CKD: MNT (2010)
The purpose of this study was to determine the effect of protein restriction on the course of albuminuria in patients with type 2 diabetes during a period of 12 months.
1. Detectable albuminuria or
a. microalbuminuria: 30-300 mg/24 hr (mean of 2 samples)
b. albuminuria: >20 mg/24 hr in 1 sample c. >6.5 mg/L in 2 samples
2. Duration of diabetes: >5 yr
3. <79 yr of age
1. Recovering from severe morbidity
2. Protein losing enteropathy
3. Venous leg ulcer
4. Pressure ulcer
5. Malignancy
6. Psychiatric or serious psychosocial problems
7. Baseline protein intake <0.8 g/kg/d
8. Low compliance to keeping appointments
9. Reluctant or unable to follow a restricted diet.
10. Positive for urinary tract infection at the time urine samples were taken for albumin.
Recruitment:
Forty six general practitioners selected all patients meeting 1985 WHO criteria for type 2 diabetes; 204 subjects met the study criteria.
Design: Randomized controlled Trial
Blinding Used (if applicable): Physician blinded.
Intervention (if applicable):
1. Random assignment to control or experimental (protein restricted to 0.8 g/kg/d) diet with stratification for use of ACE inhibitors.
2. All subjects received individual nutrition counseling from a dietitian to restrict saturated fat at months 1 and 3 and q 3 months thereafter for ~30 minutes per session. The experimental group also received instruction on a protein restricted diet.
3. Biochemical data:
a. albuminuria: estimated from duplicate 24-hr urine samples at 0, 6 and 12 months.
b. dietary protein intake: estimated from 24-hr urinary urea excretion + FFQ at 0, 6 and 12 months.
c. creatinine clearance (serum and urine creatinine) at 0, 6 and 12 months.
Statistical Analysis:
Differences between the two groups were subjected to a two-sided t-test; a natural logarithm was used for variables that were not distrubuted normally. Differences in categorical variables were subjected to a chi square test. Intention to treat analysis was applied by comparing differences in natural logarithm (albuminuria) during follow-up between study groups. Linear regression analysis was applied, with adjustment for albuminuria at baseline.
Timing of Measurements:
Twenty-four hour urine samples were obtained during a qualification period. Shortly before randomization another 24-h sample was collected, and the following morning non-fasting venous blood samples were obtained. After 6 and 12 months, duplicate 24-h urine samples were collected on non-consecutive days, and non-fasting venous blood sample were again obtained.
Dependent Variables:
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Albuminuria (mg/24-hr)
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Creatinine clearance
Independent Variables:
- Dietary protein intake < 0.8 g/kg/day
Control Variables
Initial N: 204 patients met study criteria. Informed consent given by 160 patients.
Attrition: 121; The control group had two patients die during the study, four with incident comorbidity, nine had patient-related logistic problems, 22 had microalbuminuria (30-300mg 24h), and one had no leucocyturia and no nitrite-positive urine in combination with albuminuria >/= 20mg 24h. The experimental group had five with incident comorbidity, four patients had problems with the diet, 11 had patient-related logistic problems, 17 had microalbuminuria (30-300mg 24h), and three had no leucocyturia and no nitrite-positive urine in combination with albuminuria >/= 20mg 24h.
Age: Experimental group- 64 +/-8, Control group- 63 +/-8
Ethnicity: four patients were non-Caucasian.
Other relevant demographics and anthropometrics:
Baseline Characteristics of 121 type 2 diabetic patients
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protein-restricted n=58
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control n=63
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Age, yr
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64+8
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63+8
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Duration of Diabetes, yr
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6.8+4.2
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7.2+4.8
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Male, %
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67.4
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55.5
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BMI
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27.3+4.2
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28.1+4.9
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HbA1c, %
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7.6+1.3
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7.7+1.4
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Location: The Netherlands
Microalbuminuria: At 6 and 12 months, respectively, albuminuria was 28% (P<0.001) and 18% (P=0.08) lower in the protein restricted group compared to the control group.
Dose-response analysis showed that a 0.10 g/kg change in protein intake (particularly animal protein) (decrease) in 6 months was related to an 11.1% change (decrease) in albuminuria (P<0.005), combining intakes at 6 and 12 months, suggested a change of 9.1%.
After 6 months, protein intake was significantly decreased in the protein restricted group (-0.05+0.21 and +0.03+0.019 g/kg) (P<0.02) by urinary urea determinations. However, the differences at 12 months were not significantly different by group (-0.05+0.27 vs. –0.01+0.22 for protein restricted and control groups, respectively.
Data on the intervention period of 121 type 2 diabetic patients
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Protein-restricted (n =58)
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Control (n =63)
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6 months
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12 months
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6 months
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12 months
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Body weight (kg)
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81 +/-14
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81 +/-14
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83 +/-14
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82 +/-14
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Serum Creatinine (µmol/l)
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106 +/-18
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106 +/-21
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99 +/-23
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99 +/-22
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Creatinine Clearance (ml/min/1.73m2)
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79 +/-21
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79 +/-17
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84 +/-23
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84 +/-22
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Total protein intake (g/kg),urea
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1.11 +/-.20
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1.12 +/-23
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1.19 +/-.30
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1.15 +/-.30
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Albuminuria (mg/24h, decrease in %)
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18.5 (8,36)
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19.6 (8,46)
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23.7 (9,65)
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22.2 (8,48)
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The findings of this study support the hypothesis that protein restriction in persons with type 2 diabetes in primary care can improve intermediate end-point albuminuria in both normo- and microalbuminuric patients. However, the majority of patients were not able to reduce dietary protein intake.
Future studies should address the long-term feasibility and efficacy of a diet with greater amounts of plant than animal protein on albuminuria and GFR.
Not-for-profit |
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The study demonstrates that lowering dietary protein intake an average of 0.05 g/kg/d (1.1 g/kg/d vs. 1.2 g/kg/d) can influence albuminuria.
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.) | ??? | |
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? | Yes | |
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? | 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? | No | |
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? | Yes | |
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 | |