Early Prediction of Premature Atherosclerosis in Children with End Stage Renal Disease(ESRD) on Regular Haemodialysis, A Single Centre Experience 111


Mohamed A.El-Gamasy*

Citation: Early Prediction of Premature Atherosclerosis in Children with End Stage Renal Disease (ESRD) on Regular Haemodialysis, A Single Centre Experience. American Research Journal of Pediatrics; 1(1): 12-24.

Copyright This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Abstract:

Introduction:Chronic renal failure is associated with atherosclerosis and increased incidence of cardiovascular morbidity and mortality.

The aim of this work was to compare between children with ESRD under regular HD and healthy controls as regard serum levels of lipids as early predictors of premature atherosclerosis proven by common carotid intima-media thickness (CCA -IMT).

Methods: The present study was carried out on 45 children with ESRD on regular hemodialysis in an University hospital and 30 healthy age and sex matched children were serving as controls.All subjects were subjected to thorough history taking, clinical examination including anthropometric measurement and blood pressure measurements, routine laboratory assessments measuring complete blood picture, C-reactive protein, blood urea and serum Creatinine, lipid profile including serum levels of total cholesterol, triglycerides(TG), low density lipoprotein (LDL) and high density lipoprotein (HDL)and radiological assessment using B-mode Doppler ultrasonography to measure common carotid artery intima media thickness (CCA-IMT) to detect presence and extent of atherosclerosis.

Results: There was significant increase in serum levels of triglyceride, cholesterol and LDL and a significant decrease in HDL in dialysis children when compared to healthy controls. There was also a highly significant increase in CCA-IMT of the patients group when compared to the controls (P < 0.001) with significant positive correlation with duration of dialysis and serum TG and a significant negative correlation with serum HDL.

Conclusions: Increased serum levels of TG, cholesterol, LDL and decreased serum level of HDL are early predictors for premature atherosclerosis in children with ESRD. Keywords: Atherosclerosis, Children, Haemodialysis, Chronic Renal.


Description:

Background: Cardiovascular disease accounts for one quarter of deaths in children and adults younger than 30 years old who started treatment of end stage renal disease(ESRD) at their childhood period (1, 2). Dyslipidemia became frequent in long term survivors undergoing maintenance hemodialysis due to improvement of dialysis adequacy (3, 4, 5).

The aim of this work was to compare between children with ESRD under regular HD and healthy controls as regard serum levels of lipids as early predictors of premature atherosclerosis proven by common carotid intima-media thickness (CCA -IMT).
SUBJECTS AND METHODS

Sample Size, Design of the Study and Setting: The present study was carried out after approval from research ethical committee centre of Tanta University Hospital (TUH) and obtaining informed written consents from parents of included children, in Paediatric Nephrology Unit of Paediatric Department, Tanta University Hospital from August 2016 to August 2017 on 45 children with ESRD on regular haemodialysis (HD). Their ages ranged from 4 to 19 years with their mean 13.87±3.83. They were 27 males and 18 females. All patients were undergoing regular HD, three times per week, with each dialysis session lasting for three to four hours Thirty healthy children matched in age and sex distribution were serving as control group. Their ages ranged from 4 to 19 years with their mean13.8±3.8. They were 15 males and 15 females. Patients were dialyzed on Fresenius 4008- B dialysis machine (Germany) at blood flow rate = 2.5 x weight (kg) + 100ml/min., using polysulphane hollow fiber dialyzers suitable for the surface area of the patients (Fresenius F3 = 0.4 m2 , F4 = 0.7 m2 , F5 = 1.0 m2 and F6 = 1.2 m2 ). Bicarbonate dialysis solutions were used. All patients were receiving supportive therapy in the form of subcutaneous erythropoietin in a dose of 50 IU/Kg/session, IV iron dextran 100 mg/Kg/week, oral folic acid 1 mg/day, oral calcium 1000 mg/day, oral vitamin D (one alpha) in a dose of 0.01-0.05 µg/Kg/ day and oral antihypertensive medications for hypertensive patients.

Inclusion Criteria: All children with ESRD and treated by regular maintenance haemodialysis.

Exclusion Criteria: Familial hypertriglyceridemia, Diabetes Mellitus, Congeital Heart Disease and obesity.

All patients and controls were subjected to the following History taking including duration of dialysis, Clinical examination including anthropometric measurements in the dialysis free day and blood pressure measurements,

Anthropometric measurements (weight, height and midarm circumference (MAC) by CDC growth charts developed by the National Center for Health Statistics in collaboration with the National Center for Chronic Disease Pretension and Health.

Promotion (6) They were expressed as percent of ideal for age.Ideal measurement is defined as the 50th percentile for age.

Arterial blood pressure was measured by the auscultatory method using a mercury sphygmomanometer with the patient in the semi setting position after 10 minutes of rest, in the non-fistula arm using an appropriate sized cuff. Arterial blood pressure was taken as the mean value of 3 successive readings in 3 different days. The mean arterial blood pressure was measured using the following equation:

Mean arterial BP=Diastolic BP + 1/3 Pulse pressure

While, the pulse pressure equals systolic BP – diastolic BP (7)

The laboratory investigations done just predialysis and sent directly to the laboratory including haemoglobin level and serum creatinine, serum albumin, C reactive protein (CRP), Serum cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL)(6, 7, 8).

The radiological assessments included measurement of Common Carotid Artery Intima-Media thickness (CCA-IMT).

VALIDITY OF CCA-IMT MEASUREMENT

CCA-IMT measured by well trained diagnostic radiologist in department of Diagnostic Radiology of TUH by Doppler high resolution B-mode ultrasonography (US), using (Siemens Sono–Line G60F, Germany with transducer frequency 5-10 MHz linear probe for carotid arteries). CCA-IMT indicated the structural changes in arterial tree. CCA- IMT was measured on the far wall at 4 cm segment preceding the carotid bifurcation. The median Measurements of a CCA- IMT were always performed in plaque-free arterial segments in CCA.

Arteries were scanned longitudinally and transversely to determine the presence of plaques. A localized echostructure encroaching into the vessel lumen was considered to be plaque when the arterial wall was > 50% thicker than the neighbouring sites. Highly echogenic plaques producing bright white echoes with shadowing were considered to be calcifications[9 & 10]. Arterial calcifications in each arterial region were quantified qualitatively as absent (0) or present (1). The final overall score was obtained by the addition of calcifications from all studied zones. The final score ranged from 0 (absence of calcium deposits), to 3 (calcifications present in all arterial segments examined) (11). Assessment of arterial stiffeness index by measurement of CCA diameter and CCA intima-media thickness(IMT): measured by high resolution B-mode ultrasonography (Siemens Sono-Line G60F, Germany, using 5-10 MHz transducer) enabling assessment of arterial wall displacement during the cardiac cycle which was measured on the far wall at the same level as the diameter measurements and were always performed in plaque-free arterial segments in CCA (11) Statistical Analysis

Statistical analysis was performed with Statistical Package for Social Science (SPSS version 17). For quantitative data, the mean and the standard deviation were calculated, Chi-square was done for qualitative data, comparison between the

Studied groups was performed with student t-test, with P<0.05 were considered statistically significant. Correlation between variables was evaluated using Pearson’s correlation coefficient (12).

THE RESULTS

Table (1) summarize demographic data of the studied patients and controls. The decline in anthropometric measures of studied patients that there was significant growth retardation in children with ESRD as compared to controls (mean value of weight 30.1+10.1 kg versus 52.03+14.3 kg)( p<0.001) and mean value of height 131+15.01 cm versus 153.1+16.14 cm)(p<0.001) and mean value of MAC 17.46+3.71 CM versus 22.73+3.55 cm)(p<0.001). There was a significant increase in both systolic and diastolic blood pressure values in patients group compared to the controls (mean value of systolic blood pressure 139+10.04 mmHg versus 114+7.59 mmHg)(p<0.001) and mean value of diastolic blood pressure 95.5+7.42 mmHg versus 74+5.98 mmHg) (p<0.001) Table (2) summarize routine laboratory data of the studied patients and controls. There was a highly significant decrease in serum albumin and haemoglobin level in patients as compared to the controls (mean value of albumin 3.94+0.27 gm/dl versus 5.11+0.59 gm/l)(p<0.001) and mean value of HB 8.11+1.99g/dl versus 12.2+0.65 g/dl)(p<0.001)(P=0.001). There was highly significant increase in CRP in patients as compared to the controls (mean value 37.5+7.52 mg/l versus 0.7+0.08 mg/l)(p<0.001)(P=0.001). Table (3) summarize lipid panel and CCA-IMT data of the studied patients and controls. There was a highly significant increase in the serum TG and highly significant decrease in the serum HDL of the patients group when compared to the controls (mean value of serum TG 156.93+14.49 mg/dl versus 77.44+13.15 mg/dl)(p<0.001) while mean value of HDL 29.32+3.78 mg/dl versus 45.25+2.79 mg/dl)(p<0.001)(P < 0.001).

There was also statistically significant increase in serum levels of cholesterol and LDL in dialysis children (mean values were 222.06+32.26 and 150.06+22.63 mg/dl respectively) when compared to healthy controls (mean values were 159.62+29.83 and 90.39+8.8 respectively)(p<0.001). 

Regarding CCA-IMT results in our study, There was a highly significant increase in CCA-IMT of the patients group when compared to the controls (mean value 579.6+162.01 um versus 336+52.8 um)(P < 0.001). Table (4) and figures. (1-4) shows correlations between different studied parameters in patient group, Regarding CCA-IMT correlations with different studied parameters, there is significant positive correlation between the mean CCA-IMT and the dialysis duration (r= 0.291)(p=0.047). There is also significant positive correlation between CCA IMT and serum level of triglycerides (r= -0.455)(p=0.019). In contrary, there is a significant negative correlation between CCA IMT and serum level of albumin (r= -0.229 )(p=0.049) and serum level of HDL (r=-0.411)(p=0.019). In our studied patients, There is a significant negative correlation between serum level of HDL and duration of dialysis. (r= -0.339)(P=0.021). While there is a significant positive correlation between and HDL and serum level of albumin (r= 0.399)(P=0.028). And there is a significant positive correlation between serum level of triglycerides and duration of dialysis (r= 0.021)(P=0.038). While a significant negative correlation between serum level of triglycerides and serum levels of albumin (r= -0.400)(P=0.031).

No: Number
SD: Standard Deviation
MAC: Mid-Arm Circumference
t= Student t test
X2 Chi square test
P Probability
* Statistically significant
No: Number
SD: Standard Deviation
Hb: Hemoglobin
CRP: C reactive protein
t= Student t test
P Probability
* Statistically significant 
No: Number

SD: Standard Deviation

CCA-IMT: Common Carotid Artery Intima Media Thickness

HDL: High Density Lipoprotein

LDL: Law Density Lipoprotein

t Student t test

P Probability

* Statistically significant

CCA-IMT: Common Carotid Artery Intima Media Thickness

HDL: High Density Lipoprotein

r Correleation Coefficient

P Probability

* Statistically significant