JOURNAL READING

Carotid Artery Function in

Children with Idiopathic
Nephrotic Syndrome
Nakysa Hooman, Roya Isa Tafreshi, Hasan Otukesh, Seyed-Hassan
Mostafavi, Farideh Hallaji (Iran University of Medical Sciences)

Muchammad Abusari (Resident of cardiology and vascular medicine)

DR .dr. Krisni Subandyah SpA(K), MKes (supervisor of pediatry,
pediatric nephrology division)
BACKGROUND
 Nephrotic patients are prone to atherosclerosis  frequent
exposure to hyperlipidemia, hypertension and
immunosuppresive drugs.
 Carotid intima-media thickness (cIMT) is an indirect marker
of atherosclerosis and target organ damage in adults
 Its value in children is still under debate but there are
increasing numbers of studies among children with risk factor
for vascular damage.
 Impaired function of endhotelium has been shown in acute
phase of idiopathic nephrotic syndrome.
 Nephrotic patients are prone to myocardial infarction and
coronary artery disease secondary to hypoalbuminemia,
dyslipidemia and hyppercoagulable state.
METHODS
 Between 2008 and 2011 all children with history of idiopathic
nephrotic syndrome
1. Idipathic nephrotic syndrome with normal serum
complement
2. Being on theraphy (continous or interrupted) for at least one
year
3. GFR > 20 ml/min/1.73m2
4. Age above two years at the time of study
5. Absence of acute infection in previous three months
6. Absence of severe edema at the time of investigation
 79 Healthy children as the control
METHODS
 Steroid response was defined as to achieve complete
remission after four weeks of steroid therapy
 The lack of remission despite of one month steroid therapy
and three consecutive pulses of methylprednisolon
considered as steroid resistant
 Two subsequent relapses during steroid therapy or within
two weeks after discontinuation of therapy or within two
weeks after discontinuation of therapy categorized as steroid
dependent.
METHODS
 cIMT is defined as the distance between the first (lumen-
intima interface) and the second (media-adventitia)
echogenic line of the far wall.
 The point 10-20 mm proximal to the common carotid
bifurcation at a 10 mm distance of far wall, at systolic phase
of cardiac contraction (maximum diameter of the common
carotid artery lumen), in mid longitudinal plane using
maximum acceptable magnification of the image ofthe far
wall.
 The internal diameter of CCA was also measured at the
same time site at both systolic (maximum diameter) and
diastolic (minimum diameter)
 The radiologist was not aware of the clinnical data of the
patients or control group.
 All measurements were carried out by one examiner who
was blinded to the status of the subjects
RESULTS
 There was correlation between LVH and carotid stiffness,
nephrotic group, proteinuria and systolic hypertension
 Multivariate analysis revealed LVMI was affected mainly by
hypertension.
Discussion
 Carotid intima –media thickness and WCSA were significantly
thicker in nephrotic patients.
 cIMT In nephrotic children was mainly correlated with duration
of disease.
 Leno C et al reported on extensive myocardial infarction in a 7
year old with minimal change nephrotic syndrome and resitant
with steroid (angiography confirmed the pesence of
atherosclerotic plaque in right coronary artery and circumflex
artery)
 Multifactorial reveals strong strong correlation between cIMT
and the rate reccurence of the disease
 The thicker cIMT was correlated with severity of proteinuria
that reflected the effects of tissue edema.
 Effective stiffness was significantly higher in hypertensive
subjects
 We found a correlation between carotid stiffness or
distensibility and high blood pressure
 There is a meta analysis revealing the beneficial effect of
usage of antihipertensive on cIMT.
 There was no correlation between cIMT and treatment with
angiotensin converting enzyme inhibitors or angiotension
receptor antagonists.
 Cardiovascular disease preceded by endothelial dysfunction
and cIMT changes
 Lorenz et al found hazard risk of 1.15 for stroke and 1.18 for
MI per 0.1 mm change of carotid thickness
 In our study the mean CIMT and WCSA were thicker in
nephrotic children
 Sub group analysis found revealed the duration of the disease
and hypertension were the main variables correlated with
carotid parameters
 Our study showed that episodes that episodes of hypertension
contributed to these vascular changes and LVH
 Carotid changes occur earlier than left ventricular hypertrophy
 Hence, it can be an easy tool for early assesment of vascular
changes before end organ damage such as LVH happen.
 Previous investigation revealed the reversibility of caroti
changes therefore serial assestment of carotid parameters,
blood pressure and lipid profile are necessary in nephrotic
patients.
 It was interesting that significant number of children with
nephrotic syndrome had abnormal left ventricular mass index
and it was more frequent in those children with systolic
hypertension and had carotid stiffness
 In our study the prevalence of advanced vascular age was
significantly higher in nephrotic children
 Length of disease more than 2 years was more associated
with advanced vascular age
 It would be a major concern for adults with childhood history
of nephrotic syndrome. They might be more prone to
atherosclerosis and vascular changes
 Longer follow up even during adulthood, close observation,
change life style, modifying atherosclerosis risk factors might
be consider seriously.
CONCLUSIONS
 CIMT was thicker in nephrotic children. Carotid parameters
were correlated with hypertension and longer duration of
disease.
 LVH was more frequent in nephrotic children and correlated
with carotid stiffness and systolic hypertension
 Carotid parameters changes occured earlier than
compensatory LVH to be appeared
THANK YOU
CRITICAL APRAISAL
 Patient Intervention Comparison Outcome
• 51 pasien •- • Perbedaan • Terdapat
dengan antara perbedaan
sindroma ketebalan ketebalan
nefrotik dinding dinding
• 75 kontrol intima arteri carotis intima
tanpa karotis antara
sindroma antara pasien
nefrotik pasien dengan
dengan kontrol yang
sindroma berhubungan
nefrotik dengan
dengan lamanya
kontrol sakit
Validitas
 Recruitment :
-51 pasien sindrom nefrotik
-75 kontrol pasien sehat

 Adjustment : -

 Maintenance : -
Validitas
 Measurement :
ketebalan dinding arteri karotis intima.
Kritisi Metode Penelitian
Penelitian diatas
Sifat pengambilan data :
observasional
Jenis penelitiannya adalah
penelitian case-control
 Membandingkan ketebalan arteri
karotis intima pasien dan kontrol
Penerapan Hasil
 Kesamaan karakteristik pasien :
Subyek penelitian adalah pasien sindroma nefrotik pada
penelitian yang mempunyai karakteristik yang hampir sama
dengan pasien-pasien sindroma nefrotik di RSSA.

 Manfaat dalam terapi pasien:

Studi ini dapat menjadi panduan bagi kita untuk mencegah
keterlambatan kerusakan pembuluh darah akibat sindrom
nefrotik yang ada di RSSA.
CAROTID INTIMA -MEDIA
THICKNESS
  In 1986 italian investigators (Pignoli) reported direct
measurement of arterial wall thickness by gross and
microscopic with B mode image.
 Carotid artery is interesting because its superfisial location,
relatively stationary and runs pararel to the surface of the
neck
 typically carotid artery is classified into 3 segments (CCA,
CB, ICA)
 CCA is the easiest to examine by ultrasound

Daniel O and Michael LB. European Heart Journal 2010.31.1682-1689

Relationship with future vascular events
 In the Kuopio Ischemic Heart Disease (KIHD) in Finland
showed an increased CIMT (>1mm) at baseline was related to
a 2.2 fold increased risk of MI
 In ARIC study demonstrated that increased CIMT was
prospectively associated with increased risk of CHD with
Hazard ratio 1.13 for MI per 0.1 mm difference in CCA IMT
 In Rotterdam study in the Netherland reported the HR being
1.19 for the same measurement
 Cardiovascular Health Study (CHS) reported HR was 1.15 for
MI. There was stronger association between CIMT ICA with MI
than CCA
 Lorenz et al in meta analyses and systemic review reported
CIMT difference of 0.1 mm the future risk of MI increased by
10-15% and stroke by 13-18%
 Recently, 20 cohort studies reported increased CIMT relates to
increased cardiovascular risk.
Daniel O and Michael LB. European Heart Journal 2010.31.1682-1689