CKD: MNT (2010)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:

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.

Inclusion Criteria:

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

Exclusion Criteria:

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.

Description of Study Protocol:

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.

 

Data Collection Summary:

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:

  • Albuminuria (mg/24-hr)
  • Creatinine clearance

Independent Variables:

  • Dietary protein intake < 0.8 g/kg/day

Control Variables

Description of Actual Data Sample:

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
 
protein-restricted n=58
control n=63
Age, yr
64+8
63+8
Duration of Diabetes, yr
6.8+4.2
7.2+4.8
Male, %
67.4
55.5
BMI
27.3+4.2
28.1+4.9
HbA1c, %
7.6+1.3
7.7+1.4

Location: The Netherlands

Summary of Results:

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
 
Protein-restricted (n =58)
Control (n =63)
 
6 months
12 months
6 months
12 months
Body weight (kg)
81 +/-14
81 +/-14
83 +/-14
82 +/-14
Serum Creatinine (µmol/l)
106 +/-18
106 +/-21
99 +/-23
99 +/-22
Creatinine Clearance (ml/min/1.73m2)
79 +/-21
79 +/-17
84 +/-23
84 +/-22
Total protein intake (g/kg),urea
1.11 +/-.20
1.12 +/-23
1.19 +/-.30
1.15 +/-.30
Albuminuria (mg/24h, decrease in %)
18.5 (8,36)
19.6 (8,46)
23.7 (9,65)
22.2 (8,48)

Author Conclusion:

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.

Funding Source:
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:

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
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