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CKD: Nutrition Status Parameters (2010)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

The purpose of this study was to evaluate the relationship between parameters of nutritional status and GFR in subjects being screened for participation in the Modification of Diet in Renal Disease Study (MDRDS) at baseline.
Inclusion Criteria:
Methods cited elsewhere, but including stable subjects with moderate to advanced CRI.
Exclusion Criteria:

Methods cited elsewhere, but excluding subjects with inflammatory or catabolic diseases, IDDM, nephrotic syndrome, frank malnutrition.

Description of Study Protocol:

Recruitment:  Methods cited elsewhere

Design:  Cross-sectional

Blinding used:  not applicable

Intervention:  not applicable

Statistical analysis:

  • Men and women analyzed separately. Different sample sizes were used for analyses of different variables, then assessed for robustness using subset of n=988 with complete data for all variables.  Results from this subset were similar to those obtained using all available data.
  • Two-sided P values to assess level of significance, determined by P<0.05.
  • GFR standardized to body surface area.
  • Protein and energy intakes factored by standard body weight.

Initial descriptive analyses:

Subjects divided into 3 groups according to GFR, allowing for sufficient sample size in each subgroup:

  1. GFR <21
  2. GFR 21-37
  3. GFR >37

Two-sample t-tests and ANCOVA when comparing mean levels of nutritional variables with various subject subgroups.

Relationship of GFR with nutritional parameters:

Nonparametric regression with cubic smoothing splines for each nutritional parameter as a function of baseline GFR.

Joint relationship of nutritional parameters with GFR and protein/energy intakes:

Multiple regression analyses to investigate independent contribution of GFR, protein intake, and energy intake to nutritional parameters; controlled for age.  Bias controlled using n=738 with repeated (baseline) measures.

Data Collection Summary:

Timing of measurements: All measurements obtained within 2 weeks of baseline enrollment except anthropometric measures, which were obtained at the second month of baseline.

Dietitians were trained, then tested and certified for accuracy in data collection.

  1. GFR: measured using 125I-iothalamate clearance, factored by body surface area (BSA) for analyses.
  2. Nutrient intake: a) dietary protein and energy intakes were calculated from diet diaries by dietitians trained to use the University of Pittsburgh Nutrient Database. b) dietary protein was also estimated from urea nitrogen appearance (UNA) from 24-hr urine collections using the following formula: protein intake (g/d) = 6.25 [UUN (g/d) + 0.31 (g/kg/d) x standard body weight (kg).
  3. Biochemical: serum albumin, cholesterol, transferrin, serum and urine creatinine
  4. Anthropometrics: weight, height, BMI, arm muscle area, skinfold thickness at biceps, triceps, and subscapular

Dependent variables:

  • Nutritional parameters

Independent variables:

  • GFR
  • Gender
  • Attempt to restrict protein and/or energy intake

Control variables:

  • GFR, age and race when comparing with and without diet restrictions
  • GFR, age and diet restrictions when comparing nutritional variables with race (black vs non-black), and when comparing nutritional parameters as function of baseline GFR
Description of Actual Data Sample:

Initial N:

  • N=1785
  • 988 with complete data for all variables
  • 738 with repeat measurements at end of baseline period (3 months after initial assessment), used to control for bias in nutritional parameters analyses

Attrition (Final N):  not applicable

Age:

  • 50.4+12.8 (range 19-71) years
  • Men  (60%) 51.2+12.9 years
  • Women  (40%) 49.2+12.6 years

Ethnicity:

  • 80% white
  • 13% black
  • 5% Hispanic
  • 1% Asian
  • 1% other

Other relevant demographics:

  • 6% NIDDM
  • average GFR: 39.8+21.1 mL/min/1.73 m2
  • average dietary protein: 0.99+0.24 g/kg/day (per UNA), 1.01+0.33 g/kg/day (per diet records)
  • average energy intake (per diet records): 28.5+9.2 kcal/kg/day
  • 60.6% total subjects total cholesterol >200 mg/dL
  • 45.9% total subjects >110% SBW

Anthropometrics:

  • Weight, height, skeletal frame size (assessed by elbow width), MAMC, biceps, triceps, and subscapular skinfold thickness.
  • BMI, arm muscle area (AMA, using MAMC and TSF), percentge body fat (estimated from wt, ht and skinfold thickness).
  • Standard body weight determined from NHANES I and II data.

Location:  15 clinical centers throughout the United States.

Summary of Results:

Nutritional parameters by GFR and sex:

Men

 GFR
 

<21

>37

Age, yr

51.3±13.2

51.0±12.4

BMI

26.4±3.71

28.1±4.11

Serum creatinine (mg/dL)

4.35±1.14

1.59±0.34

Serum cholesterol (mg/dL)

204±47.4

216±49.9

Protein intake (g/kg/d), per UNA

0.88±0.19

1.06±0.30

Protein (g/kg/d), per food diary

0.90±0.27

1.13±0.35

Kcal/kg/day, per food diary

26.4±6.90

31.0±9.30

Serum albumin (g/dL)

3.99±0.40

4.10±0.39

Serum transferrin (mg/dL)

255±42.5

280±45.9

Arm muscle area (cm2)

42.3±11.6

48.1±11.3

Sum of skinfolds (mm)

34.1±11.5

40.8±13.8

Urine creatinine (mg/kg/d)

17.5±3.46

20.2±4.24
     

Women

    

Age, yr

50.8±12.6

47.7±12.5

BMI

26.0±5.27

26.8±5.36

Serum creatinine (mg/dL)

3.57±1.07

1.25±0.30

Serum cholesterol (mg/dL)

225±48.9

222±46.9

Protein intake (g/kg/d), per UNA

0.90±0.21

1.03±0.24

Protein (g/kg/d), per food diary

0.84±0.28

0.99±0.30

Kcal/kg/day

24.6±8.58

27.7±8.84

Serum albumin (g/dL)

3.88±0.36

4.06±0.32

Serum transferrin (mg/dL)

261±46.0

287±46.2

Arm muscle area (cm2)

28.1±15.9

29.6±12.6
Sum of skinfolds (mm)

45.1±17.4

53.7±17.5

Urine creatinine (mg/kg/d)

15.3±3.14

16.5±3.48

528/1785 attempted or had been advised to follow low protein diet, and had significantly lower protein intakes than those not attempting/advised (P<0.001), per diet records.  Per UNA, this association was weaker, but still significant in men (P<0.001; P=0.03 in women). 

Blacks differed from non-blacks on most nutritional parameters, particularly lower protein intake per UNA, higher urine creatinine, higher BMI, lower serum transferrin.

In men, GFR<21 was associated with statistically significant lower levels of all 16 diet parameters and nutritional measures.  GFR:21-37  associated with 11 parameters, (becoming nonsignificant for total cholesterol, % body fat, and skinfold indices).

In women, GFR<21 was associated with statistically significant lower levels of 11 parameters (protein intake per UNA, protein and energy per food records, albumin, transferrin, % body fat, skinfolds, and urine creatinine).  GFR:21-37 associated with lower levels in 10 of these 11 parameters (not energy intake) but not all statistically significant.

For men and women, a lower GFR was significantly associated with abnormally low albumin and transferrin, abnormally low total cholesterol for men only.  As GFR decreased from 60 to 10 ml/min:

  • serum albumin decreased from ~4.1 g/dL to 4.0 g/dL (men,P=0.004) and 3.85 (women, P<0.001)
  • serum transferrin decreased from ~280-290 mg/dL to ~255 mg/dL (P<0.001, men and women)

In multivariable regression analyses, the association between GFR with several of the anthropometric and biochemical nutritional parameters was either attenuated or eliminated completely after controlling for protein and energy intakes.  In men, lower GFR  remained significantly positively associated with % body fat and transferrin ; in women, transferrin and albumin.  However, when controlling for GFR, strong positive associations were seen between protein and energy intake and many of the other nutritional parameters measured.

A correlation matrix was created (n=988) for nutritional parameters, with some noteworthy observations:

  • two methods of assessing dietary protein poorly correlated (r=0.316).
  • energy and protein intake from diet records correlated (r=0.680), but not with UNA (r=0.216).
  • percent body fat did not correlate with actual weight (r=0.189).
  • urine creatinine negatively correlated strongly with percent body fat (r= -0.545).
  • albumin, transferrin and cholesterol correlated only weakly with each other, anthropometric measures and urine creatinine.
  • protein and energy correlated only weakly with albumin, transferrin, cholesterol, anthropometric measures and urine creatinine.
Author Conclusion:

These cross-sectional findings suggest that in patients with CRF, dietary protein and energy intakes and serum and anthropometric measures of protein/kcal nutritional status progressively decrease as GFR decreases. The reduced protein and energy intakes, as GFR falls, may contribute to the decline of many of the nutritional measures.

The serum creatinine levels of patients in this study were rather low, averaging 2.4+1.2 and 2.0+1.1 mg/dL in men and women respectively. A large number of patients with these serum creatinine levels may be managed by physicians who perceive the patients to be clinically stable and not in need of nutritional intervention. Moreover, physicians who are not nephrologists often treat patients with this range of serum creatinine concentrations. However, the results of the present study indicate that these patients, and particularly those with a GFR <21 mL /min/ 1.73m2 frequently show evidence for nutritional deterioration.

If nutritional management to prevent or treat protein calorie malnutrition is considered to be beneficial in these patients, it would be necessary to develop strategies to educate both nephrologists and nonnephrologist physicians with regard to the rationale and methods for the nutritional management of these patients.

Funding Source:
Government: NIH, NIDDK
Reviewer Comments:

GFR was factored by body surface area, therefore correlations between GFR and factors related to body weight (ie, BMI) were statistically influenced, and relationships would have been statistically stronger if factored by standard body weight (per authors' discussion).

Dietary intake was factored by standard body weight, therefore correlations between intake and anthropometric measures were stronger than if they had been factored by actual body weight (per authors' discussion).

Statistical analyses explained in great detail along with rationale of methods used.

Very strong study providing useful data towards furthering the understanding of relationships between GFR, nutritional factors and anthropometrics when attempting to eliminated PEM in predialysis patients.

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) N/A
  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) N/A
 
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? 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? N/A
  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.) N/A
  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? N/A
  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? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  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? 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? 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