Citation:

Dussol B, Iovanna C, Raccah D, Damon P, Morange S, Vague P, Vialettes S, Oliver C, Loundoun A, Berland Y. A randomized trial of low-protein diet in type 1 and in type 2 diabetes mellitus patients with incipient and overt nephropathy. J Renal Nutr. 2005; 15: 398-406.

PubMed ID: 16198932
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

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.

Inclusion Criteria:
  • 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.
Exclusion Criteria:
  • End-stage renal disease
  • Pregnancy
  • Cachexia
  • Body mass index more than 33.
Description of Study Protocol:

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.
Data Collection Summary:

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.

Description of Actual Data Sample:
  • 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.

Summary of Results:

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.

Author Conclusion:

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.

Funding Source:
Other: not reported
Reviewer Comments:
  • 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
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