| Abstract|| |
Cardiac disease is a significant cause of morbidity and mortality in children with end-stage renal disease (ESRD). The aim of this work was to study the risk factors and prevalence of cardiac diseases in Egyptian pediatric patients with ESRD under regular hemodialysis (HD). Sixty-six children with ESRD on regular HD were included and subjected to history, clinical, laboratory, chest X-rays (CXR), ECG, and two-dimensional echocardiographic study to measure different echocardiographic parameters focusing on the left ventricular ejection fraction. Ninety-two percent of the patients had a cardiovascular risk factor (62.1% hypertension, 37.9% anemia, 12.1% body mass index >95th percentile, 63% serum phosphorus >5.5 mg/dL, and 57.5% calcium-phosphorus product ≥55 mg2/dL2). A diagnosis of cardiac disease was reported in 16 (24.2%) of all studied patients, the diagnostic methods used were CXR in 39 (59 %), echocardiograms in 23 (34.8%), and electrocardiograms in 21 (31.8%), left ventricular hypertrophy/ enlargement was reported in 12 (75%) of cardiac patients, congestive heart failure/pulmonary edema in 11 (68.8%) of cardiac patients, cardiomyopathy in one (6.3%) of cardiac patients and decreased left ventricular function in one (6.3%) of cardiac patients. Ninety-two percent of patients had cardiovascular risk factors. Diagnosis of cardiac disease was reported in about a quarter of all studied patients. An echocardiography reported the left ventricular dysfunction in 12 (75%) of cardiac dialysis patients. The present study stresses the importance of echocardiography as the gold standard for the diagnosis of cardiac disease in pediatric patients under maintenance HD as a high-risk population for cardiac diseases.
|How to cite this article:|
El-Gamasy MA, Mawlana WH. Risk factors and prevalence of cardiac diseases in Egyptian pediatric patients with end-stage renal disease on regular hemodialysis. Saudi J Kidney Dis Transpl 2019;30:53-61
|How to cite this URL:|
El-Gamasy MA, Mawlana WH. Risk factors and prevalence of cardiac diseases in Egyptian pediatric patients with end-stage renal disease on regular hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Mar 23];30:53-61. Available from: http://www.sjkdt.org/text.asp?2019/30/1/53/252933
| Introduction|| |
Early prediction and management of cardiac disease as a cause of morbidity and mortality has become mandatory in the management of in children and adolescents with end-stage renal disease (ESRD).,, However, only a few publications are accessible as regards the compliance, availability, and effectiveness of the different imaging modalities which are used for early recognition of cardiac disease in children and adolescents with ESRD under regular maintenance hemodialysis (HD).,,
To improve general care for pediatric patients with maintenance HD, it is necessary to early predict risk factors and screen these patients for the possibility of cardiac disease.
| Objectives|| |
The aim of this work was to study predisposing factors and prevalence of cardiac diseases which were complicating a sample of Egyptian children diagnosed with ESRD under regular HD.
| Subjects and Methods|| |
Sample size and sampling
The sample size was 72 children to be selected. A sample frame which consists of the files of all unit attendants who fulfill the selection criteria was constructed from which the target population was chosen randomly. Only 66 children participated in this study (six patients refused to participate).
Thus, this study was carried out on 66 children and adolescents, 37 males and 29 females, with ESRD who were attending the Pediatric Nephrology Unit of Pediatric Department of Tanta University Hospital during the period from January 2017 to January 2018. Their ages ranged from 10 to 18 years with a mean value of 13.7 ± 3.9 years.
The study was conducted after approval from the research ethics committee of the Faculty of Medicine, Tanta University and informed written parental consents from the included subjects.
| Protocol of management of patients|| |
All patients were undergoing regular HD, who were started on dialysis when GFR was ≤15 mL/min/1.73 m3 three times per week, with each dialysis session lasting for 3–4 h. They were being dialyzed on Fresenius 4008-B dialysis machine (Germany) at blood flow rate = 2.5 × weight (kg) + 100 mL/min, using polysulfane 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 alphaD3) in a dose of 0.01–0.05 μg/kg/ day, and oral antihypertensive medications for hypertensive patients. The goal of pharmacologic treatment of hypertension in children is to reduce blood pressure to below the 95th percentile. Therefore, we used the term “controlled” to indicate blood pressure below the 95th percentile in response to therapy. In this study, oral magnesium therapy was given as a supportive therapy for 38 (57.6%) of our patients who had increased levels of serum phosphorus levels >5.5 mg/dL. aiming to prevent hyperparathyroidism which was considered as an important risk factor for cardiovascular disease in these patients.
All children with ESRD and treated by regular maintenance HD.
Patients with the following conditions were classified as having cardiac disease:
- Congestive heart failure (CHF), pulmonary edema (PE)
- Left ventricular hypertrophy (LVH), left ventricular enlargement (LVE)
- Decreased left ventricular (LV) function
Patients of primary cardiac diseases (e.g., congenital or rheumatic heart disease, cardiomyopathy).
All patients were subjected to:
1) Full history taking including demographic data; age (0–4, 5–9, 10–14, or 15–18 years), sex, child's previous growth and development, history about primary cause of ESRD (CAKUT, cystic kidney disease, urologie disease, congenital nephrotic syndrome, oxalosis, and Alport syndrome; acquired: glomerulonephritis, interstitial nephritis, vasculitis, chronic pyelonephritis, hypertension or others) and duration of dialysis (0–5 months, 6–11 months, 1–2.9 years, and ≥3 years) and whether there were referred by a pediatric nephrologist or general pediatrician.
2) Thorough clinical examination including: Anthropometric measurements: for the assessment of nutritional and developmental status which included:
Pre- and post-dialysis weight: which was recorded with minimal clothing using electronic weight scale in kilograms.
Height: measuring the distance from the vertex to the base of the heel in centimeters by using a stadiometer in standing position
Body mass index (BMI) percentile: (< 5%, 5%–≤85% and ≥85%). Height and (BMI; kg/m2 of height) percentiles by age and sex were calculated from tables provided by the Centers for Disease Control and Prevention. BMI was calculated by the formula:
BMI = weight (kg)/[height (m)].
Mid-arm circumference: Measurement of the circumference of the left upper arm at the midpoint between the tip of the shoulder (olecranon process) and the tip of the elbow (the acromium process) in centimeters. Vital signs: especially pre- and post-dialysis arterial blood pressure which was measured by auscultatory method using a mercury sphygmomanometer, in the semi setting position after 10 min of rest, in the nonfistula arm using an appropriately sized cuff and was taken as the mean value of three successive readings in three different days.
Hypertension was defined as systolic or diastolic blood pressure above the 95th percentile for age, height, and sex, or the use of antihypertensive medications.,
3) Routine laboratory investigation including:
Complete blood count (CBC): by an automated analyzer.
Anemia was defined as mean hemoglobin value <11 g/dL.
Blood urea, blood urea nitrogen (BUN), and serum creatinine.
Serum albumin and serum electrolytes: – (ionized calcium, potassium, and phosphorus).
Intact parathyroid hormone (PTH).
Urea reduction ratio (URR) and single-pool Kt/V values: were calculated and used as measures of dialysis adequacy.
Specimen collection and handling
Venous blood morning samples were withdrawn just before dialysis sessions. Five milliliters of them were collected using sterile needles through gentle venipuncture of puncture site under complete aseptic technique. Two milliliters which was put on 20 uL EDTA solution as anticoagulant for CBC including differential white blood cells count which was done on Leishman stained peripheral blood smear evaluated using ERMA PCE-210 N cell-counter from Erma, Inc., Japan.
4) Imaging techniques: chest X-rays (CXR), ECG and two-dimensional echocardiogram (2D-echo): They were performed in all studied patients, it showed cardiac disease in 16 only.
The parameters which were studied on 2D-echo were left ventricular ejection fraction (LVEF), left atrium/ aortic root (LA/AO) ratio, and early/late phase of ventricular filling (E/A) ratio. Left ventricular systolic function was assessed using the LVEF. LVEF >60% was considered as normal. The LA/AO ratio was measured as an indication of left atrial enlargement, values >2 being considered as abnormal. The E/A ratio, i.e., the ratio of passive filling of the ventricle, the early E wave and active filling due to atrial systole, the atrial A wave, was also determined, normal ratio ranging from 1 and 2. Diastolic dysfunction was diagnosed in patients presenting with cardiac failure and having a reversal of the E/A ratio.
Echocardiography was performed in Pediatric Nephrology and Cardiology Units of Pediatric Department of Tanta University Hospital using GE vivid 7 (GE Medical System, Horten, Norway with a 3.5-MHz multifrequency transducer). The echocardiography imaging included the two-dimensional study including E/A ratio, will be based on the average of the six regional values.
Echocardiographic imaging took place in the left lateral decubitus position. Besides the standard parasternal (long and short axis) and apical (2-and 4-chamber) images, additional apical (4-chamber) images were obtained that included the interventricular septum, the apex and the RV free wall up to tricuspid annulus. Images were digitally stored in the cine-loop format for off-line analysis. Longitudinal strain was assessed off-line, on the 4-chamber cine-loop that included the RV free wall, using speckle-tracking analysis.
| Statistical Analysis|| |
Statistical analysis was performed with Statistical Package for Social Science version 17.0 (SPSS Inc., Chicago, IL, USA). Means and standard deviations of quantitative data the studied groups were calculated and compared using the Pearson Chi-square test and Student's t-test. Value of P <0.05 was considered statistically significant. Correlation between variables was evaluated using Pearson's correlation coefficient.
| Results|| |
The demographic, clinical, laboratory, and imaging parameters of the studied patients are summarized in [Table 1]. Mean HD duration was 38 ± 43 months, and the most common dialysis duration was ≥3 years in 22 patients (33.3%). A diagnosis of the cardiac disease was reported for 16 (24.24 %) of all studied patients. LVH and/or LVE were the most common cardiac diagnoses in 12 patients (75%), followed by CHF/PE in 11 patients (68.8%), only one patient with cardiomyopathy (6.3%) and only one patient with decreased LV function (6.3%) [Table 1].
|Table 1: Demographic data, clinical signs, and diagnostic imaging results of the studied children with ESRD under HD.|
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Cardiac disease diagnosis did not differ significantly between groups defined by age, sex, primary provider (pediatric nephrologist versus general pediatrician), primary etiology of ESRD, dialysis adequacy (UUK and KT/V), or BMI percentile (P>0.05) [Table 1].
[Table 1] summarizes also parameters of mineral bone disorders as common risk factors for cardiovascular disease in dialysis patients, there was no statistically significant difference between our studied cardiac and noncardiac dialysis children as regards serum calcium, serum phosphorus, Ca × PO4 product or PTH (P >0.05). In addition, there were no statistically significant differences between cardiac and noncardiac dialysis patients as regards those with hyperphosphatemia (> 5.5 mg /dL) or those with Ca × PO4 product >55 mg2/dL (P = 0.52 and 0.8, respectively).
Cardiac disease was more frequently diagnosed in patients with hypertension than without hypertension (75 % vs. 58%, P <0.0001, [Table 1]), and in patients with anemia than without anemia (50 % vs. 34%, P = 0.0002, [Table 1]). A larger percentage of patients with cardiac disease had received dialysis for three or more years when compared to those without cardiac disease (43.8% vs. 30%, P = 0.0009).
Cardiac diagnostic procedures varied by the primary provider. However, by multivariate logistic regression analysis, higher risk of cardiac disease diagnosis was related only to hypertension [odds ratio (OR) 2.53, P = 0.0002] and anemia (OR 1.6, P = 0.0289 [Table 2].
|Table 2: Comparing between CXR, ECG, and echocardiographic parameters of the studied cardiac patients with ESRD.|
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Sixty-one (92.4%) of patients had a risk factors for cardiac diseases. They included 41 (62.1 %) hypertensive, 25 (37.9%) anemic, eight (12.1%) with BMI >95th percentile, 38 (57.6 %) with serum phosphorus >5.5 mg/dL, and 35 (53%) with calcium-phosphorus product ≥55 mg2/dL2).
Patients with anemia and hypertension were more likely to develop cardiac diseases than patients without these conditions: anemia versus no anemia (P = 0.04), and hypertension versus no hypertension (P = 0.0005).
Overall, 16 (24.4 %) of the studied patients had cardiac disease, and 12 (75%) of patients who examined by echocardiography had cardiac disease [Table 1]. Combining data on general testing and the method used for cardiac diagnosis, CXR were performed for 39 (59%) of the included patients, echocardiograms for 23 (34.8 %), and ECG for 21 (31.8%) [Table 1]. LV abnormalities were diagnosed by echocardiogram in 12 (75%) of patients, by electrocardiogram in two (12.5%), and by combined echocardiogram and electrocardiogram in two (12.5 %) [Table 3]. CHF/ PE was diagnosed by CXR in 11 (68.8%) of of cardiac patients and by echocardiogram in four (25%) [Table 3]. Of the patients, 11 (27%) underwent echocardiogram and were without a cardiac diagnosis.
|Table 3: A multivariate logistic regression analysis of patients who have cardiac disease.|
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| Discussion|| |
We have previously studied “indicators of vascular dysfunctions in children with ESRD under regular HD as Pediatric Emergency” and concluded that the main cardiovascular risk factor in ESRD children on regular HD is vascular calcifications which is associated with increased stiffness of large capacitative, elastic type arteries like the aorta and common carotid artery (CCA). The extent of arterial calcification increases mainly with the duration of dialysis and abnormalities in Ca × P product).
In this work, we studied independent variables for predicting cardiac disease prevalence were age, sex, blood pressure status, primary cause of ESRD (congenital/cystic/hereditary: dysplasia, cystic kidney disease, urologic disease, congenital nephrotic syndrome, oxalosis, and Alport syndrome; acquired: glomerulonephritis, interstitial nephritis, vasculitis, chronic pyelonephritis, and hypertension; and others), duration of dialysis (0–<6 months, 6–11 months, 1–2.9 years and ≥3 years), BMI percentile (< 5%, 5–<85% and ≥85%).
We reported in this study that CXR, ECG, and 2D echocardiography as noninvasive techniques were used for the early diagnosis of cardiac disorders in our studied patients with ESRD who was undergoing HD. CXR and ECG were often used more frequently than echo. This may be attributed to the low-economic standard of included patients. Echocardiographic assessment was preferred as it can predict early subclinical cardiac lesions even at very early stages of chronic kidney disease (CKD) (Stage 1 and 2).
Both LV hypertrophy and or LV dysfunction were considered as risk factors for cardiovascular diseases and thus mortality in adult patients with ESRD under maintenance HD., LV hypertrophy and or LV dysfunction were best evaluated by Echocardiography and not by routine clinical examination, CXR or ECG.,
It was reported that death rates which were related to heart diseases in children and adolescents with ESRD under HD was one thousand times more frequent than the general mortality rate from heart diseases in infancy and childhood.
There were no previous articles which studied guidelines for indications of diagnostic tests for pediatric cardiac diseases in patients with ESRD under HD. However, echocardiography was previously recommended in the literature since the 1980s as early diagnostic and prognostic procedure for cardiac disorders in pediatric patients with ESRD.,,
Previously published articles on pediatric studies had reported a high prevalence of abnormal LV structure and or function in their children with chronic renal failure.,,,, In an Israeli study, asymmetric septal hypertrophy was diagnosed with a criterion for hypertrophic cardiomyopathy (HC) by echocardiography in nearly half of their pediatric patients with ESRD under HD Goren et al had reported that the right and left ventricular diastolic dysfunction was recorded in all of their studied children with ESRD under HD and added neither their renal transplant children nor their 37 controls had cardiac lesions by echocardio-graphy Mitsnefes et al concluded that three-quarter of studied adolescents with ESRD under HD had severe LV hypertrophy by echocardiographic examination.
Ulinski et al reported that LV hypertrophy was reported by echocardiographic examination in about 80 % of their studied French children at the start of their HD therapy.
Chinali et al had studied one hundred and thirty pediatric patients with ages ranged from three to 18 years by standard 2D echo who were diagnosed with pre-dialysis chronic renal failure from stage 2 to stage 4 and concluded that there were five-fold increase in the prevalence of systolic dysfunction in their patients when compared with a similar number of age- and sex-matched control group. One-quarter of their patients had lower fractional shortening at the endocardial and mid wall levels in the presence of elevated arterial blood pressure increased LV mass and concentric LV hypertrophy in comparison with 5% of healthy controls and added that systolic dysfunction was associated with anemia in their patients with concentric LVH. Recent Kidney Disease Outcomes Quality Initiative clinical practice guidelines for cardiac diseases in dialysis patients recommended performing echocardiography in children once dry weight has been achieved and screening for traditional cardiovascular risk factors
In this work, we did not find any significant difference between cardiac and noncardiac dialysis patients related to serum calcium level, phosphate level, Ca × PO4 product or PTH level. Previously published articles found a high prevalence of cardiovascular risk factors in their dialysis pediatric patients, including anemia, hypertension, obesity and abnormal calcium–phosphorus metabolism.,, Our results suggest that half and three-quarters of the studied pediatric dialysis patients with hypertension and anemia respectively were diagnosed with some forms of cardiac diseases so dialysis patients with anemia and/or hypertension were recommended to undergo routine screening for cardiac diseases. Hypertension and anemia has been previously reported as common risk factors for cardiac diseases in pediatric dialysis patients.,,,,,, These data recommended that hypertension and/or anemia should be considered an indication for annual screening for cardiac diseases in pediatric patients with ESRD who underwent regular maintenance HD. In spite of the high prevalence of cardiac diseases and their risk factors in these studied patients, only 34.8% of our children underwent 2D-echo. In comparing pediatric nephrologist versus general pediatrician, we found that pediatric nephrologist had a higher incidence of requesting various diagnostic procedures for cardiac diseases. This might be attributed to increased awareness of pediatric nephrologist about the commonality of cardiac diseases in their dialysis patients.
| Limitation of the study|| |
One of the limitations of this work was small sized sample of subjects and therefore, further studies on a wider scale of children will be needed to clarify the risk factors and prevalence of cardiac diseases in children with ESRD. Another imitation was lack of uniform definitions for the diagnoses of cardiac diseases in this population. The third limitations for this study was that we did not estimate serum 25 OH Vitamin D as it its deficiency is considered as one of risk factors for cardiovascular diseases in children with ESRD undergoing HD.
| Conclusions|| |
There were a significant number of children and adolescents with ESRD under maintenance HD had some form of cardiac diseases which were more prevalent in pediatric patients with hypertension and anemia. Echocardiography was an important diagnostic procedure for their diagnosis.
| Recommendations|| |
Regular screening, early diagnosis, and follow-up of cardiac diseases and their associated risk factors should be recommended during the routine care of pediatric dialysis patients. Echocardiography is considered as the gold standard for the early diagnosis of cardiac diseases in pediatric patients with ESRD.
Conflict of interest:
| References|| |
Chavers BM, Li S, Collins AJ, Herzog CA. Cardiovascular disease in pediatric chronic dialysis patients. Kidney Int 2002;62:648-53.
Groothoff JW, Gruppen MP, Offringa M, et al. Mortality and causes of death of end-stage renal disease in children: A Dutch cohort study. Kidney Int 2002;61:621-9.
Gruppen MP, Groothoff JW, Prins M, et al. Cardiac disease in young adult patients with end-stage renal disease since childhood: A Dutch cohort study. Kidney Int 2003;63:1058-65.
Lilien MR, Groothoff JW. Cardiovascular disease in children with CKD or ESRD. Nat Rev Nephrol 2009;5:229-35.
Litwin M, Grenda R, Prokurat S, et al. Patient survival and causes of death on hemodialysis and peritoneal dialysis – single-center study. Pediatr Nephrol 2001;16:996-1001.
Parekh RS, Carroll CE, Wolfe RA, Port FK. Cardiovascular mortality in children and young adults with end-stage kidney disease. J Pediatr 2002;141:191-7.
ESRD Clinical Performance Measures Project 2002 annual report: ESRD clinical performance measures project. Am J Kidney Dis 2003;42:1-96.
Update on the 1987 task force report on high blood pressure in children and adolescents: A working group report from the National High Blood Pressure Education Program. National high blood pressure education program working group on hypertension control in children and adolescents. Pediatrics 1996;98:649-58.
Romero-Corral A, Somers VK, Sierra-Johnson J, et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes (Lond) 2008;32:959-66.
Chavers BM, Solid CA, Daniels FX, et al. Hypertension in pediatric long-term hemodialysis patients in the United States. Clin J Am Soc Nephrol 2009;4:1363-9.
KDOQI. KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis 2007; 50:471-530.
Khothari CR, editor. Research Methodology, Methods and Techniques. 2nd ed. New Delhi: New Age International; 2012. p. 95-7.
El-Gamasy MA. Indicators of vascular dysfunctions in children with end stage renal disease under regular haemodialysis as paediatric emergency. J Emerg Intern Med 2017;1:6.
Foley RN, Parfrey PS, Harnett JD, et al. Clinical and echocardiographic disease in patients starting end-stage renal disease therapy. Kidney Int 1995;47:186-92.
Harnett JD, Foley RN, Kent GM, Barre PE, Murray D, Parfrey PS. Congestive heart failure in dialysis patients: Prevalence, incidence, prognosis and risk factors. Kidney Int 1995; 47:884-90.
K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005;45:S1-153.
Palcoux JB, Palcoux MC, Jouan JP, et al. Echocardiographic patterns in infants and children with chronic renal failure. Int J Pediatr Nephrol 1982;3:311-4.
Drukker A, Urbach J, Glaser J. Hypertrophic cardiomyopathy in children with end-stage renal disease and hypertension. Proc Eur Dial Transplant Assoc 1981;18:542-7.
Goren A, Glaser J, Drukker A. Diastolic function in children and adolescents on dialysis and after kidney transplantation: An echocardiographic assessment. Pediatr Nephrol 1993;7:725-8.
Mitsnefes MM, Daniels SR, Schwartz SM, Meyer RA, Khoury P, Strife CF. Severe left ventricular hypertrophy in pediatric dialysis: Prevalence and predictors. Pediatr Nephrol 2000;14:898-902.
Ulinski T, Genty J, Viau C, Tillous-Borde I, Deschênes G. Reduction of left ventricular hypertrophy in children undergoing hemodialysis. Pediatr Nephrol 2006;21:1171-8.
Chinali M, de Simone G, Matteucci MC, et al. Reduced systolic myocardial function in children with chronic renal insufficiency. J Am Soc Nephrol 2007;18:593-8.
Chavers B, Schnaper HW. Risk factors for cardiovascular disease in children on maintenance dialysis. Adv Ren Replace Ther 2001;8: 180-90.
Civilibal M, Caliskan S, Oflaz H, et al. Traditional and “new” cardiovascular risk markers and factors in pediatric dialysis patients. Pediatr Nephrol 2007;22:1021-9.
Mitsnefes MM, Daniels SR, Schwartz SM, Khoury P, Strife CF. Changes in left ventricular mass in children and adolescents during chronic dialysis. Pediatr Nephrol 2001;16:318-23.
Mohamed A El-Gamasy
Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta City, Gharbia Governate
[Table 1], [Table 2], [Table 3]