EAL

CKD: Energy Requirements (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to determine whether dietary protein restriction might induce potentially advantageous changes in albumin and fibrinogen metabolism in patients with nephrotic syndrome.

Inclusion Criteria:

Diagnosis of nephrotic syndrome.
20 to 50 years of age.
Urinary protein excretion >3.5 g/24-hr
No evidence of endocrine or other major organ system disease.
Control subjects: healthy

Exclusion Criteria:

1. Medical history, physical exam, and routine labs to rule out endocrine disease or other major organ system disease.

2. Renal biopsy to determine cause of nephrotic disease.

Description of Study Protocol:

Recruitment

Methods not specified.

Design: Randomized Crossover Trial.

1. Diet protocol: a. control subjects followed normal protein diet for >7 days prior to participation in the low protein diet.

b. subjects with nephrotic syndrome were randomly assigned to the normal protein or low protein diet and followed each for ~27 days.

1) normal protein diet (NPD): weight maintenance diet providing 35 to 38 kcal/kg/d, 250 to 300 g carbohydrate and 1.1 g protein/kg/d.

2) low protein diet (LDP): 35 to 38 kcal/kg/d and 0.55 g protein/kg/d + 1 g protein for each gram of urinary protein/d.

4. Metabolic studies after each 4 wk period of diet intervention after 12-hr overnight fast.

a. 24-hr urine collection for urinary protein.

b. leucine infusion (1.2 mg/kg/hr) of 5,5,5-D3-L-leucine over 5 hr.

c. 10 ml blood collected at –15, 0, 180, 210, 240, 270 and 300 minutes to measure the plasma concentration and enrichment of leucine, a-ketoisocaprioc acid and the enrichment of De-leucine bound to plasma albumin and fibrinogen.

d. plasma volume determined by Evans blue dye dilution method.

e. calculation of whole body leucine flux and albumin and fibrinogen fractional synthesis rate and absolute synthesis rate.

Blinding Used (if applicable):

Blinding not used - lab tests.

Intervention (if applicable):

Metabolic analysis performed after each 4-wek dietary period, which were started in random order and completed by all patients.

Statistical analysis:

Analysis of variance - intergroup comparisons. Comparison of dietary treatments - student t test for paired data. Correlations used not given.

Data Collection Summary:

Timing of Measurements

Weekly monitoring - each diet followed for 27 days.

Dependent Variables

Endogenous leucine flux (ELF)
Fractional synthesis rate
Absolute synthesis rate of albumin and fibrinogen
Blood levels of albumin and fibrinogen

Independent Variables

Normal protein or low protein diet
Weekly monitoring of diet compliance was done by having each subject come to the clinical unit with diet diary and a 24-hr urine specimen for urinary protein and nitrogen excretion determinations.

Description of Actual Data Sample:

Initial N: 7 healthy control subjects (4 male, 3 female) and 7 subjects with nephrotic syndrome (4 male, 3 female)

Attrition (final N): 7 controls, 7 subjects with nephrotic syndrome

Age: controls: mean age 37 +/- 3 years, subjects: mean age 39 +/- 3 years

Ethnicity: not mentioned

Other relevant demographics:

Anthropometrics:

Causes of nephrotic syndrome:
Membranoproliferative
Glomerulonephritis	3
Membranous nephropathy	2
Amyloidosis	1
Focal segmental
Glomerulosclerosis	1

Location: Italy

Summary of Results:

Characteristics after 4 wk study:
	NPD	LPD
Protein intake, (g/kg/d)	1.20+0.06	0.66+0.04a
BMI	24.7+2	24.2+2
Creatinine Cl (ml/min)	87+14	86+12
Proteinuria(g/d)	10.2+1.8	6.5+1.2a
Oxidation of Substrates (mg/kg/min) Carbohydrate	1.06+0.1	1.23+0.1
Lipid	0.78+0.05	0.81+0.06
Protein	0.71+0.04	0.39+0.03a
BEE (kcal/kg/d)	21.2+0.9	19.4+0.8a

a = P<0.03 LPD vs. NPD

In NS patients during the low protein diet period compared to the normal protein diet, endogenous leucine flux and albumin and fibrinogen synthesis rates decreased. Plasma albumin increased and plasma fibrinogen decreased. Dietary-induced changes in albumin and fibrinogen synthesis were significantly correlated (r=0.719, P<0.05).

Author Conclusion:

A protein restricted diet providing ~0.6 g/kg of protein (+1 g protein/ g of proteinuria) can induce significant improvements with an increase in serum albumin levels and the intravascular albumin pool, and a decreased plasma fibrinogen concentration and intravascular fibrinogen pool.

Funding Source:

University/Hospital:

University of Catania, University of Perugia, Second University of Napels

Reviewer Comments:

The results of this study are impressive. Subjects with nephrotic syndrome followed a diet containing 0.66 g protein/kg/d + 1 g for each g of proteinuria or ~44 g + 6.5 g or a total of 50.5 g protein/d. This level of protein restriction is more likely to be achieved by patients than greater restriction.

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?	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?	Yes
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.)	N/A
	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?	N/A
	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?		Yes
	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)?	N/A
	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