Feiten SF, Draibe SA, Watanabe R, Duenhas MR, Baxmann AC, Nerbass FB, Cuppari L.  Short-term effects of a very-low-protein diet supplemented with ketoacids in nondialyzed chronic kidney disease patients.  Eur J Clin Nutr 2005;59:129-136. 

PubMed ID: 15354199
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

Compare the effects of a very low protein diet supplemented with keto acids with a low protein diet on nutritional and metabolic parameters in patients with advanced chronic kidney disease.

Inclusion Criteria:
  • creatinine clearance equal or less than 25 ml/min/1.73m2
  • older than 18 y
Exclusion Criteria:
  • absence of catabolic illnesses, diabetes mellitus, autoimmune disease and malignant hypertension
Description of Study Protocol:

Recruitment - clinic patients 

Design - randomized controlled clinical trial

Blinding used - none - lab tests

Intervention - reduced protein intake with or without ketoacid supplementation

Statistical Analysis - analysis of variance complemented with Bonferroni test for comparisons of anthropometric and dietary periods, Fisher's exact test used for comparisons between groups, paired Student's t test used to compare biochemical parameters at baseline and 4 months, independent Student's t test used to compare the two groups between two periods, Pearson's correlation coefficient to test associations between two variables


Data Collection Summary:

Timing of Measurements - baseline and monthly for 4 months

 Dependent Variables

  • fasting blood and urine samples analyzed for serum and urinary urea and phosphorus, serum creatinine, ionized calcium, bicarbonate, albumin and intact PTH
  • body weight and height, BMI
  • midarm circumference and triceps skinfold thickness 
  • body composition using bioimpedance analysis

Independent Variables

  • low protein diet was 0.6 g/kg/day protein, very-low-protein diet was 0.3 g/kg/day with ketoacid/amino acid supplement (1 tablet/5 kg IBW/day)
  • dietary energy and protein using 3 day food diaries 

Control Variables - not given


Description of Actual Data Sample:

Initial N: 24 (15 M, 9 F), 12 in each group

Attrition (final N): none; 24

Age: 49.7 + 11.3 (VLPD + KA); 43.9 + 16.3 (LPD)

Ethnicity: Brazilian

Other relevant demographics: one half normal weight, one-half overweight or obese at baseline

Anthropometrics - the groups were not different statistically on baseline measures, but the groups were small (12 each)

Location: Federal University of Sao Paulo, Brazil

Summary of Results:



Very Low Protein plus ketoacids

4 months

Low Protein

4 months

Statistical Significance of Group Difference

Dietary protein (g/kg/d)

0.43 + 0.12

0.69 + 0.18

not given
Change Creatinine clearance -0.83 + 3.5 -1.8 + 2.9 0.46
Change serum urea nitrogen -38 + 27.9 -10 + 27.2 0.02
Change dietary P -156 + 136 -11 + 113 0.01
Change serum P -0.65 + 1.1 -0.03 + 0.9 0.15
Intact PTH 60 + 319 303 + 294 0.10

 Other Findings - no change in nutritional status with either diet


Author Conclusion:

No deterioration in creatinine clearance or nutrititional status on either diet, with some improvement in calcium, phosphorus and PTH in the VLPD plus KA.

Funding Source:
University/Hospital: Federal University of Sao Paulo
Reviewer Comments:
The lack of differences in creatinine clearance and body composition may be due to the short length of the study and small numbers of patients, as negative trends were seen.  The investigators admit that dietary protein and energy were likely to have been under-recorded - very-low protein diet did not reach goal of 0.3 g/kg/day.
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? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  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? N/A
  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? ???
  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? No
  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? No
  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? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? ???
  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? No
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? No
  7.5. Was the measurement of effect at an appropriate level of precision? No
  7.6. Were other factors accounted for (measured) that could affect outcomes? ???
  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? ???
  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)? ???
  8.6. Was clinical significance as well as statistical significance reported? ???
  8.7. If negative findings, was a power calculation reported to address type 2 error? No
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