To determine whether a low-protein diet slows the decrease in glomerular filtration rate (GFR) and decreases the albumin excretion rate (AER) in diabetic patients with incipient and overt nephropathy.
- Age 18 years to 75 years
- Type 1 or type 2 diabetes with disease duration of at least 10 years
- Diabetic nephropathy
- Incipient: At least two microalbuminuria levels more than 30mg per day
- Overt: At least two macroalbuminuria levels more than 300mg per day.
- End-stage renal disease
- Pregnancy
- Cachexia
- Body mass index more than 33.
Recruitment: 63 patients of one physician
Design: Prospective, randomized, non-blinded clinical trial
Blinding used: Blinding could not be used as both subjects and investigators could identify dietary assignment.
Intervention
- Group One: Low-protein diet of 0.8g per kilogram body weight per day
- Group Two: Usual protein diet, adjusted to 1.2g per kilogram body weight per day if higher.
Statistical Analysis
- Mann-Whitney U for qualitative variables
- Chi-square test for quantitative variables
- First intention-to-treat analysis followed by best case analysis.
Timing of Measurements
- Major outcome variables (GFR and AER) at baseline, 12 months and 24 months
- Biochemical measurements every three months.
Dependent Variables
- GFR: Diethylene triamine penta-acetic acid clearance
- Urinary albumin: Nephelometry.
Independent Variables
Dietary protein intake (low-protein vs. usual-protein): Maroni equation using 24-hour urine collection, supported by a seven-day food frequency.
Control Variable
Blood pressure.
- Initial N: 63
- Attrition (final N): 47
- Age: Usual protein group: 63y±9y; low-protein group: 52y±12y
- Ethnicity: Not given.
Other Relevant Demographics
- Sex: Usual-protein group, eight men and 17 women; low-protein group, 19 men and three women
- Diabetes (type 1/type 2): Usual-protein group, eight with type 1 and 17 with type 2; low-protein group, two with type 1 and 20 with type 2
- Baseline GFR (ml per minute per 1.73 m2): Usual-protein diet group, 89±27; low-protein diet group, 82±21.
Anthropometrics
Only age was different between groups.
Location
Hospital clinic, Marseille, France.
Variables |
Usual-Protein Group (N=25) |
Low-Protein Group (N=22) |
Statistical Significance of Group Difference |
Protein Intake (g/kg/day) at Two Years |
1.03±0.15
|
1.10±0.20
|
NS |
Change in GFR (ml/minute/1.73m2) at Two Years |
-5±15 |
-7±11 |
NS |
Change in Microalbuminuria (mg/day) |
+114±364 |
+156±486 |
NS |
BMI (kg/m2) |
+2
|
-1
|
NS |
Serum Albumin (g/L) |
-4
|
-4
|
NS |
Nutrient Intakes Food Questionnaire
Usual Protein
|
Low Protein
|
|||
Base
|
Two years
|
Base
|
Two years
|
|
Energy (kcal/day) |
1,824±490
|
1,855±620
|
1,685±380
|
1,704±276
|
Protein (g/day) |
87±20
|
84±26
|
79±20
|
67±14
|
Animal Protein (g/day) |
64±18
|
60±21
|
60±16
|
42±15
|
Protein (percentage kcal) |
21±5
|
19±4
|
20±3
|
16±3
|
Carbohydrate (g/day) |
173±70
|
171±65
|
168±52
|
184±44
|
Carbohydrate (percentage kcal) |
36±10
|
37±8
|
38±8
|
42±7
|
Fat (g/day) |
79±22
|
80±30
|
70±18
|
69±13
|
Fat (percentage kcal) |
39±6
|
39±7
|
38±6
|
37±6
|
Other Findings
Analysis of best-case scenario: Six low-protein and 12 usual-protein patients also found no differences.
A two-year low-protein diet did not alter the course of GFR and AER in diabetic patients with incipient or overt nephropathy receiving renin-angiotensin blockers with strict blood pressure control.
Other: | not reported |
- Investigators found no difference in dietary protein intake based on body weight between the two groups
- Dietary assessment was only done twice during the two-year trial
- Patients assigned to the low-protein diet had reduced caloric intake at these assessment, suggesting they reduced protein by reducing caloric intake on days they knew they would be monitored
- It is significant that only six of the 22 finishing patients assigned to the low-protein diet were considered compliant based on both FF and urinary N measures
- Conclusion is that the diet failed because few people followed it.
Quality Criteria Checklist: Primary Research
|
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Relevance Questions | |||
1. | Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) | Yes | |
2. | Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? | Yes | |
3. | Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? | Yes | |
4. | Is the intervention or procedure feasible? (NA for some epidemiological studies) | Yes | |
Validity Questions | |||
1. | Was the research question clearly stated? | Yes | |
1.1. | Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? | Yes | |
1.2. | Was (were) the outcome(s) [dependent variable(s)] clearly indicated? | Yes | |
1.3. | Were the target population and setting specified? | Yes | |
2. | Was the selection of study subjects/patients free from bias? | Yes | |
2.1. | Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? | Yes | |
2.2. | Were criteria applied equally to all study groups? | Yes | |
2.3. | Were health, demographics, and other characteristics of subjects described? | Yes | |
2.4. | Were the subjects/patients a representative sample of the relevant population? | Yes | |
3. | Were study groups comparable? | Yes | |
3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | Yes | |
3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | Yes | |
3.3. | Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) | Yes | |
3.4. | If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? | Yes | |
3.5. | If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) | N/A | |
3.6. | If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? | N/A | |
4. | Was method of handling withdrawals described? | Yes | |
4.1. | Were follow-up methods described and the same for all groups? | ??? | |
4.2. | Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) | Yes | |
4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | No | |
4.4. | Were reasons for withdrawals similar across groups? | Yes | |
4.5. | If diagnostic test, was decision to perform reference test not dependent on results of test under study? | N/A | |
5. | Was blinding used to prevent introduction of bias? | N/A | |
5.1. | In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? | N/A | |
5.2. | Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) | N/A | |
5.3. | In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? | N/A | |
5.4. | In case control study, was case definition explicit and case ascertainment not influenced by exposure status? | N/A | |
5.5. | In diagnostic study, were test results blinded to patient history and other test results? | N/A | |
6. | Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? | Yes | |
6.1. | In RCT or other intervention trial, were protocols described for all regimens studied? | Yes | |
6.2. | In observational study, were interventions, study settings, and clinicians/provider described? | N/A | |
6.3. | Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? | Yes | |
6.4. | Was the amount of exposure and, if relevant, subject/patient compliance measured? | Yes | |
6.5. | Were co-interventions (e.g., ancillary treatments, other therapies) described? | Yes | |
6.6. | Were extra or unplanned treatments described? | N/A | |
6.7. | Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? | Yes | |
6.8. | In diagnostic study, were details of test administration and replication sufficient? | N/A | |
7. | Were outcomes clearly defined and the measurements valid and reliable? | Yes | |
7.1. | Were primary and secondary endpoints described and relevant to the question? | Yes | |
7.2. | Were nutrition measures appropriate to question and outcomes of concern? | Yes | |
7.3. | Was the period of follow-up long enough for important outcome(s) to occur? | Yes | |
7.4. | Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? | Yes | |
7.5. | Was the measurement of effect at an appropriate level of precision? | Yes | |
7.6. | Were other factors accounted for (measured) that could affect outcomes? | Yes | |
7.7. | Were the measurements conducted consistently across groups? | Yes | |
8. | Was the statistical analysis appropriate for the study design and type of outcome indicators? | Yes | |
8.1. | Were statistical analyses adequately described and the results reported appropriately? | Yes | |
8.2. | Were correct statistical tests used and assumptions of test not violated? | Yes | |
8.3. | Were statistics reported with levels of significance and/or confidence intervals? | Yes | |
8.4. | Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? | Yes | |
8.5. | Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? | N/A | |
8.6. | Was clinical significance as well as statistical significance reported? | Yes | |
8.7. | If negative findings, was a power calculation reported to address type 2 error? | Yes | |
9. | Are conclusions supported by results with biases and limitations taken into consideration? | Yes | |
9.1. | Is there a discussion of findings? | Yes | |
9.2. | Are biases and study limitations identified and discussed? | Yes | |
10. | Is bias due to study's funding or sponsorship unlikely? | Yes | |
10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
10.2. | Was the study free from apparent conflict of interest? | Yes | |