|ORIGINAL RESEARCH REPORT
|Year : 2018 | Volume
| Issue : 1 | Page : 55-59
Left ventricular mass, geometric patterns, and diastolic myocardial performance in children with chronic kidney disease
Igoche David Peter1, Mustafa O Asani1, Ibrahim Aliyu2, Patience N Obiagwu1
1 Department of Paediatrics, Aminu Kano Teaching Hospital, Kano, Nigeria
2 Department of Paediatrics, Bayero University Kano/Aminu Kano Teaching Hospital, Kano, Nigeria
|Date of Web Publication||23-Feb-2018|
Dr. Igoche David Peter
Department of Paediatrics, Aminu Kano Teaching Hospital, Kano
Source of Support: None, Conflict of Interest: None
Background: Excessive left ventricular mass (LVM) and diastolic dysfunction are associated with higher morbidity and mortality among patients with chronic kidney disease (CKD). Objective: The objective of the following study is to determine the prevalence of increased LVM index (LVMI), pattern of abnormal LV geometry, and diastolic dysfunction in Nigerian CKD children and to establish a relationship of these with estimated glomerular filtration rate (eGFR). Subjects and Methods: Cross-sectional comparative study of LV structure and diastolic function of 21 children with CKD age- and sex-matched and controls asymptomatic for cardiac disease. Results: The median LVMI was 62.19 (34.7) g/m2 in CKD patients compared with 52.89 (30.2) g/m2 in controls (P = 0.04). Excessive LVMI was present in 3 (14.3%) individuals compared with none (0%) of the controls P < 0.001. The prediction equation for LVMI using eGFR is: LVMI = 123.11+ (−0.48) × eGFR ml/m2/min. Abnormal LV geometry was present in 19.05% of the CKD patients and none of the controls (P = 0.04). CKD stages differed significantly with respect to the presence of abnormality with LV geometry (P = 0.04). LV diastolic dysfunction was present in 4 (19.1%) individuals (2 each had impaired relaxation and restrictive patterns) compared with 1 (4.8%) control (restrictive pattern)-P < 0.001. Children with CKD who had abnormal LV geometry had 48 times increase in the odds of having LV diastolic dysfunction when compared with those having normal LV geometry (confidence interval = 2.31–997.18, P = 0.012). Conclusion: Excessive LVM, LV hypertrophy and diastolic dysfunction are significantly more common in children with CKD compared with controls.
Keywords: Children, chronic kidney disease, diastolic dysfunction, left ventricular hypertrophy, left ventricular mass
|How to cite this article:|
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
|How to cite this URL:|
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 [serial online] 2018 [cited 2019 Sep 23];15:55-9. Available from: http://www.jcsjournal.org/text.asp?2018/15/1/55/226043
| Introduction|| |
Chronic kidney disease (CKD) is an established risk factor for the composite outcome of all-cause mortality and cardiovascular disease in the general population. Children with CKD die commonly from cardiovascular complications with left ventricular hypertrophy (LVH) being the most implicated. Increased LV mass (LVM) is associated with LVH and LV diastolic dysfunction, and these are causally related to increased morbidity and mortality in CKD. This is because myocardial capillary degeneration, myocyte apoptosis, and autophagy which are usually associated with CKD culminate in diastolic stiffness and impairs their diastolic myocardial performance.,, Children with CKD have been found to have higher LVM compared with controls., Increase in LVM is said to begin early in the course of CKD, possibly resultant of both volume and pressure overload.,
Levin et al. have demonstrated in Canadian adult CKD patients that the incidence of LVH increases with the progressive decline in renal function and that there is an inverse linear correlation between the LVM and the glomerular filtration rate. Scanty reports on the myocardial function of children with CKD have emanated from sub-Saharan Africa, where the burden of the disease is rising, and an association of estimated glomerular filtration rate (eGFR) with LVM Index (LVMI) is yet to be determined., Adiele et al. in South-East Nigeria showed LVMI was significantly higher in children with CKD compared with controls but did not establish an association with renal function. The current report aims to determine the prevalence of increased LVMI and pattern of abnormal LV geometry with diastolic dysfunction in Nigerian children with CKD and establish a relationship between these and eGFR.
| Subjects and Methods|| |
This cross-sectional comparative study involved a total of 21 children with CKD hospitalized or attending the pediatric nephrology clinic of Aminu Kano Teaching Hospital (AKTH) Kano between September 2016 and February 2017 who were consecutively enrolled into the study. CKD was defined as either kidney damage or eGFR <60 ml/min/1.73 m 2 for ≥ 3 months. Kidney damage was defined as structural or functional abnormalities of the kidney, manifested by pathologic abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies. Children who were postrenal transplant or those with any known congenital or acquired cardiac diseases were excluded. Controls with no acute or chronic illness of the same number were matched for age and gender. These controls were recruited from the pediatric outpatient department of our hospital.
Informed consent/assent was obtained from each child's parent or guardian/child as appropriate, while approval was obtained from the Ethics Committee of AKTH prior to commencement of the study.
The sample size was determined using the prevalence of LV diastolic dysfunction in CKD patients reported by Adiele et al. The minimum number (N) per group of children required for the study was calculated using the standard formula for sample size in comparative studies.
Where: “f (α, β)” =10.5 for 90% power with 5% significance (risk of type 1 error)
“P1” = 0% (0.0) is the prevalence of LV diastolic dysfunction in non-CKD controls in a study by Adiele et al.
“P2” = 37.5% (0.375) is the prevalence of LV diastolic dysfunction in CKD patients in the same previous study by Adiele et al.
n = 17.5
This was approximated to 18. However, the sample size was raised to 21 for both cases and controls to minimize standard error.
Two-dimensional, M-mode and Doppler echocardiograms were performed on all subjects and controls using Sonoscape SSI-8000 cardiac ultrasound system with 3.5 MHz and 7.5 MHz transducers for older and younger children, respectively.
End-diastolic measurements of the LV internal dimension (LVID), interventricular septal thickness (IVST), and posterior wall thickness (PWT) were all carried out according to the guidelines of the American Society of Echocardiography. LVM was calculated using the formula: Anatomic LVM  = 1.04 ([LVID + PWT + IVST]3− [LVID]3) – 13.6 g.
LVMI was calculated by dividing the LVM by the body surface area (BSA) and compared with published normal values for age and adjudged to be excessive if above the normal range for age. Relative wall thickness (RWT) was derived from
LVH was defined in absolute terms in children as LVMI ≥124.21 g/m 2 for both males and females and increased RWT was present if ≥0.45. Abnormal LV geometric types could be eccentric hypertrophy, concentric hypertrophy, or concentric remodeling; eccentric LVH presents with high LVMI and low RWT (<0.45), with dilated internal ventricular dimensions; concentric LVH presents with high LVMI and high RWT (>0.45). In this case, wall thickness is increased in the presence of normal internal ventricular diameter. Concentric LV remodeling presents with high RWT and normal LVMI.
LV diastolic function was assessed using transmitral pulsed wave Doppler flow velocities. The peak velocity (Vmax) across the mitral valve in early and late diastole corresponding to the early (E) and atrial (A) waves were measured and the E/A ratio calculated. LV diastolic dysfunction was adjudged present if the mitral valve E/A wave ratio was <1 (impaired relaxation pattern) or >2.5 (restrictive pattern).,
Study participants had their blood urea, serum electrolytes, and creatinine levels assessed. The eGFR was calculated for each of the patients using the modified Schwartz formula.
The data collected were analyzed using the statistical package for social sciences (SPSS Inc. Chicago Illinois, United States of America).
version 16. Continuous variables were tested for normality using the Shapiro–Wilks test. Student's t-test or Man–Witney 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. Level of significance was regarded as <0.05 at 95% confidence interval (CI). Multiple linear regression analysis was used to derive association between LVMI and eGFR and logistic regression analysis was used to identify the association between LVH and LV diastolic dysfunction in CKD patients.
| Results|| |
Twenty-one CKD patients aged 3–14 years who met the inclusion criteria and a control group of apparently healthy children matched for age and sex with the CKD patients were enrolled. There were 15 males and 6 females in the CKD and control group, respectively, with M:F ratio 2.5:1. Median (interquartile range) age at diagnosis of CKD was 7.50 (6.0) years. Three children (14.3%) with CKD had undergone at least 1 session of hemodialysis. The respondents' median age (interquartile range [IQR]) was 10.0 (5.0) years. Subjects did not differ significantly from controls with respect to their median (IQR) height (130.0 [21.0] cm vs. 135.0 [22.8] cm, respectively, P = 0.11) and median (IQR) weight (25.40 [6.2] cm vs. 27.40 [9.9] cm, respectively, P = 0.45).
The median (IQR) LVMI was 62.19 (34.7) g/m 2 in CKD patients compared with 52.89 (30.2) g/m 2 in controls. The difference was statistically significant (P = 0.04). Excessive LVMI was present in 3 (14.3%) subjects compared with none (0%) of the controls (P< 0.001). Subjects with increased LVMI were older and had more severe disease (2 of them had stage 5 and 1 had stage 4 CKD) than those with a normal LVMI. After elimination of insignificant covariates including BSA, height and weight, the relationship between LVMI and eGFR remained significant (r2 = 0.593, P = 0.005). Thus, about 59.3% of the variability in LVMI can be accounted for by the eGFR. The prediction equation for LVMI using eGFR is: LVMI = 123.11+ (−0.48) × eGFR ml/m 2/min.
Four (19.05%) CKD patients had abnormal LV geometry: 2 (9.52%) had eccentric LVH (aged10 and 11 years with CKD stage 4 and 5, respectively) and 1 patient (4.76%) each had concentric LVH (aged 12 ears with CKD stage 5) and concentric remodelling (aged 12 years with CKD stage 5). None (0%) of the controls had abnormal LV geometry (P = 0.04). There exist a significant difference in the occurrence of abnormal LV geometry with increasing stages of CKD [Table 1], although further analysis using adjusted odds ratios determined by logistic regression did not significantly predict the presence of abnormal LV geometry CKD stages (P > 0.05).
|Table 1: Left ventricle geometry and characteristics of patients with chronic kidney disease|
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The mean mitral valve Vmax for the early diastolic waves (E waves) was higher in CKD children (113.50 ± 20.7 cm/s) than in controls (106.30 ± 14.9 cm/s) respectively although this was not significantly so (P = 0.20). However, in late diastole during active atrial contraction, the median A wave Vmax were also significantly higher in CKD patients than in controls P = 0.003 [Table 2].
|Table 2: Mitral valve flow parameters in chronic kidney disease patients compared with controls|
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LV diastolic dysfunction was present in 4 (19.1%) subjects (2 each had impaired relaxation [Figure 1] and restrictive patterns [Figure 2]) compared with 1 (4.8%) control (restrictive pattern)-P < 0.001.
|Figure 1: Impaired relaxation pattern on pulse wave Doppler echocardiography|
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Although individuals with LV diastolic dysfunction were older than those without (median [IQR] age 11.0 [5.5] and 10.0 [5.0] years) respectively, the difference was not statistically significant (P = 0.84).
Univariate analysis using Fisher's exact test revealed that the occurrence of LV diastolic dysfunction was significantly higher among CKD patients with abnormal LV geometry compared with those with normal LV geometry (P = 0.012). Further analysis using odds ratios determined by logistic regression showed that those who had abnormal LV geometry had 48 times increase in the odds of having LV diastolic dysfunction when compared with those having normal LV geometry (CI = 2.31–997.18, P = 0.012).
| Discussion|| |
The impact of glomerular dysfunction on LV structure and diastolic function has not been previously described in children in sub-Saharan Africa even though CKD is a common cause of morbidity and mortality in the region. This study demonstrates a relationship between excessive LVMI with glomerular dysfunction. A larger median LVMI among the CKD children was found in this study compared with controls, and this is similar to findings by Adiele et al. The pathogenesis of increased LVMI in CKD is related to a host of factors including, increased systemic arterial resistance, anemia, metabolic perturbations, neurohumoral factors, cytokines, inflammation, oxidative stress, and activation of intracellular mediators by “uremia” or reduced nephron mass themselves. Since the accurate measurement of LV mass serially over time is a critical part of the evaluation of patients with CKD, we have derived a regression equation using eGFR from which echo-derived LVMI may be predicted: LVMI = 123.11+ (−0.48) × eGFR ml/m 2/min. Although cardiac magnetic resonance imaging is the gold standard for LVM evaluation, it is often impractical or too expensive for routine clinical use. Moreover, cardiac magnetic resonance imaging with contrast (gadolinium) cannot be used in subjects with moderate-to-severe CKD or end-stage renal disease due to the risks of promoting nephrogenic systemic fibrosis.
This study shows that abnormal LV geometry derived from LVMI and RWT is significantly more common in CKD patients compared with controls. Of the spectrum of abnormal LV geometry, 14.3% had LVH (concentric and eccentric) while 4.76% had concentric remodeling. Authors ,, from Cincinnati, USA, and Canada have reported a higher LVH prevalence ranging 16%–31%. It is reported that the prevalence of LVH increases with worsening CKD  hence our lower LVH prevalence may be attributable to the fact that our CKD population was skewed toward stage 1 disease which is the mildest of the CKD spectrum. LVH is the most common cardiovascular abnormality in children with CKD. The development, persistence, and severity of LVH are very strongly associated with increased mortality risk and regression of LVH with conventional hemodialysis is associated with a decreased risk of mortality. Eccentric LVH which is due to volume overload, was predominant (9.52%) in this study compared to concentric LVH (4.76%), which is due to pressure overload, agreeing with the geometric patterns reported by Adiele et al. Reports vary as regards to which form of LVH predominates in children with CKD., Although reports from the developed part of the world show predominance of concentric hypertrophy,, this may be due to the readily available and affordable chronic dialysis and ultrafiltration with resultant marked depletion in volume overload.
The study shows that LV diastolic dysfunction using pulse wave Doppler flow velocities across the mitral valve is significantly more common in CKD patients compared with controls. About 19.1% of our subjects had diastolic dysfunction, a figure much lower than the 37.5% reported by Adiele et al. Their less stringent cutoff E/A ratio of <1.2 for impaired relaxation could explain this disparity in prevalence as the present study used a cutoff <1.
LV diastolic dysfunction is common in children with CKD because of the associated excessive LVMI in these children., At the cellular level, cardiac fibrosis occurs in the setting of excessive LVMI leading to dysfunction in the relaxation phase of the cardiac cycle. We found that subjects who had abnormal LV geometry were 48 times more likely to have LV diastolic dysfunction when compared with those having normal LV geometry. The presence of LVH is important in the development of diastolic dysfunction because the physical properties of a thickened LV wall are generally believed to contribute to an increase in the passive stiffness and to a steep diastolic pressure-volume relationship leading to diastolic dysfunction.,
A longitudinal multicenter research design would have better demonstrated the natural history of LVM, LV geometric patterns and LV diastolic dysfunction in children with CKD on follow-up. The present study with acknowledgment of a small sample size has further substantiated the existence of these cardiac abnormalities in Nigerian children with CKD, thus strengthening the case for routine echocardiographic screening in these patients.
| Conclusion|| |
We fund that excessive LVM index was present in subjects with CKD and that abnormalities of LV geometry was present in CKD subjects with eccentric LVH being the commonest. Almost one of every 5 paediatric CKD subjects have LV diastolic dysfunction. These abnormalities were all significantly commoner in children with CKD when compared with their matched controls.
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Conflicts of interest
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| References|| |
Weiner DE, Tighiouart H, Amin MG, Stark PC, MacLeod B, Griffith JL, et al.
Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: A pooled analysis of community-based studies. J Am Soc Nephrol 2004;15:1307-15.
Mitsnefes MM. Cardiovascular disease in children with chronic kidney disease. J Am Soc Nephrol 2012;23:578-85.
Kardys I, Deckers JW, Stricker BH, Vletter WB, Hofman A, Witteman JC, et al
. Echocardiographic parameters and all-cause mortality: The Rotterdam study. Int J Cardiol 2009;133:198-204.
Fisher SD, Easley KA, Orav EJ, Colan SD, Kaplan S, Starc TJ, et al
. Mild dilated cardiomyopathy and increased left ventricular mass predict mortality: The prospective P2C2 HIV multicenter study. Am Heart J 2005;150:439-47.
Ritz E. Left ventricular hypertrophy in renal disease: Beyond preload and afterload. Kidney Int 2009;75:771-3.
Glassock RJ, Pecoits-Filho R, Barbareto S. Increased left ventricular mass in chronic kidney disease and end-stage renal disease: What are the implications? Dialysis & Transplantation 2010. Available from: onlinelibrary.wiley.com/doi/10.1002/dat.20391/pdf
. [Last accessed on 2017 Jun 19]. DOI: 10.1002/dat.20391.
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.
McMahon LP, Roger SD, Levin A, Slimheart Investigators Group. Development, prevention, and potential reversal of left ventricular hypertrophy in chronic kidney disease. J Am Soc Nephrol 2004;15:1640-7.
Zoccali C, Benedetto FA, Mallamaci F, Tripepi G, Giacone G, Cataliotti A, et al
. Prognostic impact of the indexation of left ventricular mass in patients undergoing dialysis. J Am Soc Nephrol 2001;12:2768-74.
Levin A, Singer J, Thompson CR, Ross H, Lewis M. Prevalent left ventricular hypertrophy in the predialysis population: Identifying opportunities for intervention. Am J Kidney Dis 1996;27:347-54.
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.
Odetunde OI, Okafor HU, Uwaezuoke SN, Ezeonwu BU, Adiele KD, Ukoha OM, et al
. Chronic kidney disease in children as seen in a tertiary hospital in Enugu, South-East, Nigeria. Niger J Clin Pract 2014;17:196-200.
] [Full text]
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-266.
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.
Spirito P, Maron BJ, Bonow RO. Noninvasive assessment of left ventricular diastolic function: Comparative analysis of Doppler echocardiographic and radionuclide angiographic techniques. J Am Coll Cardiol 1986;7:518-26.
Foppa M, Duncan BB, Rohde LE. Echocardiography-based left ventricular mass estimation. How should we define hypertrophy? Cardiovasc Ultrasound 2005;3:17.
Bu'Lock FA, Mott MG, Martin RP. Left ventricular diastolic function in children measured by Doppler echocardiography: Normal values and relation with growth. Br Heart J 1995;73:334-9.
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.
Stewart GA, Foster J, Cowan M, Rooney E, McDonagh T, Dargie HJ, et al
. Echocardiography overestimates left ventricular mass in hemodialysis patients relative to magnetic resonance imaging. Kidney Int 1999;56:2248-53.
Barberato SH, Pecoits-Filho R. Echocardiographic alterations in patients with chronic kidney failure undergoing hemodialysis. Arq Bras Cardiol 2010;94:140-6.
Weaver DJ Jr., Kimball TR, Koury PR, Mitsnefes MM. Cardiac output and associated left ventricular hypertrophy in pediatric chronic kidney disease. Pediatr Nephrol 2009;24:565-70.
Mitsnefes MM. Cardiovascular complications of pediatric chronic kidney disease. Pediatr Nephrol 2008;23:27-39.
Mitsnefes MM. Cardiovascular disease in children with chronic kidney disease. Adv Chronic Kidney Dis 2005;12:397-405.
Hüting J. Mitral valve calcification as an index of left ventricular dysfunction in patients with end-stage renal disease on peritoneal dialysis. Chest 1994;105:383-8.
Mitsnefes MM, Kimball TR, Border WL, Witt SA, Glascock BJ, Khoury PR, et al
. Impaired left ventricular diastolic function in children with chronic renal failure. Kidney Int 2004;65:1461-6.
Ix JH, Shlipak MG, Chertow GM, Ali S, Schiller NB, Whooley MA, et al
. Cystatin C, left ventricular hypertrophy, and diastolic dysfunction: Data from the heart and soul study. J Card Fail 2006;12:601-7.
Gaasch WH, Zile MR. Left ventricular diastolic dysfunction and diastolic heart failure. Annu Rev Med 2004;55:373-94.
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[Table 1], [Table 2]