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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 29  |  Issue : 2  |  Page : 280-284

Carotid intima–media thickness in children with end-stage renal disease on hemodialysis


Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission13-Nov-2014
Date of Acceptance09-Dec-2014
Date of Web Publication18-Oct-2016

Correspondence Address:
Zein A Saber Omar
Shebin El Kom, Menoufia 32511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.192440

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  Abstract 

Objectives:
The aim of this study was to study carotid artery intima–media thickness (CIMT) in children with end-stage renal disease who are undergoing hemodialysis.
Background:
Cardiovascular morbidity and mortality are common in patients with end-stage renal disease.
Patients and methods:
The study involved 60 children divided into three groups: 20 children had chronic kidney disease on conservative therapy (group I) (predialysis), 20 children were undergoing hemodialysis (group II), and 20 children constituting the control group (group III). All participants were subjected to detailed history taking and clinical examination. Laboratory investigations included evaluation of complete blood picture, serum creatinine, blood urea, calcium (Ca), phosphorus (PO4), uric acid, C-reactive protein, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, total bilirubin, and albumin. The glomerular filtration rate was calculated from serum creatinine using the Schwartz formula. All participants underwent measurements of CIMT by means of ultrasonography.
Results:
There was a significant increase in CIMT in group I and group II when each group was compared with group III. CIMT had a significant positive correlation with systolic and diastolic blood pressure, C-reactive protein, serum urea, creatinine, parathyroid hormone, total bilirubin level, and total cholesterol levels. CIMT had a significant negative correlation with BMI, hemoglobin level, hematocrit, estimated glomerular filtration rate, serum calcium, albumin, and high-density lipoprotein levels.
Conclusion:
Chronic kidney disease is associated with increased CIMT. This suggests that even in young children uremia and/or metabolic alterations have a profound impact on the arterial structure and function leading to cardiovascular morbidity and mortality.

Keywords: carotid artery intima–media thickness, end-stage renal disease, hemodialysis


How to cite this article:
Elshafie AM, Bahbah MH, Elnemr FM, Ragab SM, Saber Omar ZA. Carotid intima–media thickness in children with end-stage renal disease on hemodialysis. Menoufia Med J 2016;29:280-4

How to cite this URL:
Elshafie AM, Bahbah MH, Elnemr FM, Ragab SM, Saber Omar ZA. Carotid intima–media thickness in children with end-stage renal disease on hemodialysis. Menoufia Med J [serial online] 2016 [cited 2019 Nov 18];29:280-4. Available from: http://www.mmj.eg.net/text.asp?2016/29/2/280/192440


  Introduction Top


Cardiovascular morbidity and mortality are common in patients with end-stage renal disease (ESRD). Because of the increased survival of children on renal replacement therapy, long-term cardiovascular complications of uremia are of great concern. Among these cardiovascular complications, valvular and myocardial calcification and atherosclerosis have great significance [1].

Multiple reasons for increasing the incidence of cardiovascular mortality and morbidity in ESRD patients have been considered, such as dyslipidemia, hypertension, low-grade inflammation, hyperhomocysteinemia, and disturbance of calcium and phosphorus homeostasis. Uremia accelerates atherosclerosis by inducing abnormal lipid metabolism and low-grade inflammation [2].

Uremia-associated inflammation due to renal or systemic inflammatory disease, heart failure, and dialysis-dependent procedures may exacerbate atherosclerosis in chronic kidney disease (CKD) patients [3].

Detecting asymptomatic patients at risk for atherosclerosis, who need more preventive modalities and medical intervention, can reduce cardiovascular diseases in children. Carotid artery intima–media thickness (CIMT), an early marker of generalized atherosclerosis, can be evaluated by B-mode ultrasonography [4].

The aim of this work was to study CIMT in children with ESRD who were on hemodialysis.


  Patients and Methods Top


This study was conducted in the pediatric hemodialysis unit in the Pediatrics Department at Menoufia University Hospital during the period from September 2012 to March 2014.

The study was carried out on 60 children who were divided into three groups: group I (the predialysis group), group II (the dialysis group), and group III (the control group). Group I comprised 20 patients with chronic renal insufficiency (CKD stages 2, 3, and 4) due to different causes who were on conservative treatment and did not require dialysis. Group II comprised 20 patients with ESRD due to different causes who were on regular hemodialysis. Group III comprised 20 healthy children of matched age and sex who served as the control group.

All patients and controls were subjected to detailed history taking and thorough clinical examination. Anthropometric measures included the height and dry weight of each patient, measured using a standard protocol, and BMI, calculated as (weight in kg)/(height in m)2. Blood pressure was measured by the auscultatory method using a mercury sphygmomanometer with the patient in the semisetting position after 10 min of rest, in the nonfistula arm using an appropriately sized cuff. Systematic examination included skin, bone, chest, heart, abdominal, and neurological examination. Investigations included CBC, blood urea, serum creatinine, serum Ca, PO4, parathyroid hormone and uric acid, C-reactive protein (CRP), total cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total bilirubin, and albumin. The glomerular filtration rate was calculated by the Schwartz formula [5].

The CIMT was also measured as an indicator of atherosclerosis [6]. All assessments were made using ultrasonic diagnosis equipment (Power Vision 6000, Toshiba SSA-370 A; Hyogo, Japan) and a linear 7.5-MHz transducer. A skilled pediatric radiologist who was unaware of the clinical data examined all patients consecutively. All measurements were taken with the patient in the supine position under quiet conditions after 5 min of rest. After placing electrodes for three-lead orthogonal ECG, the examination was completed in 30–45 min for each patient. The Ethics Committee of the Faculty of Medicine, Menoufia University, approved the study protocol, and informed written consent was obtained from each participant. Results were collected, tabulated, and statistically analyzed with an IBM compatible personal computer using SPSS statistical package, version 20; SPSS Inc., Chicago, Illinois, USA).

Two types of statistical analyses were performed: descriptive statistical analysis and analytical statistical analysis. In descriptive statistics, data were expressed as number (n), percentage (%), mean (X), and SD. In analytical statistics, qualitative data were analyzed using the c 2-test, and whenever one cell (or more) of the expected was less than 5 Fisher's exact test was used. Normally distributed quantitative data were analyzed by means of the t-test (between two groups). Normally distributed quantitative data were analyzed by means of the analysis of variance test (between three or more groups), and the least significant difference test was used as the post-hoc test. Pearson's correlation was used to express the correlation between two quantitative variables. P values less than 0.05 were considered statistically significant.


  Results Top


There was a highly significant increase in the CIMT of patients on conservative treatment and dialysis compared with controls ([Table 1]).
Table 1: Carotid intima–media thickness of patients and controls

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Both patient groups had significantly higher urea and serum creatinine levels and significantly lower estimated glomerular filtration rate (eGFR) compared with controls. Patients on conservative treatment had significantly lower calcium and phosphorus levels compared with patients on dialysis, but no difference in parathyroid hormone level. Patients on conservative treatment had significantly higher calcium, phosphorus, and parathyroid hormone levels compared with controls. Patients on dialysis had significantly lower calcium level and significantly higher phosphorus and parathyroid hormone levels compared with controls. Both patient groups had significantly higher CRP levels compared with controls. Both patient groups had significantly lower albumin levels compared with controls. Uric acid levels did not differ between groups. Both patient groups had significantly higher serum total cholesterol level and significantly lower HDL level compared with controls, but no difference in triglycerides and LDL level ([Table 2]).
Table 2: Comparison of laboratory data between patients and controls

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It was found that there was a highly significant positive correlation between CIMT and systolic and diastolic blood pressure, CRP, serum urea, creatinine, parathyroid hormone, and total cholesterol levels. There was a highly significant negative correlation between CIMT and BMI, hemoglobin level, hematocrit, eGFR, serum calcium, albumin, and HDL levels ([Table 3]).
Table 3: Correlation between carotid intima–media thickness and clinical data and laboratory data in patients

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  Discussion Top


Cardiovascular disease is one of the most frequent causes of mortality and morbidity in adults and children with chronic renal failure. Increased arterial stiffness and atherosclerosis in patients with ESRD are strong independent predictors of all-cause and mainly cardiovascular mortality [7].

Despite an improvement in the survival of children with severe CKD, morbidity and mortality rates in these patients are still relatively high. The risk of death due to cardiovascular disease in children with ESRD is 1000-fold higher than that in the general pediatric population [8].

Also, uremia per se can increase the chance of atherosclerosis. The following nontraditional risk factors are involved in increasing the rate of atherosclerosis in ESRD patients: oxidative stress, fat mass, impaired one-carbon metabolism, endothelial dysfunction, uremic bone disease, vascular calcification, anemia, protein-energy wasting, and coagulation disorders [9].

The study revealed that there was a highly significant increase in CIMT of patients on dialysis (ESRD patients) compared with controls. This result was highly similar to those of Dursun et al. [7], Gheissari et al. [0], and Dvorkova et al. [1].

Kumar et al. [2] stated that CIMT in ESRD children was higher than that in the control group even before initiating dialysis. Higher values of mean CIMT in hemodialysis patients compared with controls have been shown by Brzosko et al. [3].

The study revealed that both patient groups had significantly higher urea and serum creatinine and significantly lower eGFR compared with controls. This agrees with the results of Dvorkova et al. [1] and El Shafie et al. [4], who found that there was a significant increase in urea and serum creatinine and decrease in eGFR of patients on conservative treatment and dialysis compared with controls.

The present study showed that there was a highly significant increase in phosphorus and parathyroid hormone level of patients on conservative treatment and dialysis compared with controls. This agrees with the results of Dursun et al. [7], who reported that there was a significant increase in parathyroid hormone level in dialysis and predialysis groups compared with controls.

Both patient groups had significantly higher CRP levels compared with controls, without significant difference between patients on conservative treatment and those on dialysis ([Table 3]). This agrees with the results of Dursun et al. [7], Gheissari et al. [0], Bakkaloglu et al. [5], and El Shafie et al. [6], who found that there was a significant difference in CRP between ESRD patients and controls; in contrast, Dvorkova et al. [1] reported that there was no significant difference in CRP between ESRD patients and controls. Elevated CRP is serological evidence of activated inflammatory response, which is considered a risk factor for cardiovascular disease in CKD.

It was found that both patient groups had significantly lower albumin level compared with controls. This agrees with the results of Dursun et al. [7], who found that there was a significant decrease in the albumin level of patients on dialysis compared with controls; in contrast, Dvorkova et al. [1] reported that there was no significant difference in albumin level between ESRD patients and controls.

The study revealed that both patient groups had significantly higher serum total cholesterol levels and significantly lower HDL levels compared with controls, without significant difference between patients on conservative treatment and those on dialysis. In contrast, there were no significant differences in triglycerides and LDL level between patients and controls. This agrees with the results of Gheissari et al. [0], who found that there was a significant increase in serum total cholesterol level of ESRD patients compared with controls.

This result does not agree with that of Dvorkova et al. [1], who reported that there was no significant difference in serum total cholesterol and HDL level between ESRD patients and controls. This may be because there was no difference between ESRD patients and control groups in terms of BMI. In the present study, however, the patients followed a special nutritional program and patients on conservative treatment and dialysis showed a significant decrease in BMI compared with controls, as well as significant increase in serum total cholesterol and HDL levels compared with controls.

Both patients groups had anemia, hypertension, dyslipidemia, uremia, hyperparathyroidism, hypoalbuminemia, and elevated CRP.

These factors are considered risk factors for cardiovascular disease with CKD. This agrees with the results of Staples et al. [7] and Wilson et al. [8], who reported that common risk factors for cardiovascular disease in children with CKD were traditional (hypertension and dyslipidemia) and uremia related (anemia, hyperparathyroidism, hypoalbuminemia, and elevated CRP).

It was found that there was a significant positive correlation between CIMT and systolic and diastolic blood pressure, CRP, serum urea, creatinine, parathyroid hormone, total bilirubin level, and total cholesterol levels.

There was a significant negative correlation between CIMT and BMI, hemoglobin level, hematocrit level, eGFR, serum calcium, albumin, and HDL levels.

CIMT is positively correlated with non-HDL cholesterol in both predialysis and dialysis patients [9]. Brzosko et al. [3] revealed a positive correlation between CIMT with BMI and total cholesterol. The increased amount of parathrmone hormone (PTH) in the hemodialysis group is a reflection of longer duration of consuming phosphate binders and poorer control of kidney bone disease. It may partially explain the correlation between CIMT and PTH in the hemodialysis group. Dvorkova et al. [1] found an inverse relationship between CIMT and albumin, which has been previously described [0] and explained by the nutritional status of the patients in the study.

There are several studies on the association between CIMT and cardiac risk factors in patients with CKD. In these studies, CIMT was positively correlated with hypertension [1], lipid abnormalities, CRP, and PTH [2]. Dursun et al. [7] found that there were significant positive correlations between CIMT and blood pressure and CRP and significant negative correlations between CIMT and albumin, hemoglobin, and glomerular filtration rate.


  Conclusion Top


CKD is associated with increased CIMT. This suggests that even in young children uremia and/or metabolic alterations have a profound impact on the arterial structure and function leading to cardiovascular morbidity and mortality.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.[22]

 
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