Hesham Safouh, MD Prof. of Pediatrics and Pediatric Nephrology Cairo University.
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Transcript of Hesham Safouh, MD Prof. of Pediatrics and Pediatric Nephrology Cairo University.
PREDICTORS OF EARLY CARDIOVASCULAR DISEASE IN CHILDREN WITH CKD
Hesham Safouh, MDProf. of Pediatrics and Pediatric NephrologyCairo University
Good news…… Widespread availability of state-of-the-art renal replacement therapy!!
Safouh, MD
Bad News…… For dialyzed children, all-cause
mortality rates have not changed significantly since the 1980s!!
Annual mortality rates per 1000 patient-years at risk, patients aged 0–19 years.
More than one decade ago…. CVD recognized as a major cause of
death in children with advanced CKD.
Safouh, MD
Leading causes of death in the general pediatric population and in children on renal replacement therapy.
Mitsnefes M M JASN 2012;23:578-585
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≠A child is NOT a small adult!!
In older adults with ESRD Coronary artery disease
Cardiomyopathy-associated congestive heart failure
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Causes of cardiac death in children
0–19 years of age with CKD
In children, causes are different……
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Arrhythmia….most common Arrhythmia (20%) Valvular heart disease (12%) Cardiomyopathy (9%) Cardiac arrest (3%)
USRDS 2011
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RISK FACTORS FOR CVD
Common risk factors for CVD in children with CKD
Common risk factors for CVD
in children with CKDSafouh, MD
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Low Birth Weight (<2500 g) LBW is associated with a reduction
in nephron number. Increased risk for obesity, type II
diabetes and CVD. LBW or prematurity has been
associated with CVD risk factors in children without kidney disease.
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Kidney transplantation Elimination of uremia related risk
factors
High risk for CVD from traditional risk factors.
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MEASURING CARDIAC AND VASCULAR
CHANGES IN CKD PATIENTS
Functional
Structural
BiochemicalSafouh, MD
Functional Studies
Functional studies Aortic pulse wave velocity 24-h ambulatory BP monitoring
Ambulatory arterial stiffness index
Heart rate variability (HRV) Flow-mediated dilatationSafouh, MD
Pulse wave velocity (PWV) Carotid distensibility, aortic and
brachioradial stiffness or loss of compliance.
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Cardiovascular risk assessment in children with chronic kidney diseaseShroff et al.Pediatr Nephrol Oct, 2012 Safouh, MD
Tissue Doppler imaging Demonstrates impaired LV filling
early in the progression of pediatric CKD.
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Multi-slice CT Endothelium-dependent and
endothelium-independent flow-mediated dilatation to demonstrate direct evidence of calcification in the coronary arteries, cardiac valves, and aortic root
Safouh, MD
The Effect of HDF on HRV in children with CKD Safouh, Essam and Attia HRV is an important predictor of
parasympathetic / sympathetic balance .
An increase in sympathetic tone becomes a predictor of sudden cardiac death, potentially through arrhythmias.
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The Effect of HDF on HRV in children with CKD Safouh, Essam and Attia
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Flow-mediated dilatation (FMD), nitro-glycerine mediated dilatation (NTG-MD) and FMD/NTG-MD ratio were estimated.
FMD was abnormal (<5%) in 24 patients (71%).
Safouh, MD
FMD and FMD/NTG-MD ratio were significantly lower in patients than in controls (p = 0.001 and p = 0.01, respectively).
FMD correlated positively with serum calcium and negatively with alkaline phosphatase. Safouh, MD
Endothelial dysfunction is present in children with CKD 4 on conservative treatment.
This may reflect increased atherogenic and thrombogenic properties of the endothelium.
Safouh, MD
Structural Changes
Structural changesLVH Carotid intima-media thickness
Coronary artery calcification score
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LVH IS THE MOST COMMON CARDIAC ABNORMALITY IN CHILDREN WITH CKD
Safouh, MD
Echocardiography Measures the presence, type, and
degree of left ventricular hypertrophy (LVH)
Safouh, MD
High-resolution ultrasound Measures carotid artery intima
media thickness (cIMT), indicating structural changes in the arterial tree
Safouh, MD
Normal values of carotid intima-media thickness (cIMT) in healthy adolescents.
Cardiovascular risk assessment in children with chronic kidney diseaseShroff et al.Pediatr Nephrol Oct, 2012
Coronary Artery Calcification Score
Safouh, MD
VASCULAR CHANGES IN PEDIATRIC RENAL TRANSPLANT RECIPIENTSSafouh, Fadel, Bazaraa, Hashem and Salah 36 pediatric renal transplant recipients,
at the end of their 1st post - transplantation year
30 patients with ESRD on regular hemodialysis
30 normal subjectsSafouh, MD
VASCULAR CHANGES IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS Methods Doppler ultrasound for :
Carotid artery intima media thickness
Renal resistivity indices Brachial artery flow mediated dilatation
Safouh, MD
Carotid artery IMT measurements in the transplantation group were significantly lower than the dialysis group (0.43 ± 0.08 mm vs. 0.5 ± 0.1 mm, p = 0.001)
VASCULAR CHANGES IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS Results
Safouh, MD
RRIs in the transplantation group were significantly higher than the control group (0.64 ± 0.06 vs. 0.61 ± 0.06, p=0.026).
VASCULAR CHANGES IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS Results
Safouh, MD
FMD % of the transplantation group was significantly higher than that of the dialysis group (12.01 ± 9.52 vs. 7.58 ± 6.78, p = 0.04) .
VASCULAR CHANGES IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS Results
Safouh, MD
IMT, RRIs and FMD % in pediatric renal transplant recipients tend to show evidence of vascular dysfunction, despite being significantly lower than those of patients on regular hemodialysis.
VASCULAR CHANGES IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS Conclusion
Safouh, MD
Not sensitive enough!! Currently available clinical measures are not sensitive enough to detect early stages of calcification.
Normal/negative test should be interpreted with caution.
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Biochemical Markers
Surrogate Markers Ca PO4 PTH levels Hemoglobin Cholesterol, lipid parameters Serum creatinine Vitamin D
Safouh, MD
Low and high levels of 1,25-(OH)-D Both are associated with high cIMT
Due to both the effects of vitamin D on calcium-phosphorus homeostasis and its pro-inflammatory properties.
Safouh, MD
Calcification inhibitors in CKD They are not simply
biomarkers but also mediators of CVD. Fetuin-A Osteoprotegerin (OPG), Matrix γ-carboxyglutamic acid
protein (MGP) PyrophosphateSafouh, MD
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KlothoThe Greek Goddess of Fate, who spins thethread of life.
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FGF-23 Potent phosphaturic hormone. Inhibits renal production of
1,25(OH)2D. Independently associated with LVH. Significantly elevated in stage 3
CKD. Potential biomarker.
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Klotho Potential direct protective
effects of Klotho on the vasculature
Is Klotho a robust biomarker for early CKD?
Safouh, MD
≠A child is NOT a small adult!!
Children have an advantage… As a population without
preexisting symptomatic cardiac disease, children with CKD potentially receive significant benefit from aggressive attempts to prevent and treat CVD.
Safouh, MD
Kt/V Unfortunately, the prescription of
adequate dialysis, as measured by Kt/V, will not necessarily decrease the risks associated with these CKD-associated complications.
Safouh, MD
More frequent dialysis Clinically important improvements in
cardiac hypertrophy and function when children receive dialysis more frequently than the traditional, thrice-weekly in-center schedule
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Best strategies…………. Slowing the progression of CKD
Avoiding long-term dialysis
Preemptive transplantation
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HESHAM SAFOUH, MDPROF. OF PEDIATRICS AND PEDIATRIC NEPHROLOGYCAIRO UNIVERSITY
Thanks for your attention!!