EAL

CKD: Hypertension and Hyperlipidemia (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to identify preclinical atherosclerosis in predialysis patients and to assess possible interactions between CVD, inflammation, malnutrition, Lp (a), and oxidative stress.

Inclusion Criteria:

1. CRF but not on maintenance dialysis

Exclusion Criteria:

1. >70 yr of age

2. Hospitalized with clinical signs of overt infection and/or acute vasculitis at the time of admission.

Description of Study Protocol:

Recruitment:

Recruitment methods not described.

Design: Cross-sectional study.

Blinding Used (if applicable): Not applicable.

Intervention (if applicable): Patients interviewed and examined close to start of dialysis treatment.

Statistical Analysis

Comparison between 2 groups performed using Student's t test for normally distributed variables, whereas the Mann Whitney U test was used for non-normal distributed variables. Comparisons between 2 groups for nominal variables were made by the Fisher exact test. Correlations were performed by linear regression analysis. However, for non-normally distributed variables, correlations were performed with the Spearman rank test. Independent associations between 1 dependent variable and more than 2 independent variables were assessed by multiple and logistic regression analysis.

Data Collection Summary:

Timing of Measurements

Subjects were interviewed and examined close to the start of hemodialysis.

Dependent Variables:

Carotid intima-medial thickness, lumen diameter and calculated intima-media area measured by carotid B-mode ultrasonography of the right and left carotid arteries
DEXA for body composition
Blood pressures were determined by a 24-hr ambulatory blood pressure measurement or a mercury sphygmomanometer in the supine position
24- hr urine sample for creatinine, urea and albumin
Fasting blood sample was taken for the following determinations: albumin, CRP, creatinine, urea, lipids, Lap (a), ape (a) isoform size, apolipoprotein A-I (apo A-1), apo B, vitamin E, autoantibodies against oxidized LDL, fibrinogen and TNF-a

Independent Variables:

Nutritional status was assessed using subjective global assessment (SGA) using 6 subjective assessments: weight history, anorexia, vomiting, edema, loss of subcutaneous fat and muscle wasting

Control Variables:

Smoking history: current/former smokers or nonsmokers

Description of Actual Data Sample:

Initial N: 109 patients (66 males and 43 females) with CRF were subjects.

Attrition (Final N): 109

Age: 52 +/- 1 years (range 23 - 69)

Ethnicity: not mentioned

Other relevant demographics:

Baseline data:
Age, y	52+1 (23-69)
BMI	24.4+0.4
Creatinine Clearance, ml/min	7+1
Serum albumin, g/L	32.2+0.9 to 34.8+0.8

Anthropometrics: Causes of renal failure were chronic glomerulonephritis (34%), diabetic nephropathy (28%), polycystic kidney disease (14%), and other (20%). 22 healthy subjects closely matched to the patients for age and gender also had carotid B-mode ultrasonography measurements for comparison.

Location: Huddinge University Hospital, Stockholm, Sweden

Summary of Results:

Other Findings

24-hr urine parameters
urea excretion, mmol	209+8
albumin, mg	2883+315
Vascular disease, %	31
Blood pressure
Systolic, mm Hg	145+2
Diastolic, mm Hg	85+1
Medications Antihypertensives, %	85

Compared with healthy controls, CRF patients had an increased mean carotid intima-media area, and a higher prevalence of carotid plaques.

Carotid B-mode ultrasonographic data in patients with CRF and in age and sex matched controls
	CRF	Controls	P
	N=109	n=22
Age, yr	51+1	50+2	NS
Males, %	60	59	NS
Plaques (carotid), %	72	32	<0.001
Intima-media Thickness (mm)	0.74+0.02	0.64+0.03	<0.01
Diameter (mm)	7.0+0.1	5.8+0.1	<0.0001
Area (mm)	18.3+0.6	13.2+0.7	<0.0001

The prevalence of malnutrition was 44% and 32% of all patients had an acute phase response (CRP >10 mg/L).

Malnourished patients had increased CRP values (23+3 vs. 13+2 mg/L, P<0.01) elevated calculated intima-media area (20.2+0.8 vs. 16.9+0.7 mm2, P<0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P<0.0001) compared to the well-nourished patients.

The presence of carotid plaques was significantly associated with age (P<0.001), log oxidized LDL lipoprotein (P<0.01) and small apo (a) isoform size (P<0.05) in a multivariate logistic regression model.

Author Conclusion:

The results from this cross-sectional study suggest that rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms such as malnutrition, inflammation, oxidative stress, and genetics.

There was a high prevalence of malnutrition (44%), inflammation (32%) and carotid plaques (72%) in this population of 109 predialysis patients. Malnourished predialysis patients were more likely to smoke and have increased plasma Lp (a) levels, increased oxidative stress, and an enhanced acute-phase response.

Funding Source:

Government:

Swedish Medical Research Council

Industry:

Baxter Extramural Grant Program

Pharmaceutical/Dietary Supplement Company:

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

The subjects in this study appeared to have more severe renal failure (creatinine clearance and albuminuria) and more were malnourished (serum albumin, SGA) at the time of initiation of dialysis than is customary in the US.

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