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CKD: Nutrition Status Parameters (2010)

Citation:

Kopple JD, Berg R, Houser H, Steinman TI, Teschan P. Nutritional status of patients with different levels of chronic renal insufficiency. Modification of Diet in Renal Disease (MDRD) Study Group. Kidney Int. 1989; 36(suppl 27): S184-S194.

Worksheet created prior to Spring 2004 using earlier ADA research analysis template.
PubMed ID: 2636655
 
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:

This pilot phase purpose was done:

  1. To examine the feasibility of a full scale study that would evaluate wherether low protein, low phosphorus diets can retard the progression of renal failure in patients with chronic renal disease.
  2. To examine whether these diets will maintain good nutrition status.

To answer the following questions:

  1. Did the patients in the MDRD pilot study develop protein-calorie malnutrition?
  2. Is the incidence or severeity of malnutrition related to the degree of renal insufficiency (that is, the level of glomerular filtration rate).
  3. Is the dietary energy intake related to the severity of malnutrition?
Inclusion Criteria:
  • Evidence of chronic progressive renal insufficiency
    • a decrease in inverse serum creatinine of at least 0.003 dl/mg/month
  • Glomerular filtration rate between 8 and 80 ml/min/1.73 m2
Exclusion Criteria:
  • Chronic serious medical illness (malignancy, chronic heart or liver failure, collagen vascular disease, insulin dependent diabetes, uncontrolled hypertension)
  • Severe psychiatric illness
  • Evidence the patient would not comply to the study protocol 
  • Use of immunosuppressive medications or corticosteroids 
  • Proteinuria >10 g/d or greater
  • Malnutrition as evidenced by
    • body weight <80% or >160% of standard body weight
    • or serum albumin <3.0 g/dL
Description of Study Protocol:

Recruitment:

Methods not specified.

Design:

  • First entered a baseline period that lasted at least 3 months (median = 4.5 months)
    • Patient's clinical and nutritional status assessed
    • Patient's social and demographic situation and GFR assessed
    • Assigned to Study A if GFR was 25 ml/min/1.73 m2 or greater
      • Patient's whose usual protein intake was less than 0.9 g/kg/day were excluded
      • Prescribed protein intake was designed to be similar to the patient's usual protein intake
      • Median baseline protein prescription was 1.2 g/kg/day
    • Assigned to Study B if GFR was 8-24 ml/min/1.73 m2
      • Prescribed protein intake was designed to be similar to the patient's usual protein intake
      • Median baseline protein prescription was 1.1 g/kg/day
  • At the end of baseline, patients assigned in random fashion, to recieve one of three diets:
    • Study A patients received diets M, L, or K
    • Study B patients received diets L, K, or J
  • Diet descriptions:

 

Study Diets Description

Diet protein (g/kg/day) phosphorus (mg/kg/day)
M 1-1.4 16-20
L 0.58 5-10
K 0.28 plus 2.8/10 kg body weight per day of ketoacid mixture EE* 4-9
J 0.28 plus 2.16 g/10 kg/day of essential amino acids** 4-9

*Cernep Synthelabo, Meudon-La_Foret, France

**Aminess Novum, KabiVitrum, Alameda, California, USA

  • Prescribed energy intake:
    • Designed to equal the patient's average daily energy intake during the baseline period, as determined from diet records.
    • If the patient lost weight, the prescribed energy intake was increased
    • If the patient weighted more than 120% of desirable body weight and voluntarily expressed a desire to lose weight, the prescribed energy intake was reduced
    • When the prescribed daily energy intake for a patient was changed for the reasons described above, the Harris-Benedict equation for basal energay expenditure and the patient's average daily activity, assessed by interviews, were used to develop the new dietary energy prescription.
  • Other interventions
    • One multivitamin-zinc capsule
      • provided (mg) thiamine 1.5, riboflavin 1.7, niacinamide 20, pyridoxine HCl 10, pantothenic acid 10, vitamin B 12 0.006, biotin 0.3, ascorbic acid 60, folic acid 1.0, cholecalciferol 0.005, vitamin E 6, zinc 8.
    • Calcium carbonate tablets or suspension to raise total daily calciumj intake (diet and supplements combined) to 1450 to 1550 mg/day.
    • If serum phosphorus was elevated in spite of attempts to lower phosphorus intake:
      • aluminum or calcium phosphate binders given
    • If serum albumin or transferrin decreased below previously established values, standardized interventions increased protein intake.
  • After patients assigned to each diet:
    • Monitored for follow-up period of 12.4 months (range 0 to 21.6)
    • During first 1-2.5 months:
      • patients trained by a dietitian:
        • procurement of foods for their new diets
        • development of menu plans and recipes
        • actual preparation of their assigned diets
    • Patients seen monthly by dietitian
      • At first visit:
        • carried out dietary interview
      • At each subsequent visit:
        • obtained 3 day dietary diary
        • 24 hour recall
        • anthropometric assessment
      • Used to assess energy intake:
        • food intake, estimated from three 24-hour dietary diaries and
        • one 24-hour diet recall
        • data entered by trained coders at the MDRD Pilot Study Nutrition Coordinating Center  (Director, H. Houser, M.D.) using standardized procedures
        • used HVH-CWRU Nutrient Daya Base (Revision 9A, 1987, Case Western Reserve University, Cleveland, Ohio)
      • Protein intake calculated:
        • from 24-hour urine urea nitrogen
        • formula used:  protein intake (g/day) = 6.25 x [24-hour urine urea nitrogen (g/day) + (0.031 g N/kg/day) x desirable body weight (kg)] + urine protein (g/day) in excess of 5 g/day
  • Anthropometrics:
    • Body weight
      • measured with beam balance scale with accuracy to within 0.1 kg
      • standard weights used to calibrate the scale
      • When data expressed per kg body weight, this refers to the desirable body weight for an individual of similar age, height, sex and frame size as determined from the Metropolitan Life Insurance tables
      • When data are expressed per 1.73 m2 body surface area, this value is calculated from the patient's height and body weight as determined from the formula:
        • BSA = (patient's actual weight inkg)0.425 x (height in cm)0.725 x 0.007184
    • Height
      • Measured using a stature measurement board with a non-stretchable steel measuring tape and a movable head board that was attached to a wall or other vertical flat surface
      • Tape marked in 1 mm increments
    • Bicondylar elbow width to estimate frame size
      • Measured with a bicondylar vernier caliper (Holtain)
    • Biceps, triceps, and subscapular skinfold thicknesses
      • Measured with a Lange skinfold caliper
    • Mid-arm circumference
      • Used steel measuring tape
    • Percent standard weight
      • 1983 Metropolitan Height and Weight tables
      • The midpoint of the weight range for a given height and frame size (determined from elbow breadth) was defined as the standard weight
    • Total body fat estimated from the equation:
      • % body fat = (4.95/Y - 4.5) x 100
      • Y = body density
      • Y = c - a(x)
        • x = log of the sum of the triceps, bieps, and subscapular skinfold thickness (mm)
        • c and a are coefficients which vary according to the age and sex of the individual
    • Arm muscle area:
      • AMA (cm2) = [(MAC (cm) - (pi x TSF (cm))]2 divided by 4pi  - K
      • MAC = midarm muscle circumference
      • TSF = triceps skinfold thickness
      • pi = 3.1416
      • K is a coefficient which is 10 for males and 6.5 for females
  • Dietitian training
    • All underwent at least 2 days of training at the MDRD Pilot Study Nutrition Coordinating Center
    • Instructed in a standarized protocol for:
      • training patients in the preparation and use of the diets
      • taking dietary histories
      • obtaining activity histories
      • performing anthropometry
      • using computers to estimate the patients' nutrient intakes for diet planning
    • Were certified as competent in each of these activities before they were eligible to work with the study patients
  • Serum and urine biochemistry measurements performed at a Central Biochemistry Laboratory in Department of Biochemistry at the Cleveland Clinic Foundation

Blinding used (if applicable):  none

Intervention (if applicable): see above

Statistical Analysis:

  • Data Coordinating Center for the MDRD Study located at the Cleveland Clinic Foundation
  • Analysis of variance for significance p < 0.05
    • for significance among groups of data, Student's t-tests using pooled estimates of variance used to examine group differences
  • linear regression analyses 
  • no adjustment made in the P values for the numbers of different nutritional parametes evaluated in this survey
  • variability is expressed as standard error of the mean
  • Pearson's correlations

 

  

 

Data Collection Summary:

Timing of Measurements:  Monthly

Dependent Variables

  • Measured monthly:
    • serum total proteins, albumin, transferrin, cholesterol, triglyceride
    • urine creatinine, urea nitrigen, protein
  • Anthropometrics:
    • Body weight
    • Height
    • Bicondylar elbow width to estimate frame size
    • Biceps, triceps, and subscapular skinfold thicknesses
    • Mid-arm circumference
    • Percent standard weight
    • Total body fat
    • Arm muscle area
  • Energy and protein intake
  • GFR

Independent Variables:

  • energy and varying levels of protein intake

Control Variables:

  • physical activity
  • phosphorus binders as needed to control phosphorus
  • all patients received MVI and mineral supplement

 

 

Description of Actual Data Sample:

Initial N: 95 subjects

Attrition (final N):  95 subjects

Age:  not mentioned

Ethnicity:  not mentioned

Other relevant demographics:

Mean GFR at end of baseline:  21.6 +/- 1.2 (range, 8.0 to 56.0)

Anthropometrics:

Anthropometry in men and women according to their final GFR
  > 25 10-24 <10 P
Men        
No. of subjects 14 20 22-23  
% Desirable wt

117 +/-2.8

(107 +/- 1.1)a

110 +/-2.7

(106 +/-2.1)

110 +/- 2.6

(105 +/- 1.7)

NS

(NS)

BMI 26.6 +/-0.9 26.0 +/-0.8 25.8 +/-0.6 NS
Triceps skinfold, mm 16.9 +/-2.0 17.2 +/-1.4 16.0+/-1.6 NS
Biceps skinfold, mm 7.7 +/-1.0 7.6 +/- 1.0 7.0 +/- 0.8 NS
Subscapular skinfold, mm 19.2 +/-2.0 17.8 +/-1.1 17.3 +/-1.6 NS
% body fat 28.0 +/- 1.5 28.6 +/- 1.4 27.0 +/-1.4 NS
Arm muscle area cm2 51.3+/-2.6 45.7+/-2.5 42.0 +/-2.7 NS
Women        
No. of subjects 6 19 13  
% Desirable weight

102+/-5

(96+/-4.7)

112+/-5

(100+/-2.9)

105+/-6

(97+/-3.6)

NS

(NS)

BMI 22.5+/-1.3 25.7+/-1.3 24+/-1.4 NS
Triceps skinfold,mm 22.5+/-3.4 21.9 +/-2.2 20.2+/-2.2 NS
Biceps skinfold,mm 11.5+/-3.1 10.1+/-1.4 8.8+/-1.3 NS
Subscapular skinfold,mm 20.7+/-4.0 18.8+/-2.2 17.2+/-2.9 NS
% body fat 33.6+/-2.5 34.2+/-1.7 31.6+/-3.7 NS

aNumbers in parentheses are for patients with a desirable body weight of 115% or less.  Only values for desirable body weight and for those nutritional parameters with a significant difference between groups are shown.

Locations: 

  • Beth Israel Hospital, Boston, Massachusetts
  • Brigham and Women's Hospital, Boston, Massachusetts
  • Harbor-UCLA Medical Center, Torrance, California
  • Johns Hopkins Hospital, Baltimre, Maryland
  • Massachusets General Hospital, Boston, Massachusetts
  • New England Medical center Hospital, Boston, Massachustetts
  • University of Iowa Hospitals and Clinics, Iowa City, Iowa
  • University of Southern California, Los Angeles, California
  • Vanderbilt University Medical Center, Nashville, Tennessee

 

 

Summary of Results:

 

Nutritional parameters in patients according to their final GFR

(men and women combined)

  greater than or equal to 25 10-24 less than 10 p value
number of subjectsa 20 39e 36  
energyg intake kcal/kg/day

28.6 +/- 2.0

(30.9 +/- 2.8)*

22.9 +/- 1.7e

(24,2 +/- 1.7)e

22.9 +/- 1.3e

24.4 +/- 1.6e

0.02

(0.07)

serum creatinine mg/dl 2.1 +/- 0.1 3.8 +/- 0.2 8.1 +/- 0.4e <0.001
serum albumin g/dl 4.2 +/- 0.1 4.2 +/- 0.1  4.2 +/- 0.1 NS
serum transferrin mg/dl

294 +/- 13

(290 +/- 15)

271 +/- 8

(274 +/- 11)

246 +/- 8e

(252 +/- 11)

0.005

(NS)

serum total cholesterol mg/d 208 +/- 10 [18] 216 +/- 8 196 +/- 9 [25] NS
serum triglycerides 158 +/- 20 [18] 213 +/- 17 172 +/- 15 [25] 0.03
urine protein g/day

0.7 +/- 0.2

(0.4 +/- 0.1)

1.6 +/- 0.3

(1.1 +/- 0.3)

2.3 +/- 0.4 [35]e

(2.1 +/- 0.5)e

 

0.03

(0.02)

aRefers to the number of men and women in each group unless a different value is given in brackets

e Significantly different from the group with GFR > 25 ml/min/1.73 m2, p < 0.05

*numbers in parentheses are for patients with a desirable body weight of 115% or less.  Nutritional parameters are shown for this subgroup only if there was a statistically significant difference or a trend between groups. The numbers of subjects in the groups with a GFR > 25, 10 to 24, and < 10 ml/min/1.73 m2 were 12, 25, and 17 to 25, respectively.

 

Antrhopometry in men and women according to their final GFR:

  • no significant differences except:

Variables

> 25

10-24 <10

Statistical Significance of Group Difference

 Creatinine:height ratio for men

mg/day/cm

 8.7 +/- 0.5

(8.7 +/- 0.5)

 7.2 +/- 0.4a

(6.9 +/- 0.4)a

6.4 +/- 0.4a

(5.9 +/- 0.4)a

 0.001

(0.001)

 aSignificantly different from the group with GFR > 25 ml/min/1.73 m2, p < 0.05

  • For women, no significant differences
  • When men analyzed separately from women, significant positive correlations observed with the GRF:
    • % standard weight
    • arem muscle area
    • creatinine: height ration

 

Energy intakes at the end of baseline

  • In women, energy intake positively and strongly correlated (p<0.005) with the GFR
    • correlation coefficient 0.53

Correlation coefficients for nutritional parameters with GFR final visit
  All patients men women
No. of subjects 94-95 56-57 38
energy intake

0.27, p < 0.05

(0.25)a

0.16

(0.13)

0.48, p<0.005

(0.50), p<0.05

serum transferrin

0.32, p<0.005

(0.25)

0.31, p<0.05

(0.13)

0.38 p<0.05

(0.45), p <0.05

arm muscle area 0.19 0.32, p<0.05 -0.10
creatinine:height ratio

0.42, p<0.005

(0.48, p<0.005)

0.47, p<0.005

(0.54, p<0.005)

0.26

(0.40, p<0.05)

urine protein

-0.21, p<0.05

(-0.32, p<0.05)

-0.30, p<0.05

(-0.34, p<0.05)

-0.10

(-0.31)

avalues in parentheses indicate correlation coefficients for patients with a desirable body weight of 115% or less (29-37 males, 25-26 females); only parameters are shown for which there was a significant correlation

  • The relationship between protein intake and GFR was not examined at this time because the patients had been randomly prescribed different levels of dietary protein.
  • They estimated that 12 or fewer patients made voluntary, and often transient, attempts to reduce energy intake in order to lose weight.
    • For technical reasons, it was difficult to identify these individuals
    • It is possible that the voluntary reduction in energy intake was a cause for the correlations between nutritional parameters and GFR
    • They reanalyzed the realtionships in the men and women with a desirable body weight of 115% or less and found no difference in the relationship pattern.

Energy intake throughout treatment period:

Mean energy intake was significantly less than prescribed for men and women combined:

Group

 

Prescribed

Actual

P

  n

kcal/kg

 

A + B

95

29.8+/-0.53

24.8+/-0.69

<0.005

A 29

31.1+/-0.95

26.5+/-1.07

<0.005

B 66

29.2+/-0.62

24.0+/-0.86

<0.005

 

For men only:

Group

 

Prescribed

Actual

P

  n

kcal/kg

 

A 20

31.2+/-1.11

25.8 +/- 1.09

<0.005

B 37

30.5 +/-0.90

25.3 +/- 1.21

<0.005

For women only:

Group

 

Prescribed

Actual

P

  n

kcal/kg

 

A 9

30.9+/-1.94

28.1 +/- 2.48

<0.05

B 29

27.4 +/-0.73

22.4 +/- 1.15

<0.005

  • The average energy intake of most patients throughout the treatment period was less than their prescirbed intake
    • The mean of the average intakes throughout their follow-up period:  5.0 +/- 0.47 kcal/kg/day less (16.8% less) than the mean of the average prescribed intake.
  • There were significant inverse correlations between the patients’ mean energy intake throughout the study period:
    • for age (r= -0.27, P<0.05) 
    • final study values for:
      • TSF (r = -0.24, P<0.05)
      • subscapular SF (r = -0.21, P<0.05)
      • % body fat (r = -0.35, P<0.005)
      • BMI (r=-0.30, P<0.005)

Protein intakes

Mean protein intakes as determined by urinary nitrogen were above prescribed amounts (except for the higher protein study group, M):

Group

Protein + Amino Acid Intake

 

n

diet

g/kg/desireable body wt

Men 57  

0.81+0.02

Women

38

 

0.70+0.02

A

11

M

1.04+0.04

  10 L

0.91+0.06

 

8

K

0.69+0.05

A 29 all

0.90+0.04

B

21

J

0.72+0.03

  23 L

0.72+0.03

  22 K

0.69+0.03

B

66

all

0.71+0.02

Author Conclusion:

The MDRD patients remained well nourished during the course of the feasibility study. However, estimated dietary energy intake was low and there was a tendency for body mass and the creatinine-height ratio to ? as the study progressed and the GFR ?. This was particularly evident in subjects with a GFR< 24 ml/min/1.73 m2 .

Serum transferrin was positively correlated with the level of GFR and was significantly ? in subjects with a GFR <10 ml/min/1.73 m2 .

Further studies will be necessary to examine the causes for this propensity for protein-calorie malnutrition, the mechanisms responsible for this evidence of ? energy intake, and whether the ? energy intakes are the principal cause of the malnutrition.

Funding Source:
Government: NIDDK, NIH
Reviewer Comments:

This study shows the importance of assessing patients with pre end stage renal disease for energy intake and factors that interfere with adequate energy intake to prevent protein-calorie 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) 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? 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? 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