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 develop and use a “uremic score” as a marker of uremic toxicity, and to correlate this score to other markers of renal function in an attempt to aid the clinician in determining when to initiate dialysis.

Inclusion Criteria:

Predialysis patients.  No selection criterion.  No subjects on low protein diets.

Exclusion Criteria:
None mentioned.
Description of Study Protocol:

Recruitment:  All subjects referred by nephrologist or other medical specialist for a pre-dialysis consult between Oct 1996 and Nov 1999.

Design:  Cross-sectional study.

Blinding used:  not applicable - lab tests.

Intervention:  mathematical manipulation of numerous variables in order to determine best clinical indications for initiating dialysis.

Statistical analysis:

  • mean+SD, P<0.05 indicates statistical significance
  • differences between means of continuous variables analyzed using unpaired t-tests (two-tailed)
  • Mann-Whitney test to compare independent variables without normal distribution
  • curve estimation analysis for best fit equation between clinical assessment of RF and uremic score
  • multiple logistic regression analysis for independent associations in determining malnutrition severity
  • Ccr correlated to Kt/V urea to investigate discrepancies between the 2 parameters of RF
  • methods for evaluating RF, to determine best fit correlations for "uremic score" using sex, age (> or < 65 years old), >1 comorbidity, severity of anemia (Hct >30, 25-30, or <25%).
Data Collection Summary:

Timing of measurements:  All data was collected on subjects during their first visit, before initiation of dialysis or erythropoietin.

Uremic score: defined by uremic symptoms and nutritional status as determined by a questionnaire and physical exam. Composed of sum of uremic symptoms, subjective global assessment, albumin and protein of non-protein nitrogen appearance (urine) with scores ranging from 0 to 8.

1. Uremic symptoms: anorexia, nausea or vomiting, decreased physical activity, edema, dyspnea or ortopenia, pruritis, bone pain, weakness, echimosis and/or epistaxis, muscle cramps, restless legs, diurnal somnolence, nocturnal insomnia, myoclonias, uncontrolled hypertension or cold intolerance.  Scoring of uremic symptoms as follows:

  • 0-4 symptoms=0 points
  • 5-9 symptoms=1 point
  • >9 symptoms=2 points

2. Subjective global assessment (SGA): determined by following information: history of weight changes, modifications in diet, presence of anorexia, nausea or vomiting, loss of subcutaneous fat, muscle wasting, or edema.  (Subjectively) evaluated and scored according to severity:

  • no malnutrition=0
  • mild-moderate malnutrition=1
  • severe malnutrition=2

3. Serum albumin,  scored based on albumin levels as follows:

  • >4 g/dL=0
  • 3 to 4 g/dL=1
  • <3 g/dL=2

4. Protein of non-protein nitrogen appearance (PNPNA) calculated using 24 hr urine collections to determine urea excretion and urea nitrogen generation rate, for the purpose of representing protein catabolic rate.  Scoring of PNPNA, normalized for ideal body weight:

  • >0.9 g/kg/d=0
  • 0.6-0.9 g/kg/d=1
  • <0.6 g/kg/d=2

Renal function calculations:

  • urea, creatinine, and total proteins determined from 24-hr urine,
  • used to calculate creatinine clearance (Ccr) and urea clearance (Cu),
  • sum of Ccr and Cu divided by 2 (Ccr-Cu) used as an approximation of GFR.
  • Kt/V urea expressed as weekly value, based on Cu and urea distribution volume.

Biochemical (n=61):

  • serum transferrin
  • total cholesterol
  • serum bicarbonate
  • serum C-reactive protein
  • hematocrit 

Dependent variables:

  • severity of uremic symptoms and malnutrition correlated to renal function measures.

Independent variables:

  • Uremic symptoms
  • Subjective Global Assessment
  • Serum albumin
  • Protein of non-protein nitrogen appearance (PNPNA)
  • Measures of renal function
  • Biochemical variables

For determinants of malnutrition severity: age, gender, >1 comorbidity, Ccr-Cu, Kt/V urea, hematocrit, serum bicarbonate, proteinuria.

Control variables:

  • Standard body surface area of 1.73 m2
  • IBW: 24 for males, 23 for females
  • LBM calculated from 24-hr creatinine excretion
  • Comorbidities that effect nutritional status, ie inflammatory disease, CHF, DM, etc.
Description of Actual Data Sample:

Initial N:  201 subjects (102 female, 99 male)

Attrition (final N):  201

Age:  mean 63+13 yr (16-84 yr).

Ethnicity:  not mentioned.

Other relevant demographics:  na

Anthropometrics (measures expressed as percentiles of a healthy Spanish reference population):

  • BMI
  • MAC
  • MAMC
  • TSF

Location:  Badajoz, Spain.

Summary of Results:

The causes of renal failure were:
  total n=201

Unknown

27

Primary glomerulonephritis

38

Diabetic nephropathy

51

Chronic interstitial nephritis

42

Ischemic nephropathy

25

Adult polycystic disease

18

Comorbidities of study population  (>50% had at least one major comorbid condition.)

  • 65 had diabetes mellitus
  • 14 had a chronic infectious or inflammatory disease
  • 12 had CHF
  • 6 had a malignancy
  • 4 had CPOD
  • 1 had liver cirrhosis
  • 55 (27%) had at least one atherosclerotic complication
  • 61 had nephrotic proteinuria.

SGA

  • no malnutrition: 128 (64%)
  • mild-moderate: 62 (31%)
  • severe: 11 (5%)
Selected characteristics of subgroups, as determined by SGA:
 

Malnutrition

  None (n=128)

Mild-Moderate (n=62)

Severe (n=11)

Age, yr

61±15

66±10

67±9

Ccr (ml/min/1.73 m2)

14.6±5.1a

12.3±4.1

10.5±4.5

Cr-Cu (ml/min/1.73 m2)

10.8±3.5a

9.1±2.9

7.9±3.1

Kt/V urea weekly 2.03±0.76b 1.73±0.56 1.59±0.73

Hct, %

31.3±5b

29.0±5.6

28.0±3.9

BMI

29.2±5.8

27.7±5.3

22.6±4.0a

MAMC

43±24a

24±26c

6±8

TSF

49±27a

30±29c

7±11

PNPNA (g/kg IBW/day) 1.04+0.32a 0.88+0.22 0.76+0.21

Albumin (g/dL)

3.8±0.4a

3.6±0.6

3.4±0.4

n subjects with comorbidity 45/128 (35%) 47/62 (76%) 10/11 (91%)

a P<0.05, compared to other 2 subgroups

b P<0.05, compared to mild-moderate

c P<0.05, compared to severe

 

Best determinants for presence of malnutrition:

 95% CI Odds ratio P

Comorbidity (4.73-22.37)

10.29

<0.0001

Ccr-Cu (0.98-0.94)

0.96

=0.0015

Hematocrit (0.85-0.98)

0.91

=0.014

 

Significant correlations in RF parameters:

  • Kt/V urea and Ccr (r=0.76, P<0.001)
  • Ccr and Cu (r=0.79)

Significant correlations in relationships between RF and protein catabolic rate:

  • Kt/V urea and PNPNA (r=0.53, P<0.0001)
  • PNPNA and Ccr-Cu (r=0.51, P<0.0001) 

Mathematical relationships between methods for assessing correlation between RF and "uremic score:"

  • no correlation between serum creatinine and uremic score (r=0.028).
  • Statistically significant correlations were found between Ccr or Ccr-Cu and the "uremic score."  Kt/V urea was less predictable and differed between male and female subjects.  Severity of anemia, based on Hct criteria mentioned above, affected the relationship between the uremic score and Ccr-Cu.  However, the score increased sharply (ie, worsened) when Ccr fell <13 or Ccr-Cu fell <10 ml/min.
Author Conclusion:

The relationship between the potential detrimental effects of uremia with renal function in pre-dialysis renal failure patients is not linear, and is strongly influenced by comorbidity and the severity of anemia. The mean of creatinine and urea clearance (Ccr-Cu), corrected for standard body surface area, appears to be a reliable method for establishing the severity of chronic renal insufficiency.

Nephrologists should be aware that potential uremic symptoms and malnutrition become sharply more intense when the renal function, determined by the mean of creatinine clearance and urea clearance (Ccr-Cu), falls below 10 ml/min, irrespective of age or sex.

Funding Source:
University/Hospital: Hospital Universitario Infanta Cristina,
Reviewer Comments:

The creatinine clearance was quite low; nutrition intervention and/or renal replacement therapy are now recommended before it becomes this low.

Detailed methods and statistical analysis sections with formulas, references and/or rationale explained for most calculations.  Authors' rationale for weighing specific variables not discussed, validity and/or reliability of "uremic score" not discussed.  No reporting of "uremic score" outcomes, potential correlations to indicators of malnutrition not discussed. 

Timing of 24 hr urine collection not specified.

Questionable results reported for MAC, MAMC, and TSF of severely malnourished subgroup, per SGA.  Therefore, unknown whether this is a misprint or possibly could affect statistical calculations.

Not clear why higher levels of PNPNA equal lower score.  Would expect higher number representing protein catabolism to receive high score.

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? Yes
2. Was the selection of study subjects/patients free from bias? ???
  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? ???
  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? ???
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? N/A
  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? 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? Yes
  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? ???
  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? ???
  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? 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? ???
  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? ???
  7.1. Were primary and secondary endpoints described and relevant to the question? N/A
  7.2. Were nutrition measures appropriate to question and outcomes of concern? ???
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? ???
  7.5. Was the measurement of effect at an appropriate level of precision? ???
  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? ???
  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)? ???
  8.6. Was clinical significance as well as statistical significance reported? ???
  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