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CKD: Energy Requirements (2001)

Citation:

Maroni BJ, Staffeld C, Young VR, Manatunga A, Tom K. Mechanisms permitting nephrotic patients to achieve nitrogen equilibrium with a protein-restricted diet.  J Clin Invest. 1997; 10: 2479-2487.

Worksheet created prior to Spring 2004 using earlier ADA research analysis template.
PubMed ID: 9153292
 
Study Design:
Randomized Controlled Trial
Class:
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 metabolic responses to dietary protein restriction in patients with nephrotic syndrome.

Inclusion Criteria:

 5 subjects with nephritic syndrome;  5 subjects healthy subjects.

Exclusion Criteria:
  • Diabetes mellitus

  • Body weight <80% or >120% Standard Body Weight (SBW)

  • Taking medications that would affect protein metabolism

Description of Study Protocol:

Recruitment 

Clinic patients - methods not described.

Design:  Randomized Controlled Trial.

1. Before the initial CRC admission, a history and physical exam was performed and a chemistry panel, complete blood count, urinalysis, and 24-h urine protein obtained.

2. The research dietitian met with each subject to do anthropometric measurements and design the metabolic diet:

3. Metabolic study:

a. assignment to study diet was randomized.

b. prepackaged meals were provided to subjects for 14 d prior to metabolic studies to allow for equilibration.

c. following a 4-day lead-in period, a 5-d nitrogen balance study was conducted during each 10-day stay in the CRC.

d. days 2 & 9, complete blood count, chemistry panel and serum transferrin

e. blood urea nitrogen was obtained each morning

f. day 2, GFR was measured using [125I]-Iothalamate

g. day 3, 13CO2 was measured during an infusion of NaH13CO3.

h. day 10, leucine kinetics were measured during fasting and feeding

Blinding (if applicable): 

Blinding not used - lab tests.

Intervention (if applicable):

0.8 or 1.6 g protein and 35 kcal/kg SBW/d; patients with nephrotic syndrome received an additional 1 g protein/1 g urinary protein; b. phosphorus: < 12 or 24 mg/kg SBW/d; c. sodium: 2-4 g

Statistical analysis

Three way ANOVA to evaluate the impact of diet on leucine turnover and plasma amino acid concentration; two way ANOVA to compare N balance between nephrotic and healthy subjects; effect of sequence of treatments was tested.

Data Collection Summary:

Timing of measurements

14 d adaptation followed by 9 days in metabolic unit each diet

Dependent variables

  • Nitrogen balance
  • Whole body protein turnover
  • Plasma amino acid concentrations
  • Urinary protein

Independent variables

  • Dietary intervention

Control Variables

Description of Actual Data Sample:

Initial N: 10 subjects, 5 with nephrotic syndrome, 5 healthy controls

Attrition (final N):  10

Age: 37 to 72 years for those with nephrotic syndrome, 23 to 42 years for healthy controls

Ethnicity:  not given

Other relevant demographics and anthropometrics:

Characteristics of 5 subjects with nephrotic syndrome during metabolic studies.
 

Dietary Protein

 

0.8 g/kg

1.6 g/kg

Weight, kg

76.0±2.0

75.9±2.1

Kcal/kg/d

34.1±0.6

34.9±0.1

Protein, g/kg/d

1.00±0.03

1.85±0.04

Albumin (mg/dL)

2.3±0.4

2.2±0.04

Transferrin (mg/dL)

186±21

200±27

Urine protein (g/d)

6.8±1.9

8.2±2.4

GFR (ml/min)

49±12

54±18

Location - Emory University, Atlanta Georgia USA

Summary of Results:

Both the control subjects and those with nephrotic syndrome were in positive nitrogen balance while consuming the high protein diet +5.73 ±1.34 vs. + 2.05±0.46 g Nitrogen/d; P<0.05, nephrotic vs control, respectively. During the low protein diet, the subjects were in neutral or positive nitrogen balance, -0.33 to + 3.45 g nitrogen/d vs. +1.09 ± 0.40 nitrogen/d, P=NS, nephrotic vs. control respectively.

Leucine oxidation rates during feeding were significantly lower on the low protein diet compared to the highprotein diet in both control and subjects with nephrotic syndrome. (nephrotic: 23.4±2.6 vs. 39.2±3.9, control 27.4±1.5 vs. 45.9±6.3 µmol/kg/hr).

There was an inverse correlation between urinary protein losses and feeding leucine oxidation rates when nephrotic patients consumed the low protein diet (r=-0.83; P=0.04) suggesting that proteinuria is a stimulus to conserve dietary amino acids when dietary protein is restricted.

Author Conclusion:

A diet providing 0.8 g protein + 1 g protein/gram urinary protein and 35 kcal/kg/d maintains nitrogen balance in patients with nephrotic syndrome. Normal anabolic responses to dietary protein restriction are activated in patients with nephrotic syndrome—these anabolic responses are suppression of amino acid oxidation and stimulation of protein synthesis and inhibition of protein degradation.

The inverse correlation between leucine oxidation and urinary protein losses suggests that proteinuria is a stimulus to conserve dietary essential amino acids.

A limitation of this study is extrapolating short-term results (3 weeks) to long-term dietary adequacy. This study also, does not define the minimum protein requirement for patients with nephrotic syndrome or that supplementing protein intakes to replace urinary losses is necessary for nitrogen balance in these subjects.

Funding Source:
Government: NIH
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:

This study was able to demonstrate that leucine oxidation is decreased with protein intakes ~0.8 g/kg/d compared to 1.6 g/kg/d in both controls and individuals with nephotic syndrome. This suggests a mechanism to preserve dietary protein intake for nitrogen use instead of using leucine as an energy source. 

Negative significance on some outcome variables may be due to small numbers of subjects rather than lack of clinically significant differences (urinary protein loss?).

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? Yes
  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? Yes
  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? No
  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? N/A
  7.7. Were the measurements conducted consistently across groups? N/A
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)? 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