|Year : 2019 | Volume
| Issue : 3 | Page : 79-83
Left ventricular systolic dysfunction in pediatric chronic kidney disease patients
Igoche D Peter1, Ibrahim Aliyu2, Mustafa Ohikhena Asani2, Patience Ngozi Obiagwu2, Olukemi Omowumi Ige3, Fidelia Bode-Thomas3
1 Division of Paediatric Cardiology, The Limi Children's Hospital, Abuja, Nigeria
2 Department of Paediatrics, Aminu Kano Teaching Hospital, Bayero University Kano, Kano, Nigeria
3 Department of Paediatrics, Jos University Teaching Hospital, University of Jos, Jos, Nigeria
|Date of Submission||17-May-2019|
|Date of Decision||26-Jun-2019|
|Date of Acceptance||09-Jul-2019|
|Date of Web Publication||08-Nov-2019|
Dr. Igoche D Peter
Division of Paediatric Cardiology, The Limi Children's Hospital, Wuse 2, Abuja
Source of Support: None, Conflict of Interest: None
Background: Chronic kidney disease (CKD) affects multiple organs and is an established risk factor for cardiovascular disease and mortality. Impaired systolic function of the left ventricle is common in adult CKD patients. Objective: The main objective of the study is to determine the prevalence of left ventricular systolic dysfunction (LVSD) in children with CKD and its association with age, stage of disease, and history of dialysis. Subjects and Methods: This was a comparative cross-sectional descriptive study. Twenty-one children with CKD aged 3–14 years and an equal number of age- and gender-matched apparently healthy controls were recruited. Outcome Measures: LVSD was considered present when ejection fraction (EF) <50%. Results: The mean EF of 63.9% in the patients was not significantly lower than the 65.3% recorded in the controls, but LVSD was detected in 5 (24%) and none of the controls (Fisher's exact; P = 0.001). Patients with LVSD were older than those with normal left ventricular systolic function, but this difference was not statistically significant (P = 0.067); however, they differed significantly with respect to the stage of CKD (P < 0.001). LVSD was more common in patients who were never dialyzed (P < 0.001). Conclusion: LVSD is more frequent in children with CKD compared with controls. Patients with LVSD were similar to those without it, with respect to age but had more advanced disease (CKD) and less likely to have ever been dialyzed.
Keywords: Children, chronic kidney disease, ejection fraction, left ventricular systolic dysfunction
|How to cite this article:|
Peter ID, Aliyu I, Asani MO, Obiagwu PN, Ige OO, Bode-Thomas F. Left ventricular systolic dysfunction in pediatric chronic kidney disease patients. Res Cardiovasc Med 2019;8:79-83
|How to cite this URL:|
Peter ID, Aliyu I, Asani MO, Obiagwu PN, Ige OO, Bode-Thomas F. Left ventricular systolic dysfunction in pediatric chronic kidney disease patients. Res Cardiovasc Med [serial online] 2019 [cited 2020 Jan 27];8:79-83. Available from: http://www.rcvmonline.com/text.asp?2019/8/3/79/270585
| Introduction|| |
Chronic kidney disease (CKD) is a prevalent and potentially escalating disease across Sub-Saharan Africa. It is estimated that by 2030, >70% of patients with end-stage renal disease will be living in this subregion.,, Olowu et al. in 2013 based on a single-center study estimated a CKD prevalence of 48 cases/million Nigerian children. Children with CKD have the highest cardiovascular risk among the pediatric population. Left ventricular systolic dysfunction (LVSD) with progressive myocyte loss often follows LV hypertrophy occurring from pressure and volume overload in children with CKD. Chinali et al. in an European multicenter study reported that the prevalence of subclinical systolic dysfunction as defined by impaired fractional shortening (FS) was more than five-fold higher in patients with CKD compared with controls. In the same vein, Adiele et al. in Southeast Nigeria reported that ejection fraction (EF) was significantly lower in children with CKD than in controls with LVSD found in 8.3% of children with CKD versus 0% in controls. However, no clinicopathologic associations were studied. Although the occurrence of cardiovascular disease in the setting of CKD is quite common and is the leading cause of mortality in these children, this condition has received very little attention from researchers.,, We aimed to contribute to this knowledge gap in Sub-Saharan Africa by documenting the prevalence of LVSD among children with CKD, and its association with possible risk factors such as age, stage of disease, and treatment modalities such as hemodialysis. The outcome of this and similar studies should contribute to informing recommendations concerning the need or otherwise to incorporate echocardiographic screening into the routine care of children with CKD in developing countries.
| Subjects and Methods|| |
This study was carried out at the Aminu Kano Teaching Hospital (AKTH), Kano. Eligible children with CKD hospitalized or attending the pediatric nephrology clinic were recruited after due written informed parental consent and verbal assent from children aged 7 years and above.
This was a cross-sectional-comparative study.
Children with confirmed diagnosis of CKD defined by The National Kidney Foundation (NKF)/Kidney Disease and Outcome Quality Initiative as a bilateral kidney injury and/or impaired kidney function of at least 3 months' duration were recruited. Kidney injury refers to the presence of microalbuminuria or overt proteinuria or abnormal urine sediments such as red blood cell (RBC), RBC casts, white blood cell (WBC), WBC casts, cellular casts, granular casts, oval fat bodies, fatty casts, or free fats. Impaired kidney function is defined as a glomerular filtration rate (GFR) of 60 mL/min/1.73 m2 or less.
Recipients of renal transplant and children with any known congenital or acquired cardiac diseases were excluded. Controls of the same number, with no acute or chronic illness and matched for age and gender, were recruited from the pediatric outpatient department of AKTH.
Informed consent was obtained from the parents/guardians and assent from the study participants aged 7 years or older. Approval of the Ethics and Research Committee of the AKTH, Kano, was obtained before the commencement of this study.
Sample size determination
The minimum number (n) per group of children required for the study was calculated from mean ± standard deviation of EF of children with CKD and their controls as obtained from the study by Adiele et al. in Enugu, Nigeria, using the standard formula for sample size in comparison of two means. Sample size of 21 for both cases and controls was arrived at. All eligible participants were consecutively recruited to attain the sample size.
Each patient and control had a thorough physical examination performed. For the CKD patients, the stage of their disease was determined based on the estimated GFR (eGFR) as was introduced by the NKF Kidney Disease Outcomes Quality Initiative in 2002 and subsequently adopted with minor modifications by the international guideline group Kidney Disease Improving Global Outcomes in 2004.,,
A complete two-dimensional echocardiogram with M-mode examination was performed on each child using Sonoscape SSI-8000 cardiac ultrasound system with 3.2–5 MHz and 4.6–7 MHz multifrequency transducers for older and younger children, respectively. Our observations on the diastolic function of the study population have been previously reported.
LV dimensions in systole and diastole were measured according to the American Society of Echocardiography pediatric echocardiography guidelines. LV function was analyzed using the Teicholtz formula by M-mode in the parasternal short-axis view. The FS and the EF were derived from these dimensions and calculated automatically by the machine. LVSD was considered present if the FS was <28% or the EF <50%.
The study participants had their serum creatinine levels assessed, and with this, the eGFR was calculated for each patient using the modified Schwartz formula.
The data collected were analyzed using the SPSS version 22 (IBM, Armonk, NY, USA). Continuous variables were tested for normality using the Shapiro–Wilks test. Student's t-test or Mann–Whitney U-test was used to compare the means or median, respectively, of measurements between groups depending on the normality of the data. Frequencies were compared between groups using Chi-squared or Fisher's test where necessary. The relationship of EF and FS with age and eGFR was investigated using Spearman's test of correlation. Level of significance was regarded as <0.05 at 95% confidence interval.
| Results|| |
Baseline characteristics of subjects and controls
The CKD patients with their matched controls comprised 15 males and 6 females with a male-to-female ratio of 2.5:1. Their median age interquartile range (IQR) was 10.0 (5.0) years. The patients and controls were similar with respect to their height, weight, body surface area, and blood pressure [Table 1].
|Table 1: Comparison of some basic clinical parameters of chronic kidney disease patients and age- and sex-matched controls|
Click here to view
Fourteen (66.7%) CKD patients had Stage 1 disease, and 85.7% had never been dialyzed [Table 2]. The three CKD patients who had been dialyzed all received hemodialysis.
|Table 2: Basic characteristics of the children with chronic kidney disease|
Click here to view
Left ventricular dimensions
The LV internal dimensions in both phases of the cardiac cycle were larger in patients compared with controls, but these differences were not statistically significant [Table 3]. However, the interventricular septum in both phases of the cardiac cycle was significantly thicker in CKD patients. The LV posterior wall thickness in both systole and diastole were similar in the patients and controls.
|Table 3: Left ventricular dimensions and functional parameters in patients and controls|
Click here to view
Left ventricular systolic dysfunction
The mean FS (34.71% ± 8.4% vs. 35.19% ± 3.9%) and EF (63.86% ± 11.6% vs. 65.33% ± 5.4%) were reduced in the CKD patients compared with controls, but the differences were not statistically significant (P = 0.815 and P = 0.600, respectively) [Table 3]. LVSD was detected in 5 (24%) CKD patients, but in none of the controls (Fisher's exact; P = 0.001).
Patient characteristics in relation to left ventricular dysfunction
The CKD patients with LVSD were older (12 [IQR; 3.0] years) than the patients without the abnormality (9 [IQR; 6.2] years). The difference was, however, not statistically significant (P = 0.067). The occurrence of LVSD differed significantly across the stages of CKD (P < 0.001). No patient had Stage 2 CKD, but LVSD was proportionately most common in those with Stages 3 and 4 disease (50%, respectively), while 33.3% of those with Stage 5 disease had LVSD. Two of the patients (14.3%) with LVSD had Stage 1 CKD. Whereas, none of the dialyzed patients had LVSD, it was present in 27.8% those who had never been dialyzed (P < 0.001) [Table 4].
|Table 4: Patient characteristics and the presence or absence of left ventricular systolic dysfunction|
Click here to view
Spearman's test of correlation revealed a significant negative relationship between EF and age, i.e., declining EF with increasing age (r = −0.5, P = 0.02). However, no significant relationship existed between EF and eGFR (r = 0.3, P = 0.13).
| Discussion|| |
This study has confirmed that LVSD is significantly more common in children with CKD compared with healthy controls. We found a LVSD prevalence of 24%, which concurs with the 24.6% among children with CKD in an European multicenter study reported by Chinali et al. but higher than the 8.3% reported by Adiele et al. who studied children in another part of Nigeria (Enugu). Whereas, we defined LVSD in the present study as FS <28% or EF <50% the cutoff values used by Adiele et al. were not specified. They could have used a lower EF cutoff value for their definition of LVSD, which would explain the wide disparity in the prevalence observed in the two studies. We observed lower mean EF and FS in patients compared with controls, but the differences were not significant. Most other previous studies of children with CKD also reported similar observations, but all had relatively small sample sizes.,,
LVSD in patients with CKD has a complex pathobiology that is multifactorial including an increased preload secondary to fluid overload, and hypertrophy of the left ventricle which is associated with a reduction in the capillary density, creating disequilibrium between oxygen demand and supply, ultimately culminating in ischemia and myocardial fibrosis. Activation of the renin–angiotensin–aldosterone axis and sympathetic nervous system, inflammation, abnormalities of bone and mineral metabolism, and proteinuria all contribute to the pathogenesis of impaired LV systolic myocardial performance in patients with CKD.,, The severity of CKD has been noted to independently predict the elevation of LV filling pressure which is in turn responsible for systolic dysfunction in them.
We observed a significantly negative correlation between age and EF, implying that as children with CKD gets older, their LV systolic function significantly declines. It is therefore not surprising that our cohort of CKD patients with LVSD were older than those without LVSD, even though this difference was not statistically significant. It is possible, therefore, that the duration since diagnosis of CKD may be related to the decline in systolic function of the left ventricle. This might be a subject for further research.
Our finding LVSD being proportionately most common in patients with Stages 3 and 4 CKD is in consonance with the observation made by Parfrey et al. They also demonstrated that progression of renal failure frequently leads to LVSD. At Stage 5 CKD, when LVSD should be most prevalent, renal replacement therapy is usually commenced with attendant improvement in the clinical status of the patient. We had only three patients in Stage 5 CKD, all of whom had commenced hemodialysis before recruitment into this study. Larger prospective multicenter studies may more clearly delineate the variations in LV systolic function across the stages of CKD in children.
In the present study, we found a significant difference between the presence of LVSD and the dialysis status of patients. LVSD was more common among CKD patients who had never been dialyzed. Mitsnefes et al. in Cincinnati, Ohio, who studied 25 children with CKD similarly observed an improvement in their systolic performance posthemodialysis, and thus they attributed to a reduction in LV afterload. The reason for a better LV contractility in these children is not entirely clear. Probably, in this cohort of CKD patients, elevated or improved LV contractility is an adaptive mechanism needed to increase cardiac output and improve renal perfusion because of higher metabolic demands. However, Colan et al. determined that 55% of children and young adults immediately at the onset of dialysis had abnormal LV systolic function at rest. This, they hypothesized to be attributable to increase in preload or afterload.
| Conclusion|| |
In summary, we found 24% of 21 children with CKD studied in our center to have developed LVSD. This occurred irrespective of age, but was most common in CKD Stages 3 and 4, and more common in those who had never been dialyzed. Our findings suggest the need to integrate baseline and periodic echocardiography into the management protocol of children with CKD in Sub-Saharan Africa where this is not currently the standard practice in order to facilitate the early detection of LVSD and prompt intervention cardiology consultation as may be necessary. Bearing in mind a limitation of this study being a small sample size, we recommend larger multicenter studies with larger sample sizes, as this may unveil the magnitude and associations of LVSD in pediatric CKD patients in Sub-Saharan Africa.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Stanifer JW, Jing B, Tolan S, Helmke N, Mukerjee R, Naicker S, et al.
The epidemiology of chronic kidney disease in sub-Saharan Africa: A systematic review and meta-analysis. Lancet Glob Health 2014;2:e174-81.
Johnstone LM, Jones CL, Grigg LE, Wilkinson JL, Walker RG, Powell HR. Left ventricular abnormalities in children, adolescents and young adults with renal disease. Kidney Int 1996;50:998-1006.
Matteucci MC, Wühl E, Picca S, Mastrostefano A, Rinelli G, Romano C, et al.
Left ventricular geometry in children with mild to moderate chronic renal insufficiency. J Am Soc Nephrol 2006;17:218-26.
Olowu WA, Adefehinti O, Aladekomo TA. Epidemiology and clinicopathologic outcome of pediatric chronic kidney disease in Nigeria, a single cenetr study. Arab J Nephrol Transplant 2013;6:105-13.
Mitsnefes MM. Cardiovascular disease in children with chronic kidney disease. J Am Soc Nephrol 2012;23:578-85.
Parfrey PS, Harnett JD, Griffiths SM, Gault MH, Barré PE. Congestive heart failure in dialysis patients. Arch Intern Med 1988;148:1519-25.
Chinali M, de Simone G, Matteucci MC, Picca S, Mastrostefano A, Anarat A, et al.
Reduced systolic myocardial function in children with chronic renal insufficiency. J Am Soc Nephrol 2007;18:593-8.
Adiele DK, Okafor HU, Ojinnaka NC, Onwubere BJ, Odetunde OI, Uwaezuoke SN. Echocardiographic findings in children with chronic kidney disease as seen in the resource -limited setting. J Nephrol Ther 2014;4:158-61.
Price JF, Mott AR, Dickerson HA, Jefferies JL, Nelson DP, Chang AC, et al.
Worsening renal function in children hospitalized with decompensated heart failure: Evidence for a pediatric cardiorenal syndrome? Pediatr Crit Care Med 2008;9:279-84.
Olowu WA. Acute childhood cardiorenal syndrome and impact of cardiovascular morbidity on survival. Int J Nephrol 2011;2011:412495.
K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005;45:S1-153.
Kirkwood BR, Sterne JA, editors. Calculation of required sample size. In: Essential Medical Statistics. 2nd
ed. Massachusetts, USA: Blackwell Science Ltd.; 2003. p. 413-28.
Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, et al.
National kidney foundation practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Ann Intern Med 2003;139:137-47.
Levey AS, Eckardt KU, Tsukamoto Y. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005; 67:2089.
Peter ID, Asani MO, Aliyu I, Obiagwu PN. Left ventricular mass, geometric patterns, and diastolic myocardial performance in children with chronic kidney disease. J Clin Sci 2018;15:55-9. [Full text]
Lai WW, Geva T, Shirali GS, Frommelt PC, Humes RA, Brook MM, et al.
Guidelines and standards for performance of a pediatric echocardiogram: A report from the task force of the pediatric council of the American Society of Echocardiography. J Am Soc Echocardiogr 2006;19:1413-30.
Arora G, Morss AM, Piazza G, Ryan JW, Dinwoodey DL, Rofsky NM, et al.
Differences in left ventricular ejection fraction using Teichholz formula and volumetric methods by CMR: implications for patient stratification and selection of therapy. J Cardiovasc Magn Reson 2010;12 Suppl 1:P202.
Snider R. The normal echocardiographic examination. In: Snider R, Serwer G, Ritter S, editors. Echocardiography in Paediatric Heart Disease. 2nd
ed. Maryland Heights, MO.: Mosby Publishers; 1997. p. 53.
Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, et al.
New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009;20:629-37.
Mitsnefes MM, Kimball TR, Witt SA, Glascock BJ, Khoury PR, Daniels SR. Left ventricular mass and systolic performance in pediatric patients with chronic renal failure. Circulation 2003;107:864-8.
Palcoux JB, Palcoux MC, Jouan JP, Gourgand JM, Cassagnes J, Malpuech G. Echocardiographic patterns in infants and children with chronic renal failure. Int J Pediatr Nephrol 1982;3:311-4.
Nitin R, Ghodasara Malay K, Shah Harsh D. Assessment of cardiac dysfunction by 2D echocardiography in patients of chronic kidney disease. J Pharm Biomed Sci 2012;7:17-22.
Joles JA, Koomans HA. Causes and consequences of increased sympathetic activity in renal disease. Hypertension 2004;43:699-706.
Covic A, Kothawala P, Bernal M, Robbins S, Chalian A, Goldsmith D, et al.
Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of all-cause mortality, cardiovascular mortality and cardiovascular events in chronic kidney disease. Nephrol Dial Transplant 2009;24:1506-23.
McQuarrie EP, Patel RK, Mark PB, Delles C, Connell J, Dargie HJ, et al.
Association between proteinuria and left ventricular mass index: A cardiac MRI study in patients with chronic kidney disease. Nephrol Dial Transplant 2011;26:933-8.
Hung MJ, Yang NI, Wu IW, Cheng CW, Liu PC, Chen SJ, et al.
Three-dimensional echocardiographic assessment of left ventricular remodeling in predialysis chronic kidney disease patients. J Nephrol 2012;25:96-106.
Parfrey PS, Foley RN, Harnett JD, Kent GM, Murray DC, Barre PE, et al.
Outcome and risk factors for left ventricular disorders in chronic uraemia. Nephrol Dial Transplant 1996;11:1277-85.
Metivier F, Marchais SJ, Guerin AP, Pannier B, London GM. Pathophysiology of anaemia: Focus on the heart and blood vessels. Nephrol Dial Transplant 2000;15 Suppl 3:14-8.
Colan SD, Sanders SP, Ingelfinger JR. Left ventricular mechanics and contractile state in children and adolescents with end-stage renal disease: Effect of dialysis and renal transplantation. J Am Coll Cardiol 1987;10:1085-94.
[Table 1], [Table 2], [Table 3], [Table 4]