CKD: Energy Requirements (2001)


Bernhard J, Beaufrere B, Laville M, Fouque D. Adaptive response to a low-protein diet in predialysis chronic renal failure patients.  J Am Soc Nephrol. 2001;12:1249-1254.


Worksheet created prior to Spring 2004 using earlier ADA research analysis template.
PubMed ID: 11373349
Study Design:
Randomized controlled trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

The purpose of this study was to determine the effects on nitrogen metabolism of a low protein diet and a low protein diet supplemented with ketoanalogs of amino acids. 

Inclusion Criteria:

Protein intake between 1 and 1.5 g/kg/d and energy intake >30 kcal/kg based 3-day diet record and 24-hr urine for urea determinations.

Exclusion Criteria:
  • Subjects willing to lose weight.

  • Diabetic

  • Malignant or inflammatory illness

Description of Study Protocol:


Patients from renal diet clinic.

Design:  Randomized Controlled Trial.

1. All subjects received conservative treatment including calcium carbonate, vitamin D supplementation, sodium bicarbonate and antihypertensives if needed.

2. The renal dietitian interviewed each subject twice before study inclusion.

    a. subjects were referred for the study soon after renal disease was diagnosed.

    b. subjects consumed usual diet for 4 to 6 weeks before randomization to the study diet.

3. Metabolic study:

    a. subjects were admitted to a metabolic unit for 4 days for baseline studies of leucine turnover.

    b. leucine turnover study was carried out on the 4th day of admission to the metabolic unit.

        1) after fasting from 8 pm the previous evening, subjects received L[1-13C] leucine by IV at 0.08 µmol/kg/min over the next 3.5 hr

        2) 4 times during the last hour blood and gas samples were taken and CO2 production rate measured by indirect calorimetry. 

    c. blood was drawn for amino acid determinations at 7:45 a.m. on the 4th day of the metabolic study after an overnight fast.

Blinding Used (if applicable):

Blinding not used - lab tests.


Subjects were randomly assigned to low protein diet (0.6 g/kg/d) with ~50% of protein being high biological value or the same low protein diet supplemented with ketoanalogs of amino acids; energy intake was kept constant at 31 kcal/kg/d over the 3 month period.

Statistical analysis 

Paired t baseline versus admission values; Wilcoxon test between time points of dietary intervention

Data Collection Summary:

Timing of measurements

Subjects were seen monthly for 3 months

Dependent variables

  • Endogenous leucine flux
  • Amino acid oxidation
  • Nonoxidative leucine disposal.

Independent variables

  • Low protein diet
  • Ketoacid supplement
  • Compliance to study diet was evaluated by monthly 3-day food records and a 24-hr urine collection for urea determination.

Control Variables

Description of Actual Data Sample:

Initial N: 12 subjects with CRF, 10 men, 2 women

Attrition (final N): 12, no attrition reported

Age:  mean 44.3+4.6 yr.

Ethnicity: not mentioned

Other relevant demographics:

Anthropometrics:  BMI normal

Location: Lyon, France

Summary of Results:

Characteristics after 3 month study:

LPD n=6

LPD + Keto acid n=6

Age, yr






Serum creatinine (µmol/L



Serum albumin (g/L)



Serum PTH (ng/L)



Serum phosphorus (mmol/L)



Proteinuria (g/d)



Compliance to low-protein diet:


Baseline 3 months

Energy intake (kcal/kg/d)



Protein intake (g/kg/d)



Urinary urea (mmol/d)



Protein nitrogen appearance (g/kg/d)



a = P<0.05 compared to baseline

(The dietary protein intake in the ketoanalogues was not included in the estimated protein intake and averaged 0.08+0.0004 g of protein/kg/d).

There was no difference in leucine oxidation values before and after a 3 month low protein diet with and without ketoacid supplementation.

The results of leucine turnover was pooled for the two study groups. The reduction in protein intake induced a decrease in leucine oxidation by ~18% (P<0.05), associated with a parallel 8% reduction (P<0.05) in leucine rate of appearance, an estimate of protein degradation. There was no change in nonoxidative leucine disposal during the low protein diet period.

Author Conclusion:

This is the first report of a 3-month moderate reduction in protein intake in patients with mild GFR that shows an adequate metabolic and body composition response. This suggests that with an energy intake >31 kcal/kg/d, a protein intake of 0.7 g/kg/d is metabolically and nutritionally safe. This study confirms the evidence for prescribing a low-protein diet to patients with mild CFR. Whether patients eventually will accept it certainly may rely more on physicians’ beliefs and enthusiasm.

Funding Source:
Government: INSERM
University/Hospital: Hospital Edouard Herriot, Laboratoire de Nutrition Humaine
Reviewer Comments:

Well-designed and controlled study that demonstrated that individuals with CRF adapt to a low protein diet by decreased utilization of amino acids for energy. The dietary protein restriction was 0.71 g/kg/d but intake by urine urea was closer to 0.8 g/kg/d until the third month.

The lack of difference in KA supplementation and no supplementation is probably due to small sample size.  KA effects on protein metabolism were all less negative than without KA.  No discussion of whether these could be clinically significant.

The renal dietitian interviewed the patients monthly for counseling and to evaluate dietary compliance.

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? 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? 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? Yes
  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? ???
  8.1. Were statistical analyses adequately described and the results reported appropriately? No
  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)? N/A
  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? No
  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