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Hesham Safouh, MD Prof. of Pediatrics and Pediatric Nephrology Cairo University.

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Presentation on theme: "Hesham Safouh, MD Prof. of Pediatrics and Pediatric Nephrology Cairo University."— Presentation transcript:

1 Hesham Safouh, MD Prof. of Pediatrics and Pediatric Nephrology Cairo University

2  Widespread availability of state-of-the-art renal replacement therapy!! Safouh, MD

3  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.

4  CVD recognized as a major cause of death in children with advanced CKD. Safouh, MD

5 Leading causes of death in the general pediatric population and in children on renal replacement therapy. Mitsnefes M M JASN 2012;23: Safouh, MD

6 ≠ A child is NOT a small adult!!

7  Coronary artery disease  Cardiomyopathy-associated congestive heart failure Safouh, MD

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9  Arrhythmia (20%)  Valvular heart disease (12%)  Cardiomyopathy (9%)  Cardiac arrest (3%) USRDS 2011 Safouh, MD

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13  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. Safouh, MD

14  Elimination of uremia related risk factors  High risk for CVD from traditional risk factors. Safouh, MD

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16  Functional  Structural  Biochemical Safouh, MD

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18  Aortic pulse wave velocity  24-h ambulatory BP monitoring  Ambulatory arterial stiffness index  Heart rate variability (HRV)  Flow-mediated dilatation Safouh, MD

19  Carotid distensibility, aortic and brachioradial stiffness or loss of compliance. Safouh, MD

20 Cardiovascular risk assessment in children with chronic kidney disease Shroff et al. Pediatr Nephrol Oct, 2012 Safouh, MD

21  Demonstrates impaired LV filling early in the progression of pediatric CKD. Safouh, MD

22  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

23  HRV is an important predictor of parasympathetic / sympathetic balance.  An increase in sympathetic tone becomes a predictor of sudden cardiac death, potentially through arrhythmias. Safouh, MD

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26  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

27  FMD and FMD/NTG-MD ratio were significantly lower in patients than in controls (p = and p = 0.01, respectively).  FMD correlated positively with serum calcium and negatively with alkaline phosphatase. Safouh, MD

28  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

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30  LVH  Carotid intima-media thickness  Coronary artery calcification score Safouh, MD

31 LVH IS THE MOST COMMON CARDIAC ABNORMALITY IN CHILDREN WITH CKD Safouh, MD

32  Measures the presence, type, and degree of left ventricular hypertrophy (LVH) Safouh, MD

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34  Measures carotid artery intima media thickness (cIMT), indicating structural changes in the arterial tree Safouh, MD

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36 Normal values of carotid intima-media thickness (cIMT) in healthy adolescents. Cardiovascular risk assessment in children with chronic kidney disease Shroff et al. Pediatr Nephrol Oct, 2012

37 Safouh, MD

38  36 pediatric renal transplant recipients, at the end of their 1 st post - transplantation year  30 patients with ESRD on regular hemodialysis  30 normal subjects Safouh, MD

39  Doppler ultrasound for :  Carotid artery intima media thickness  Renal resistivity indices  Brachial artery flow mediated dilatation Safouh, MD

40  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) Safouh, MD

41  RRIs in the transplantation group were significantly higher than the control group (0.64 ± 0.06 vs ± 0.06, p=0.026). Safouh, MD

42  FMD % of the transplantation group was significantly higher than that of the dialysis group (12.01 ± 9.52 vs ± 6.78, p = 0.04). Safouh, MD

43  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. Safouh, MD

44  Currently available clinical measures are not sensitive enough to detect early stages of calcification.  Normal/negative test should be interpreted with caution. Safouh, MD

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46  Ca  PO4  PTH levels  Hemoglobin  Cholesterol, lipid parameters  Serum creatinine  Vitamin D Safouh, MD

47  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

48  They are not simply biomarkers but also mediators of CVD.  Fetuin-A  Osteoprotegerin (OPG),  Matrix γ-carboxyglutamic acid protein (MGP)  Pyrophosphate Safouh, MD

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52 Klotho The Greek Goddess of Fate, who spins the thread of life. Safouh, MD

53  Potent phosphaturic hormone.  Inhibits renal production of 1,25(OH)2D.  Independently associated with LVH.  Significantly elevated in stage 3 CKD.  Potential biomarker. Safouh, MD

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55  Potential direct protective effects of Klotho on the vasculature  Is Klotho a robust biomarker for early CKD? Safouh, MD

56 ≠ A child is NOT a small adult!!

57  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

58  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

59  Clinically important improvements in cardiac hypertrophy and function when children receive dialysis more frequently than the traditional, thrice-weekly in-center schedule Safouh, MD

60  Slowing the progression of CKD  Avoiding long-term dialysis  Preemptive transplantation Safouh, MD

61 Thanks for your attention!!


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