EAL

CKD: MNT (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the effect of a very-low-protein diet supplemented with amino acids and ketoanalogues on the course of nutritional status and body composition in patients with advanced chronic renal failure (mean GRF=15+4.7mL per minute/1.73m²) during two years of follow-up.

Inclusion Criteria:

CKD with mean GFR of 15+4.7mL per minute/1.73m² and average age 55.

Exclusion Criteria:

Patients with severe comorbid conditions that might be superimposed by a hypercatabolic state; patients who could not adapt to the dietary prescription or to close monitoring.

Description of Study Protocol:

Recruitment

Patients recruited from the ambulatory.

Design

Time series study for two years; patients were prescribed on a very-low-protein diet supplemented with amino acids or keto analogues (SVLPD) that provided 0.3 grams per kilogram per day of vegetal protein and one tablet for every 5kg of body weight per day mixture of essential amino acids and ketoanalogues. All patients received 35 kilocalories per kilograms per day (carbohydrates: 67%, fats: 30% and protein: 3%). Patients with proteinuria greater than 3 grams per 24 hours, 1 gram of high biologic protein was added for each gram lost in the urine. All patients met once per month with a dietitian for diet compliance and efficacy of the dietary prescription. Compliance with the prescribed diet was assessed by interview after a four-day food diary during the first year but not for the second year. At the second year only compliance with protein intake was assessed. All patients received calcium carbonate supplement, iron tablets and water-soluble vitamins.

Intervention

Very-low-protein diet supplemented with a mixture of amino acids and keto analogues (SVLPD): 0.3 grams per kilogram per day plus one tablet of a mixture of calcium salts of essential amino acids and keto- analogues for each 5kg of body weight per day providing 36mg of nitrogen and 50mg of calcium.

Statistical Analysis

ANOVA for repeated measures to compare body composition data at different times, then a paired T-test was used to compare two time points for LBM and biologic values at T0, T12 and T24 months. Data are expressed as mean±1SD.

Data Collection Summary:

Timing of Measurements

Compliance with the diet was assessed each three months at the first year but discontinued during the second year. Protein intake was assessed monthly. Anthropometric and biochemical measurements were taken monthly, and every three months plasma parathyroid hormone and GFR.

Dependent Variables

Total protein
Transferrin
Albumin
Prealbumin
Serum urea and creatinine
Urine creatinine and urea
Proteinuria
GFR (mL per minute/1.73m²)
Body composition-using DEXA
BMI (Kg/m²)
Weight (Kg).

Independent Variables

SVLPD

Control Variables

Protein intake (grams per kilogram per day)
Age
Gender.

Description of Actual Data Sample:

Initial N

13 (eight male, five female)

Attrition (final N)

13 (eight male, five female)

Age

Mean age: 55; range: 39 to 70 years

Ethnicity

Not mentioned

Other relevant demographics

At baseline there was more males (61%) than females. The underlying diagnoses included chronic glomerulonephritis (five), chronic interstitital nephritis (two), vascular sclerosis (two), polycystic kidney disease (two), unknown cause (two). At baseline patients were either on stage four or five CKD, therefore, differing in the level of renal damage.

Anthropometrics

At baseline patients presented normal BMI

Location

Hopital Pellegrin, Bordeaux, France

Summary of Results:

Variables	Time 0 months	Time 12 months	Time 24 months
Dietary protein intake(grams per kilogram per day)	0.8±0.3	0.39±0.15	0.4±0.1*
Plasma urea (mmol/L)	19±5.7	6.8±3.4	8.6±4.9*
Plasma creatinine (µmol/L)	346±57	358±85	417±137*
GFR (mL per minute)	15±4.7	14.4±6.1	12.4±5.6
Parathyroid hormone (ng/mL)	206±124	108±24	80±50*
Weight (Kg)	67±16	66±15	68±14
BMI (Kg/m²)	23.2±3.7	23.3±4.1	24.1±3.4
Albumin (g/L)	40.2±6.5	40.3±4.6	38.9±3.3
Prealbumin (g/L)	0.40±0.09	0.43±0.08	0.38±0.08
Transferrin (g/L)	1.91±0.4	1.9±0.4	1.9±0.4

*P<0.05, Time 24 vs. Time zero

Other Findings

Calorie intake in the first year: Mean intake was 30±8 and 31±9 at Time zero and Time12 months, respectively.
Body composition: No significant change occurred in total fat mass or percentage of fat mass between Time zero and Time 24 months. There was a significantly decrease in the lean body mass (LBM) in the first three months; P<0.03, however a significant increase occurred after three months and exceeded baseline levels at the end of the study; P<0.027. Total bone mass and lumbar or hip site bone significantly decreased from Time zero to Time 12 and Time 24 months; P<0.05. Total bone mass linearly decreased around 2.85% in the first year and 5.6% in the second year.

Author Conclusion:

This study confirms that in carefully selected patients SVLPD is nutritionally safe for long periods, but attention must be paid to bone loss. The initial decrease in LBM corresponds to the physiologic adaptation to the reduced protein intake and is followed by a slight and progressive increase in LBM.

Funding Source:

University/Hospital:

Hopital Pellegrin, Hopital du Haut-Leveque

Reviewer Comments:

Overall the study is not very well designed and has a lot of limitations. One of the main limitations was the type of population studied. Patients were carefully selected, motivated, and monitored regularly, therefore, differing from the overall pre-dialysis population. The small sample size can increase type two error. Compliance to the diet in the second year was jeopardized by the lack of continuity with the food-diaries from most of the patients. Finally, sample population in this study seems to be the same used in the study published before (1999).

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?	???
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?	N/A
	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?	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?		???
	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%.)	N/A
	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?	???
	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?	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?	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?	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)?	No
	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?		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