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KIDNEY DISEASES
293
Original Paper
Iranian Journal of Kidney Diseases | Volume 12 | Number 5 | September 2018
Myocardial Function in Egyptian Pediatric Patients With
Acute Nephritic Syndrome
Mohamed A El-Gamasy, Walid N Elshehaby
Introduction. Acute nephritic syndrome (ANS) is the most common
cause of hypertensive heart failure in pediatric population. There are
few publications on myocardial evaluation using electrocardiographic
and echocardiographic data in pediatric patients with ANS. This
study aimed to evaluate myocardial function by electrocardiography
and 2-dimensional echocardiography in Egyptian pediatric patients
with ANS.
Materials and Methods. Sixty children with ANS were included
and subjected to clinical, laboratory, electrocardiography for
corrected QT interval, and 2-dimensional echocardiographic study
on admission, and repeated at 6 and 12 weeks to measure left
ventricular ejection fraction, left atrium-aorta ratio, and the ratio
of peak early filling (E wave) to late diastolic filling (A wave)
velocities (E/A ratio).
Results. Prolonged corrected QT interval was reported in 22
patients (36.7%), of whom 18 had hypertension. Fourteen patients
(23.3%) had left ventricular ejection fraction below 60%. The same
children also had left atrium-aorta ratios more than 2 and E/A
ratios more than 2. Left ventricular ejection fraction became within
normal values by 6 weeks in 12 patients, and 2 become normal by
3 months of follow-up. 4 of 14 children with low left ventricular
ejection fraction (28.6%) had normal arterial blood pressure. All
of the 14 children completely recovered within 3 months.
Conclusions. Myocardial dysfunction in the acute phase of ANS
was alleviated in almost all children within 12 weeks. Although
elevated blood pressure was the commonest etiology of congestive
heart failure in children with ANS, the impact of primary myocardial
functional disturbance could also be put into consideration.
IJKD 2018;12:293-8
www.ijkd.org
Department of Pediatrics,
Faculty of Medicine, Tanta
University, Tanta, Egypt
Keywords.
electrocardiography,
echocardiography, myocardial
dysfunction, child, acute
nephritic syndrome
INTRODUCTION
Acute nephritic syndrome (ANS) is defined as
a syndrome of acute onset of gross or microscopic
hematuria, proteinuria, oliguria, hypertension,
generalized edema, and azotemia.1 In Pediatric
age, the most common type is postinfectious by
group A of beta-hemolytic streptococcal infection
of the throat or skin.2 Acute poststreptococcal
glomerulonephritis (APSGN) remains a frequent
and urgent health hazard in developing Arab
countries like Egypt.3 Although the long-term
prognosis of ANS in pediatric age is favorable, it
may be associated with dangerous complications
which may result in fatal sequlae in the early
phases of the disease. Congestive heart failure
(CHF) is one of these horrible complications
that may complicate up to one-eighth to half of
patients with ANS, resulting in unfavorable even
Myocardial Function in Acute Nephritic Syndrome—El-Gamasy and Elshehaby
294 Iranian Journal of Kidney Diseases | Volume 12 | Number 5 | September 2018
fatal sequlae.4,5
The heart-related complications may be presented
in early phases of illness. Congestive heart failure
in acute kidney injury may be attributed to salt
and water retention, which results from acute
kidney injury, hypertensive pressure overload
on the left ventricle, or hyperkalemia.4 Recent
publications have reported that some patients
with ANS may be complicated by CHF in absence
of hypertension and or hyperkalemia or other
electrolytes abnormalites.4,5 In these patients,
it was supposed that primary or idiopathic
disturbances in cardiac muscles function was the
underlying etiology precipitating CHF. In spite
of the commonality of association between ANS
and CHF, there was no enough previous research
to discuss different clinical, electrocardiographic,
and echocardiographic data in pediatric patients
with ANS.4,5 This study aimed to evaluate the
myocardial function by electrocardiography and
2-dimensional (2-D) echocardiography data in
Egyptian pediatric patients with acute nephritic
syndrome and to evaluate their relationship with
clinical and laboratory findings of these patients.
MATERIALS AND METHODS
Study Design and Setting
This randomized controlled trial was carried out
during the period from February 2017 till February
2018 on 60 children with a diagnosis of APSGN
which was the commonest form of ANS. Patients
were under follow-up at the Pediatric Nephrology
and Cardiology units of Pediatric Department of
Tanta University Hospital. The study protocol
was approval by the research ethical committee
in accordance to declaration of Helsinki and
informed written or oral consents obtained from
all participants’ parents.
The inclusion criteria were children with APSGN
as the commonest form of ANS with ages ranged
between 1 year and 12 years. The exclusion criteria
were patients with preexisting cardiac diseases
including cardiomyopathy, congenital or rheumatic
heart disease, or chronic renal problems.6
Acute glomerulonephritis was defined as acute
onset of edema, oliguria, and hematuria (gross or
microscopic) with antecedent streptococcal infection
as indicated by either a history of sore throat or
pyoderma and raised antistreptolysin O titer over
200 Todd units or antideoxyribonuclease B greater
than 170 U. Patients were diagnosed to have
hypertension if their blood pressure exceeded the
95th percentile for age, sex, and height, and severe
hypertension if their blood pressure exceeded the
99th percentile.6
Study Protocol
All of the patients received salt- and potassium-
restricted diet and fluid restriction. Patients with
hypertension received a loop diuretic (furosemide).
An antihypertensive (nifedipine) was added if
arterial blood pressure was not controlled despite
these measures. All of the patients received a
single dose of benzathine penicillin. The patients
were monitored daily for weight, fluid intake and
output, blood pressure, and signs of heart failure.
All children participating in the study
were subjected to careful history taking about
demographic data, clinical course, and outcome
from case record forms; full clinical examination,
including full cardiac examination; and laboratory
investigations: which were performed on admission.
These included complete blood count, aspartate
aminotransferase and antideoxyribonuclease B titre,
serum electrolytes (sodium, potassium, calcium, and
magnesium), serum complements levels (C3 and
C4), complete urinalysis (proteinuria, hematuria,
pyuria, casts, and urinary creatinine), blood urea
nitrogen, and serum creatinine. Serum C3 was
repeated at 8 weeks.
Electrocardiography and 2-D echocardiography
were performed for all of the patients at
admission and repeated after 6 weeks, and 12
weeks, if abnormal. Corrected QT interval in
the electrocardiography was derived from the
nomogram based on Bazzet formula. Prolonged
QT interval was defined by a value greater
than 0.40 seconds. Parameters studied on
2-D-echocardiography were left ventricular ejection
fraction (LVEF), left atrium-aortic root (LA/AO)
ratio, and the ratio of peak early filling (E wave)
to late diastolic filling (A wave) velocities (E/A
ratio). Left ventricular systolic function was
assessed using the LVEF; an LVEF greater than
60% was considered normal, 30% to 60% was
considered mildly abnormal, and less than 30%
was considered markedly abnormal. The LA/AO
ratio was measured as an indication of left atrial
enlargement; values greater than 2 were considered
abnormal. The E/A ratio, ie, ratio of passive filling
Myocardial Function in Acute Nephritic Syndrome—El-Gamasy and Elshehaby
295
Iranian Journal of Kidney Diseases | Volume 12 | Number 5 | September 2018
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 heart failure and having a reversal
of the E/A ratio.7
Echocardiography was performed at Pediatric
Cardiology Unit of Pediatric Department of Tanta
University Hospital, using a GE vivid 7 (GE
Medical System, Horten, Norway with a 3.5-MHz
multifrequency transducer). The echocardiography
imaging included the 2-D study, including E/A
ratio, were based on the average of the 6 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 offline,
on the 4-chamber cine-loop that included the RV-
free wall, using speckle-tracking analysis.8
Statistical Analysis
Statistical analysis was performed using the
SPSS software (Statistical Package for the Social
Sciences, version 17.0, SPSS Inc, Chicago, IL,
USA). The mean and standard deviation values
of quantitative data of the studied groups were
calculated and compared using the Student t test.
Correlation between variables was evaluated using
the Pearson correlation coefficient.9 A P value less
than .05 was considered significant.
RESULTS
A total of 60 patients with confirmed diagnosis of
ANS were enrolled in this study. The demographic,
clinical, and laboratory parameters of the studied
patients are summarized in Table 1. The male-female
ratio was 3:2. Forty-two of 60 patients (70%) were
older than 6 years old and 18 (30%) were from 1 to 5
years of age. Forty patients (66.7%) were presented
with hypertension, 10 (22.2%) with CHF, and 4
(6.7%) with hypertensive emergency in the form of
encephalopathy. Twenty-four patients (40%) had
a preceding upper respiratory tract infection and
20 (33.4%) had a preceding skin infection. Four
of the 10 children with CHF were with normal
arterial blood pressure. All of the children had a
hypocomplementenemia C3, which returned to
normal values in 2 months’ follow-up duration.
Six children (10%) had hyponatremia and 4 (6.7%)
had hyperkalemia. All of the 60 patients received
a protocol of treatment in the form of fluid and
sodium restriction and furosemide as loop diuretic.
The 40 patients (66.7%) with hypertension also
received nifedipine as a direct arterial vasodilator.
Table 2 summarizes the results of electro-
cardiography and 2-D echocardiographic findings.
There were tachycardia relative to age in 14
patients (23.3%) and prolonged QT interval in
22 (36.7%), which returned to normal values by
1.5-month follow-up duration. Fourteen patients
(23.3%) had an LVEF ranged from 30% to 60% on
echocardiography at presentation, which returned
to normal values after 6 weeks’ follow-up duration
in 12 (20%). The remaining 2 patients had normal
ejection fraction by 3 months’ duration of follow-
up. Four of 14 patients (28.6%) with low LVEF
were with normal blood pressure. The LA/AO
Parameter Number (%)
Age, y
1 to 5 18 (30.0)
6 to 12 42 (70.0)
Sex
Male 36 (60.0)
Female 24 (40.0)
Clinical symptoms
Swelling 56 (93.3)
Oliguria 40 (66.7)
Dark colored urine 16 (26.7)
Shortness of breath 6 (10.0)
Convulsions 4 (6.7)
Headache and or epistaxis 32 (53.3)
Clinical signs
Generalized edema 60 (100.0)
Tachycardia 14 (23.3)
Hypertension 40 (66,7)
Raised jugular venous pressure 6 (10.0)
Pulmonary edema 10 (22.2)
Disturbed consciousness 4 (6.7)
Laboratory Investigations
Hematuria 56 (93.3)
Proteinuria 40 (66.7)
Azotemia 2 (3.4)
Hyponatremia 6 (10.0)
Hyperkalemia 4 (6.7)
Hypocalcemia 0
Table 1. Demographic, Clinical, and Laboratory Data of the
Studied Children With Acute Nephritic Syndrome
Myocardial Function in Acute Nephritic Syndrome—El-Gamasy and Elshehaby
296 Iranian Journal of Kidney Diseases | Volume 12 | Number 5 | September 2018
ratio was abnormal (> 2) in 14 children (23.3%),
suggestive of left atrial enlargement. The E/A ratio
was abnormal (> 2) in 14 (23.3%), suggestive of
diastolic dysfunction. None of the patients with
low LVEF had abnormal serum electrolytes.
Table 3 summarizes the relationship of the
electrocardiography and echocardiographic
parameters with the studied clinical and laboratory
data. Prolonged corrected QT interval was
reported in 22 patients (36.7%). All the children
with prolonged corrected QT had normal serum
total and ionized calcium levels. Twelve of these
patients (54.5%) had hypertension and 2 (9.1%)
had elevated serum potassium levels.
DISCUSSION
In this study, 10 of the 60 children with ANS
were presented with heart failure, of whom 14 had
a reduced LVEF at time of clinical presentation,
suggestive for reduction in left ventricular function
(LVF). These results became within normal values
in 12 children at 6 weeks. In the remaining children,
LVF returned to normal values at 3 months. Ten
out of the 14 pediatric patients had elevated arterial
blood pressure as the most possible etiology for
disturbed LVF. The remaining 4 children were
normotensive, indicating the possibility of primary
myocardial disturbed function in ANS.
A previous research was conducted by Singh
and colleagues on 34 children with APSGN.5 In
their study, CHF was present in 9 patients and 3
patients had decreased LVF on echocardiography,
out of which 2 were with normal blood pressure.
In a previously published article conducted by
Banapurmath and colleagues, 13 out of 50 patients
had CHF.4 Twelve of these patients had hypertension.
One child was with normal blood pressure and was
presumed to be having noninfective myocarditis as
proven by auscultation of muffled cardiac sounds
and low-voltage complexes on electrocardiography.
The most common cause of CHF in patients with
ANS was hypertension. However, some previously
published articles have concluded a weak correlation
between hypertension and signs of CHF.4,5
Children (%)
Parameter At Admission At 6 Weeks At 12 Weeks
Electrocardiographic findings
Normal corrected QT 38 (63.3 ) 58 (96.7 ) 60 (100)
Prolonged corrected QT (> 0.4 s) 22 (36.7 ) 2 (3.3 ) 0
Two-dimensional echocardiography
Left ventricular ejection fraction
> 60 % 46 (76.7 ) 58 (96.7) 60 (100 )
30% to 60% 14 (23.3 ) 2 (3.3 ) 0
< 30% 0 0 0
E/A ratio*
< 2 46 (76.7) 60 (100) 60 (100)
≥ 2 14 (23.3) 0 0
Left atrial-aortic ratio
< 2 46 (76.7) 60 (100) 60 (100)
≥ 2 14 (23.3) 0 0
Table 2. Electrocardiographic and Echocardiographic Parameters of the Studied Children
*E indicates early filling of ventricle-passive phase and A, active filling phase of ventricle due to atrial systole.
Parameter Prolonged Corrected QT LVEF < 60% LA/AO ratio > 2 E/A ratio > 2
Hypertension without heart failure 12 (20) 4 (6.7) 4 (6.7) 4 (6.7)
Normotensive with heart failure 4 (6.7) 4 (6.7) 4 (6.7) 4 (6.7)
Hypertension and heart failure 4 (6.7) 4 (6.7) 4 (6.7) 4 (6.7)
Hyperkalemia with hypertension and heart failure 2 (3.4) 2 (3.4) 2 (3.4) 2 (3.4)
Hypocalcemia 0 0 0 0
*LVEF indicates left ventricular ejection fraction; E, early filling of ventricle-passive phase; and A, active filling phase of ventricle due to atrial
systole.
Table 3. Relationship Between Electrocardiography and Echocardiographic Findings and Demographic, Clinical, and Laboratory Data of
the Studied Children With Acute Nephritic Syndrome*
Myocardial Function in Acute Nephritic Syndrome—El-Gamasy and Elshehaby
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Iranian Journal of Kidney Diseases | Volume 12 | Number 5 | September 2018
Moreover, cases of ANS with cardiomegaly but
without hypertension have also been reported.10
Apart from hypertension, other possible etiologies
of CHF in ANS included circulatory congestion,
hyperkalemia, administration of excessive amounts
of intravenous fluids, especially if patients were
presented with oligoanuria leading to cardiac muscle
injury.4 Gore and Saphir have observed significant
patchy areas of myocardial damage in autopsies
examination in 16 out of 160 studied children
who died after AGN.11 With regard to therapy of
ANS, they recommended cautious administration
of intravenous fluids. In studies performed by
Manhas and colleagues and Puri and colleagues,
83% and 50% of patients, respectively, with CHF
were normotensive, and they lacked evidence of
myocarditis.12,13
Kaplan and coworkers have reported temporary
vasculitic phenomena, which affect multiple organs,
including that of the central nervous system in
ANS.14 It was likely that vasculitic phenomena
involving the myocardial tissue might explain
the decreased LVF in some patients of ANS who
were normotensives.
In the present study, 36 children (60%) had
evidence of electrocardiography abnormalities,
which was within the range of 5% to 75% reported
in various previous publications.4,12,13,15 The
electrocardiography changes seen in our work were
tachycardia in 14 (23.3%) and prolonged corrected
QT interval in 22 (36.7%), 18 (30 %) of whom had
hypertension. Eight patients (13.3%) with prolonged
QT were normotensive and had decreased LVEF and
tachycardia, suggesting myocardial dysfunction.
Two patients (3.3%) with prolonged QT had
hyperkalemia. A previous study performed by
Banapurmath and coworkers found tachycardia
in 11 cases, of whom 8 had hypertension.4 In
their study, prolonged QT interval was seen in 11
children, 9 of whom had hypertension.
The other electrocardiography abnormalities
observed in the study were bradycardia, prolonged
PR interval, ST segment elevation and depression,
tall T wave, inverted T wave, U wave, low-voltage
complexes, right axis deviation, and left axis
deviation. Another study performed by Singh and
colleagues reported 19 patients out of 34 (55.9%)
with prolonged QT. Five out of these patients were
normotensive with decreased LVF, suggesting
myocardial dysfunction.5
There were many previous studies about cardiac
dysfunction and its significance in chronic kidney
diseases, but only seldom data exist regarding
involvement of heart in acute glomerular diseases.4,5
Kamisago and Hirayama studied left ventricular
hemodynamics using M-mode and pulsed Doppler
echocardiography in 18 patients with APSGN during
the acute phase.16 The results reported that in the
acute phase of APSG, left ventricular preload,
contractility, and after load were increased mainly
due to circulatory congestion. In the present work,
14 patients (23.3%) had evidence of increased LA/
AO ratio, thereby suggesting left atrial enlargement
due to circulatory congestion. Sieck and coworkers
described a 16-year-old adolescent male with
APSGN whose echocardiography showed marked
impairment of LV systolic and diastolic function
with apical thrombus. Serial echocardiographic
examinations showed improvement over 3 weeks
with treatment.17 In our work, 14 children had
reversal of the E/A ratio and decreased LVEF
on echocardiography, indicating the presence
of systolic and diastolic dysfunction. Ten out of
these 14 patients had hypertension. The remaining
4 children were within normal blood pressure
suggesting primary myocardial involvement.
The systolic and diastolic function in our patients
became within normal values by 12 weeks of
follow-up period.
One of the limitations of this study was small-
sized sample of children, and therefore, further
studies on a wider scale of children will be hoped
to clarify the possibility of effects of primary
myocardial dysfunction in the pathophysiology
and etiology of heart failure in pediatric patients
with ANS.
CONCLUSIONS
This work has reported that myocardial
functional abnormalities in electrocardiography
and echocardiography were frequent in the
acute phase of acute nephritic syndrome. These
abnormalities were reported in some children even
in the presence of normal arterial blood pressure
and normal serum sodium and potassium levels.
Elevated arterial blood pressure was the
commonest predisposing agent in etiology of
hypervolemia of circulatory system in acute
nephritic syndrome. However, fewer children
presented by CHF without elevated blood
Myocardial Function in Acute Nephritic Syndrome—El-Gamasy and Elshehaby
298 Iranian Journal of Kidney Diseases | Volume 12 | Number 5 | September 2018
pressure, thus primary or idiopathic disturbed
myocardial function might be the underlying
etiology of CHF in these patients. Children with
ANS might be presented by systolic and diastolic
myocardial dysfunction, which was proven by
echocardiographic data. The abnormalities in
electrocardiography and echocardiographic data
were temporary, meaning that they returned to
normal values in majority of children by 12 weeks’
duration of follow-up.
CONFLICT OF INTEREST
None declared.
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Correspondence to:
Mohamed A El-Gamasy, MD
Tanta University Hospital, Pediatric Department, El Giesh St,
Tanta, Gharbia, Egypt
Tel: +20 40 333 3666
E-mail: mgamsy@gmail.com
Received February 2018
Revised May 2018
Accepted May 2018
