DM: Protein Amount (2014)
- 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
- pregnancy
- history of congestive heart failure, myocardial infarction or coronary bypass surgery within the last 3 months
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.
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
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
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.
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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? | 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 | |