Fixed, 95% CI)

‐2.41 [‐5.97, 1.14]

8.2 Short‐term studies

7

Mean Difference (Fixed, 95% CI)

‐1.39 [‐5.10, 2.32]

9 ERPF Show forest plot

8

Mean Difference (Fixed, 95% CI)

‐1.17 [‐3.25, 0.92]

9.1 Long‐term studies

3

Mean Difference (Fixed, 95% CI)

‐0.73 [‐2.83, 1.37]

9.2 Short‐term studies

5

Mean Difference (Fixed, 95% CI)

‐31.58 [‐49.14, ‐14.02]

10 Proteinuria Show forest plot

1

Mean Difference (Fixed, 95% CI)

Totals not selected

11 HbA1c Show forest plot

6

Mean Difference (Fixed, 95% CI)

‐0.15 [‐0.31, 0.01]

11.1 Long‐term studies

4

Mean Difference (Fixed, 95% CI)

‐0.05 [‐0.35, 0.25]

11.2 Short‐term studies

2

Mean Difference (Fixed, 95% CI)

‐0.19 [‐0.38, ‐0.00]

12 Weight Show forest plot

11

Mean Difference (Fixed, 95% CI)

‐1.01 [‐1.20, ‐0.82]

12.1 Long‐term studies

3

Mean Difference (Fixed, 95% CI)

‐0.24 [‐1.57, 1.09]

12.2 Short‐term studies

8

Mean Difference (Fixed, 95% CI)

‐1.03 [‐1.22, ‐0.83]

13 BMI Show forest plot

4

Mean Difference (Fixed, 95% CI)

‐0.40 [‐0.53, ‐0.28]
Figures and Tables -
Comparison 1. Net change with altering salt diet
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Comparison 2. Net change in BP in type 1 and type 2 diabetes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Systolic BP Show forest plot

11

Mean Difference (Fixed, 95% CI)

‐7.04 [‐8.71, ‐5.38]

1.1 Type 1 diabetes

4

Mean Difference (Fixed, 95% CI)

‐7.11 [‐9.13, ‐5.10]

1.2 Type 2 diabetes

7

Mean Difference (Fixed, 95% CI)

‐6.90 [‐9.84, ‐3.95]

2 Diastolic BP Show forest plot

11

Mean Difference (Fixed, 95% CI)

‐3.03 [‐3.95, ‐2.11]

2.1 Type 1 diabetes

4

Mean Difference (Fixed, 95% CI)

‐3.13 [‐4.28, ‐1.98]

2.2 Type 2 diabetes

7

Mean Difference (Fixed, 95% CI)

‐2.87 [‐4.39, ‐1.35]

3 MAP Show forest plot

11

Mean Difference (Fixed, 95% CI)

‐2.19 [‐3.32, ‐1.06]

3.1 Type 1 diabetes

3

Mean Difference (Fixed, 95% CI)

0.09 [‐1.83, 2.00]

3.2 Type 2 diabetes

8

Mean Difference (Fixed, 95% CI)

‐3.40 [‐4.80, ‐2.00]

4 HbA1c Show forest plot

6

Mean Difference (Fixed, 95% CI)

‐0.15 [‐0.31, 0.01]

4.1 Type 1 diabetes

3

Mean Difference (Fixed, 95% CI)

‐0.16 [‐0.32, 0.01]

4.2 Type 2 diabetes

3

Mean Difference (Fixed, 95% CI)

‐0.12 [‐0.58, 0.34]
Figures and Tables -
Comparison 2. Net change in BP in type 1 and type 2 diabetes
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Comparison 3. Net change in BP in hypertensive and normotensive participants

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Systolic BP Show forest plot

11

Mean Difference (Fixed, 95% CI)

‐7.04 [‐8.71, ‐5.38]

1.1 Hypertensive

6

Mean Difference (Fixed, 95% CI)

‐4.86 [‐8.31, ‐1.41]

1.2 Normotensive

5

Mean Difference (Fixed, 95% CI)

‐7.70 [‐9.60, ‐5.81]

2 Diastolic BP Show forest plot

11

Mean Difference (Fixed, 95% CI)

‐3.03 [‐3.95, ‐2.11]

2.1 Hypertensive

6

Mean Difference (Fixed, 95% CI)

‐2.96 [‐4.81, ‐1.11]

2.2 Normotensive

5

Mean Difference (Fixed, 95% CI)

‐3.06 [‐4.11, 0.00]

3 MAP Show forest plot

11

Mean Difference (Fixed, 95% CI)

‐2.19 [‐3.32, ‐1.06]

3.1 Hypertensive

3

Mean Difference (Fixed, 95% CI)

‐5.25 [‐8.43, ‐2.07]

3.2 Normotensive

8

Mean Difference (Fixed, 95% CI)

‐1.75 [‐2.96, ‐0.54]
Figures and Tables -
Comparison 3. Net change in BP in hypertensive and normotensive participants
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