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BMJ Open 2013 Nezu
BMJ Open 2013 Nezu
BMJ Open 2013 Nezu
com
Open Access
Research
To cite: Nezu U,
Kamiyama H, Kondo Y, et al.
Effect of low-protein diet on
kidney function in diabetic
nephropathy:
meta-analysis of randomised
controlled trials. BMJ Open
2013;3:e002934.
doi:10.1136/bmjopen-2013002934
Prepublication history and
additional material for this
paper are available online. To
view these files please visit
the journal online
(http://dx.doi.org/10.1136/
bmjopen-2013-002934).
Received 25 March 2013
Accepted 25 April 2013
ABSTRACT
Objective: To evaluate the effect of low-protein diet
on kidney function in patients with diabetic
nephropathy.
Design: A systematic review and a meta-analysis of
randomised controlled trials.
Data sources: MEDLINE, EMBASE, Cochrane Library,
ClinicalTrials.gov, International Standard Randomised
Controlled Trial Number (ISRCTN) Register and University
Hospital Medical Information Network-Clinical Trials
Registry (UMIN-CTR) from inception to 10 December
2012. Internet searches were also carried out with general
search engines (Google and Google Scholar).
Study selection: Randomised controlled trials that
compared low-protein diet versus control diet and
assessed the effects on kidney function, proteinuria,
glycaemic control or nutritional status.
ARTICLE SUMMARY
Article focus
Our research question is whether low-protein
diet treatment is beneficial or not in patients with
diabetic nephropathy.
Our hypothesis was that low-protein diet
improves kidney function, but this effect is
affected by patients actual compliance with diet
treatment.
Key messages
A low-protein diet significantly improved kidney
function in patients with diabetic nephropathy.
This effectiveness was observed only when
patients diet compliance was fair; however, the
successful treatment may not need to be as
stringent as the current clinical guidelines
recommend.
INTRODUCTION
Diabetic nephropathy is the leading cause of
end-stage renal disease necessitating renal
replacement therapy1 2 and is also associated
with increased risk of cardiovascular
Author (year)
Subjects (n)
Male (n)
Age (years)
BMI (kg/m2)
Koya (2009)
Velzquez (2008)
112
60
59
40
57
67
24.6
27.7
T2
T2
17
Dussol (2005)
47
83
52
Mixed
15
Meloni (2004)
Brinkworth (2004)
80
38
48
39
55
62
33.5
Mixed
T2
17
Hansen (2002)
Pijls (2002)
72
131
65
58
41
66
25.0
27.8
T1
T2
28
7
Pijls (1999)
121
61
63
27.7
T2
Raal (1994)
Dullaart (1993)
Zeller (1991)
Brouhard (1990)
22
30
35
15
36
90
60
9
30
41
34
33
24.9
24.1
T1
T1
T1
T1
20
23
22
19
Ciavarella (1987)
16
56
37
T1
18
BMI, body mass index; GFR, glomerular filtration rate; HbA1c, haemoglobin A1C; T1, type 1; T2, type 2.
Nephropathy
stage
Macroalbuminuria
Normoalbuminuria,
microalbuminuria
or
macroalbuminuria
Microalbuminuria
or
macroalbuminuria
Macroalbuminuria
Normoalbuminuria
or
microalbuminuria
Macroalbuminuria
Normoalbuminuria
or
microalbuminuria
Normoalbuminuria
or
microalbuminuria
Macroalbuminuria
Microalbuminuria
Macroalbuminuria
Microalbuminuria
or
macroalbuminuria
Macroalbuminuria
GFR (ml/min/
1.73 m2)
HbA1c
(%)
Intervention
period
(months)
62
55
8.1
8.3
60
4
38
8.1
24
100
7.0
6.4
12
3
62
86
9.8
7.7
48
28
82
7.7
12
84
68
126
47
13.0
7.8
7.9
7.3
6
24
35
12
100
8.9
4.5
Duration of
diabetes
(years)
Type of
diabetes
Koya (2009)
Velzquez (2008)
Dussol (2005)
Meloni (2004)
Brinkworth (2004)
56
29
22
40
19
Hansen (2002)
Pijls (2002)
Pijls (1999)
Raal (1994)
Dullaart (1993)
Zeller (1991)
Brouhard (1990)
Ciavarella (1987)
Prescription*
Control
Subjects
(n)
Prescription*
1.0 vs 1.0
0.82 vs 1.2
1.10 vs 1.03
0.86 vs 1.24
1.0
0.68
1.07
0.69
FR
RT (24 h)
FQ
FQ
UUN/Cre
0.9 vs 1.1
56.0 vs 80.7 (g/day)
68 vs 84 (g/day)
0.86 vs 1.24
35.6 vs 42.9 (mg/mg)
0.8
34
68
63
11
16
1.2
1.01.2
1.2
Free
30% of energy from
protein
As usual
As usual
As usual
1.6
As usual
0.89 vs 1.02
1.1 vs 1.14
1.12 vs 1.15
0.87 vs 2.0
0.79 vs 1.09
0.87
0.96
0.97
0.44
0.72
FQ
FQ
RT
(1 week)
15
7
9
>1.0
As usual
1.44
0.72 vs 1.08
0.67
24 h UUN
4 h UUN
0.93 vs 1.12
value not described
Animal protein, 5 vs 10
(energy %)
Vegetable protein, 6 vs 6
(energy %)
56
31
25
40
19
38
63
58
11
14
0.8
0.60.8
0.8
0.8
15% of energy
from protein
0.6
0.8
0.8
0.8
0.6
20
8
7
0.6
0.6
0.71
0.6
0.6
Author (year)
LPD
Subjects
(n)
Actual protein
intake based on
Actual protein intake based on alternative
24 h UUN*
methods*
LPD vs
control*
APIR Method
LPD vs control*
APIR
6
Table 2 Details of diet prescription and compliance assessment
Subgroups
Mean difference
(95% CI)
I2 (%)
Proteinuria
Number of
p Value* comparisons
Mean difference
(95% CI)
I2 (%)
p Value*
6
3
4
0.57
8
3
4
<0.0001
6
5
2
94
87
0
0.05
6
6
3
0.002
0.03
86
3
1
32
89
2
2
0.001
95
7
6
92
92
0.06
8
7
92
90
0.89
5
8
85
92
0.50
6
9
91
91
0.95
9
4
94
0
0.006
10
5
91
76
0.1
4
7
3
1
12
92
14
11
93
12
91
<0.00001
BMI
Overweight or obese (BMI 25)
Healthy weight (BMI <25)
Unknown
Type of diabetes
T1DM
T2DM
Mixed
Nephropathy stage
Normoalbuminuria or mix of
normoalbuminuria and
microalbuminuria
Microalbuminuria
Mix of microalbuminuria and
macroalbuminuria
Macroalbuminuria
Intervention period
Short (623 months)
Long (24 months)
Overall risk of bias
High (risk score 48)
Low (risk score 13)
Diet compliance:
Fair (APIR <0.9)
Poor (APIR 0.9)
Measurement index of proteinuria
Proteinuria (g/24 h)
Albuminuria (mg/24 h)
Albuminuria (g/min)
Albumin/Cre ratio (mg/mmol)
Sensitivity analysis
Excluding a subgroup of
normoalbuminuria with separate
data
Excluding studies including
normoalbuminuria
GFR
Number of
comparisons
8
Table 3 Subgroup analyses and sensitivity analyses for clinical characteristics and study quality
10.
12.
11.
13.
14.
15.
16.
Author affiliations
1
Department of Clinical Pharmacology & Therapeutics, University of the
Ryukyus, Okinawa, Japan
2
Department of Endocrinology & Metabolism, Yokohama City University
Graduate School of Medicine, Kanagawa, Japan
3
Department of Endocrinology & Metabolism, Chigasaki Municipal Hospital,
Kanagawa, Japan
4
Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
Contributors UN had the idea for the study and designed the method of this
meta-analysis including the inclusion and exclusion criteria, conducted data
collection and extraction, wrote the first draft of the report and did the
statistical analysis with guidance from MS and TM. UN and HK searched the
articles and assessed their eligibility. When discrepancies occurred, the
eligibility of the articles was discussed by the committee consisting of UN,
MS, TM and SU. TM did the major revision and also made comments. All
other authors commented on the draft and approved the final version of the
manuscript. UN and SU are the guarantors.
Funding This research received no specific grant from any funding agency in
the public, commercial or not-for-profit sectors.
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doi: 10.1136/bmjopen-2013-002934
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References
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http://bmjopen.bmj.com/content/3/5/e002934#BIBL
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