DM: Protein Amount (2014)

Citation:

Hansen HP, Tauber-Lassen E, Jensen BR, Parving H-H. Effect of dietary protein restriction on prognosis in patients with diabetic nephropathy.  Kidney Int 2002:61:220-228.

PubMed ID: 12081581
 
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 the effect of dietary protein restriction on survival, progress to ESRD and glomerular filtration rate decline in diabetic nephropathy.
Inclusion Criteria:
  • 18-60 y
  • type 1 diabetes for at least 10 y with onset before the age of 35 y
  • presence of diabetic retinopathy
  • albuminuria > 300 mg/24 h in at least 2 of 3 urine samples
  • no clinical or laboratory evidence of other kidney or urinary tract disease
  • GFR above 20 mL/min/1.73 m2
  • pre-study decline in GFR > 2 mL/min/1.73 m2

 

Exclusion Criteria:
  • pregnancy
  • history of congestive heart failure, myocardial infarction or coronary bypass surgery within the last 3 months
Description of Study Protocol:

Recruitment - Steno Diabetes Center patients meeting criteria.  82 patients fulfilling criteria were consecutively entered between May 1995 and April 1996.

Design - Randomized Controlled Trial.

Blinding used (if applicable) - Diet studies could not be blinded. 

Intervention (if applicable) - Randomized to low protein diet (0.6 g/kg/d protein followed for 4 years or until death) or usual protein diet.

Statistical Analysis - Linear regression analysis used to estimate rate of decline in GFR.  Intention to treat approach used to relate levels of decline in glomerular filtration and cumulative incidence of ESRD.  Kaplan-Meier survival curves compared by log rank test.  Cox regression used in analysis of predictors of ESRD or death.  Multiple regression analysis also performed.  Paired and unpaired t tests used to compare results within or between the 2 diet groups.

 

Data Collection Summary:

Timing of Measurements - every 3 months for 4 years or until death or withdrawal

Dependent Variables

  • Glomerular filtration rate - 51Cr-EDTA or Cockroft-Gault equation
  • End stage renal disease (dialysis initiated)
  • Death

Independent Variables

  • Dietary protein intake assignment

Control Variables

  • medication use
  • weight
  • urinary albumin
  • urinary urea
  • urinary sodium
  • serum albumin
  • serum urea
  • hemoglobin
  • hemoglobin A1C
  • blood pressure
  • serum total cholesterol, HDL cholesterol, triglycerides
  • serum calcium and phosphorus
  • anthropometric measurements
  • nutritional status
  • smoking habits

 

Description of Actual Data Sample:

Initial N: 82 (29 F, 53 M)

Attrition (final N): 82, none of the patients were lost to follow-up.

Age: 40 + 9 y

Ethnicity: not mentioned

Other relevant demographics: BMI 25 + 4

Anthropometrics - groups matched at baseline on all measures

Location: Steno Diabetes Center, Gentofte, Denmark

 

Summary of Results:

 

Variables

Usual Protein Group (n=34)

 

Low Protein Group (n=38)

 

Follow-Up Years - Before 5.1 years 5.0 years
Follow-Up Years - During 

4.0 years

4.0 years

Rate of Decline in GFR - Before 6.6 ml/min/year 7.6 ml/min/year
Rate of Decline in GFR - During 3.9 ml/min/year, P < 0.005 3.8 ml/min/year, P < 0.005
Albuminuria - Before 721 mg/24 hr 690 mg/24 hr
Albuminuria - During 614 mg/24 hr 542 mg/24 hr
SBP - Before 138 mm Hg 140 mm Hg
SBP - During 140 mm Hg 142 mm Hg
DBP - Before 85 mm Hg 85 mm Hg
DBP - During 79 mm Hg, P < 0.001 80 mm Hg, P < 0.001
HbA1c - Before 9.6% 9.8%
HbA1c - During 9.6% 9.5%, P < 0.05

Other Findings

After randomization and within the first 3 months there was an initial decline in the dietary protein intake of 0.06 g/kg/day (P = 0.24) in the usual protein group and 0.15 g/kg/day (P = 0.01) in the low-protein diet group.

After 3 months and during the follow-up period, the usual protein group consumed 1.02 g/kg/day (95% CI: 0.95 to 1.10) as compared with 0.89 g/kg/day (95% CI: 0.83 to 0.95) in the low protein group (P = 0.005).

The mean decline in GFR was 3.9 mL/min/year (95% CI: 2.7 to 5.2) in the usual protein diet group and 3.8 (95% CI:  2.8 to 4.8) in the low protein diet group.  The average improvement of the rate of decline in GFR, comparing slopes before and after randomization, were comparable in the 2 diet groups.

The relative risk of ESRD or death was 0.23 (0.07 to 0.72) for patients assigned to a low-protein diet, after an adjustment at baseline for the presence of cardiovascular disease (P = 0.01).

HbA1c and blood pressure values were comparable during follow-up in the 2 diet groups.  Rate of decline in GFR correlated with increase in mean blood pressure, hemoglobin A1c and albuminuria.

 

Author Conclusion:
In conclusion, moderate dietary protein restriction improves prognosis in type 1 diabetic patients with progressive diabetic nephropathy in addition to the beneficial effect of antihypertensive treatment.  Our study suggests that a wider use of dietary protein restriction is indicated in these patients.
Funding Source:
Not-for-profit
1
Foundation associated with industry:
Reviewer Comments:
Conclusions confounded by the usual protein group also reducing their protein intake, so dietary protein was not very different.  The positive effect of dietary protein restriction supported by the observation that both groups reduced their rate of decline of GFR when included in the study. 
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? N/A
  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? Yes
  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? Yes
  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? Yes
  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.) Yes
  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? ???
  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)? Yes
  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? N/A
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