Citation:

Chauveau P, Barthe N, Rigalleau V, Ozenne S, Castaing F, Delclaux C, De Precigout V, Combe C, Aparaicio M. Outcome of nutritional status and body composition of uremic patients on a very low protein diet. Am J Kidney Dis. 1999; 34 (3): 500-507.

PubMed ID: 10469861
 
Study Design:
Time Study
Class:
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To study the outcome of a very-low-protein diet on the course of nutritional status and body composition in patients with advanced chronic renal disease during 12 months.

Inclusion Criteria:

Chronic kidney disease (CKD) with mean GFR of 13.2+4.8mL per minute per 1.73m2 and age range between 39 to 70 years.

Exclusion Criteria:

Not mentioned.

Description of Study Protocol:

Recruitment

Patients recruited from the ambulatory.

Design

Time-series for one year. Patients were prescribed on a very-low-protein diet supplemented with a mix of salts of essential amino acids and ketoanalogues in tablet form. The caloric content was 35kcal per kg per day, providing 67% of carbohydrates, 30% of fats and 3% of protein. Once a month, the patients met a dietitian and a physician for verification of compliance, safety and efficacy of the dietary prescription. Compliance was assessed by interview after a four-day period of food diary at three-month intervals, and it was also assessed by monthly measurements of urinary urea and phosphorus excretion. Patients with proteinuria greater than 3g per 24 hours, 1g of high biological protein was replaced for each gram lost in the urine. All patients received calcium carbonate, iron tablets and water-soluble vitamins. 

Intervention

Very-low-protein diet with 0.3g per kg per day of vegetable origin plus one tablet for 5kg of body weight of a mixture of calcium salts of essential amino acids and ketoanalogues, providing 36mg of nitrogen and 50mg of calcium.

Statistical Analysis

Analysis of variance for repeated measures was used to compared data at different times. Correlation and regression analysis. Data are expressed as mean±one SD.

 

Data Collection Summary:

Timing of Measurements

Compliance of the diet was assessed every three months. Urinary urea and phosphorus excretion were measured monthly. Anthropometric and biochemical measurements were also taken monthly but GRF was assessed every three months. Body composition was measured every three months.

Dependent Variables

  • BMI (kg/m2)
  • Weight (kg)
  • Body composition (lean body mass, limb/trunk lean ratio, total fat mass, fat mass) DEXA
  • Transferrin
  • Albumin
  • Pre-albumin
  • RBP
  • Serum creatinine 
  • Urea
  • Urinary creatinine, 24 hours
  • GFR (mL per minute per 1.73m2), urinary clearance of  51Cr EDTA.

Independent Variables

Very-low-protein diet supplemented with a mixture of amino acids and ketoanalogues.

Control Variables

  • Protein intake (g per kg per day)
  • Age
  • Gender.
Description of Actual Data Sample:
  • Initial N: 10 (six male, four female)
  • Attrition (final N): 10 (six male, four female)
  • Age: Mean 57 years; range from 39 years to 70 years of age 
  • Other relevant demographics: The underlying diagnosis included chronic glomerulonephritis (five), chronic interstitial nephritis (two), vascular sclerosis (two) unknown cause (one)
  • Anthropometrics: At baseline the body weight, total body fat and lean body mass was less in the patient group but their BMI was normal
  • Location: Pellegrin-Tripode Hospital, Bordeaux Cedex, France.
Summary of Results:
  • Outcome of biochemical and anthropometric indicators of nutritional status in CKD patients: There was no statistical difference in all nutritional markers at the end of the study.

Variables

Time: Zero

Time: 12 Months

BMI (kg/m 2)

24.6±2.9

24.7±3.3

Weight (kg)

69±13.6

69.1±12.6

TSF (mm)

14.5±7.3

15.7±8.1

AMC (cm)

30.9±2.1

31.1±2.4

Albumin (g per dL)

40.7±7.4

40.5±4.7

Pre-albumin(g per L)

0.39±0.08

0.44±0.06

Transferrin (g per L)

2.16±0.5

2.02±0.4

GFR (ml per minute per 1.73m 2)

13.2±4.8

12.1±6.6

Creatinine (mg per L)

44.1±11.1

48.4±14.5

  • NS: Not significant 
  • Alimentary intake: Dietary protein intake in CKD patients was reduced significantly at the end of the third month (0.78±0.23g to 0.28±0.05g per kg per day; P<0.0001) and remained the same during the rest of the study: 0.29+0.05g per kg per day at one year
    • Energy intake was slightly increased from 27.8±7.6kcal to 31.0±8.1kcal per kg per day at the end of the third month and stabilized at 29.8+8.8kcal per kg per day at one year
    • Urinary creatinine excretion decreased in the first month (1.03+0.24g to 0.89+0.19g per 24 hours; P<0.05) and was maintained in 0.85±0.18g per 24 hours at the end of the study.
  • Body composition: 

Time

Time: Zero

Time: Three

 Time: Six

Time: 12

Total body fat (%)

29.2+8.7

31.6+8.3*

31.6+8.4**

31.2+8.8

Fat Mass (g)

20.1+6.9

21.3+6.7&

21.4+6.7

21.4+7.1

Lean body mass (kg)

46.2+10.2

43.9+9.7#

44.5+9.5##

45.1+9.8

Limb to Trunk lean ratio

 0.87+0.12

0.84+0.13 

0.84+0.13 

 0.83+0.11&

*P=0.003; **P=0.015; & P=0.021; #P=0.03; ##P=0.002; all vs. Time: zero. 

Other Findings

  • Physical activity remained unchanged in all patients; all remained clinically stable during the first year of survey
  • Urinary protein excretion was decreased during the study; P<0.001.

 

Author Conclusion:

Patients with advanced chronic kidney disease consuming very-low-protein diet supplemented with a mixture of amino acids and ketoanalogues can maintain nutritional status during long-term management, with stable body weight and conventional nutritional markers. However, changes in body composition can occur, such as increased fat mass and decreased lean fat mass in the first three months. These mild changes do not appear to be deleterious given the favorable long-term outcome of these patients, even after they began dialysis treatment or renal transplantation.

Funding Source:
Reviewer Comments:

Patients were nutritionally stable, differing from the overall pre-dialysis population with advanced chronic kidney disease. Very small sample size can increase the risk of type two error. Exclusion criteria were not mentioned, which makes the sample population less representative due to the possible tendency to choose those without malnutrition.

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) ???
  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) ???
 
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? No
  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? No
  2.2. Were criteria applied equally to all study groups? ???
  2.3. Were health, demographics, and other characteristics of subjects described? No
  2.4. Were the subjects/patients a representative sample of the relevant population? No
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) No
  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%.) No
  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? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? ???
  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? 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? 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? ???
  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? ???
  7.6. Were other factors accounted for (measured) that could affect outcomes? No
  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)? No
  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? No
9. Are conclusions supported by results with biases and limitations taken into consideration? No
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
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