1. Hypertension in CKD:
epidemiology, treatment targets, complications
Francesco Emma
Division of Nephrology and Dialysis
Bambino Gesù Children’s Hospital, IRCCS
Rome, Italy

2. Life expectancy, according to CKD stages (Canada)
Gansevoort et al. Lancet 2013

3. Life expectancy, according to age class CKD5 vs Tx (US)
USRDS 2005 annual report and OPTN/SRTR 2006 annual report

4. Causes of death in patients with CKD (Canada)
Gansevoort et al. Lancet 2013

5. Leading causes of death in the general pediatric population
and in children on renal replacement therapy
Mitsnefes, JASN 2012

6. Risk of CV mortality at different stages of renal failure
Dégi et al, Pediatr Transpl 2012

7. Common risk factors for CVD in children with CKD
Management of HTN in children with CKD needs to be
associated with treatment of other risk factors for CVD
Mitsnefes MM, JASN 2012

8. Therapeutic lifestyle changes in hypertensive children
 Weight reduction:
primary therapy for obesity-related hypertension
prevention of weight gain limits future increases in BP
 Regular physical activity:
improves efforts at weight management
may prevent increase in BP over time
 Dietary modification:
prehypertensive children
hypertensive children
 Family-based intervention:
improve success
Source: the 4th report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents

9. CKD children can develop metabolic syndrome!
38 children with metabolic syndrome: mean LVMI was 48.3 g/m2.7
75 children without metabolic syndrome: mean LVMI was 40.0 g/m2.7
(p = 0.0008)
Wilson et al, Ped transpl 2010
Higher risk of death
Higher risk of rejection
Hanevold et al, Pediatrics 2005

10. Hypertension is a cause, a consequence, and a symptom of CKD
Early CKD
Glomerular/interstitial
damage
Mild/Moderate CKD
Sclerosis-fibrosis
Severe CKD
Gansevoort et al. Lancet 2013
HTN

11. Atherosclerosis timeline

12. Assessing CV status in children with CKD
Advantages
Disadvantages
Office BP
Easy
White coat HTN
ABPM
Easy and reliable
Operator independent
Needs equipment
Home blood pressure
Easy and reliable
Parental involvement
cIMT
Relatively easy
Operator dependant
PWV
Early sign of CV morbidity
Special equipment
in part operator dependent
Ecocardiography
Relatively easy
In part operator dependent
Strain ecocardiography
More sensitive
Special equipment
In part operator dependent
Electron beam heart CT
Early detection of coronary
calcifications
Expensive
Irradiation

13. Target
Disease State
Desired Percentile for
Gender, Age, & Height
Uncomplicated primary HTN with
no target-organ damage
BP <95th Percentile
Chronic renal disease, diabetes,
hypertensive target-organ damage
BP <90th Percentile
Source: Escape trial and the 4th report on the diagnosis, evaluation, and treatment of high blood pressure in children and
adolescents

14. Not all children with CKD are treated!
Mitsnefes et al, JASN 2003

15. Small children are more likely to be undertreated

16. Antihypertensive medications in children
• ACE inhibitors
• angiotensin receptor blockers
• beta-blockers
• calcium channel blockers
• diuretics

17. http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.pdf

18. ACEi - ARBs

19. ACEi - ARBs
 contraindicated in pregnancy
females of childbearing age should be informed
 check serum K and creatinine levels periodically
 cough is less common in children and with newer molecules
 caution with children advanced CKD or polyuria

20. ESCAPE trial
385 children, 3 to 18 years of age, with chronic kidney disease (glomerular filtration rate
of 15 to 80 ml per minute per 1.73 m2 of body-surface area) received ramipril at a dose
of 6 mg per square meter of body surface area per day.
Patients were randomly assigned to intensified blood-pressure control (with a target 24hour mean arterial pressure below the 50th percentile) or conventional blood-pressure
control (mean arterial pressure in the 50th to 95th percentile), achieved by the addition
of antihypertensive therapy that does not target the renin–angiotensin system; patients
were followed for 5 years.
The primary end-point was the time to a decline of 50% in the glomerular filtration rate
or progression to end-stage renal disease.

21. ESCAPE trial

22. Target
Disease State
Desired Percentile for
Gender, Age, & Height
Uncomplicated primary HTN with
no target-organ damage
BP <95th Percentile
Chronic renal disease, diabetes,
hypertensive target-organ damage
BP <50th Percentile
BP <90th Percentile
Source: Escape trial and the 4th report on the diagnosis, evaluation, and treatment of high blood pressure in children and
adolescents

23. Alfa- and/or beta-blockers and CCB

24. Alfa- and/or beta-blockers and CCB
 Alfa- and/or beta-blockers
- contraindicated if asthma or overt heart failure
- heart rate is dose-limiting
- may impair athletic performance
- should not be used in insulin-dependent diabetics
 Calcium channel blockers
- extended-release nifedipine tablets must be swallowed whole.
- may cause tachycardia
- may cause or worsen edema
- may cause gingival hypertrophy (in particular with CsA)

25. Step-wise approach
 Start with a small dose
 Increase progressively to the maximal dose, if tolerated
 Add a small dose of a second drug
 Increase progressively the second medication
NB: do NOT decrease treatment when BP is normal

26. Target-organ abnormalities in childhood hypertension
 Target-organ abnormalities are commonly associated with
hypertension in children and adolescents.
 Left ventricular hypertrophy (LVH) is the most prominent evidence of
target-organ damage.
 Pediatric patients with established hypertension should have
echocardiographic assessment of left ventricular mass at diagnosis
and periodically thereafter.
 The presence of LVH is an indication to initiate or intensify
antihypertensive therapy.
Source: the 4th report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents

27. Prevalence of left ventricular hypertrophy (LVH)
in pre-dialysis patients with CKD
Reference
Tucker, NDT 1997
n=85 (adults)
Prevalence of LVH
GFR >30
16%
GFR <30
38%
Levin, Am J Kidney Dis 1999
n=318 (adults)
GFR 50-75 GFR 51-25 GFR<25 Start dialysis
29%
32%
48%
70%
Johnstone, Kidney Int 1996
n=32 (age 1.5-16.9 y)
Mean plasma creatinine: 1.85 mg/dl (0.53-8.4):
22%
Mitsnefes, Kidney Int 2004
n=33 (age 6.4-20.0 y)
GFR 20-75
21%
Matteucci, JASN 2006
N= 156 (age 3-18)
CKD 2-4
33%

28. Definition of LVH in children
Height (m)
modified from de Simone JASN 2003

29. Prevalence of LVH in children with CKD
Matteucci et al, JASN 2006

30. Strain echocardiography
Provides data on cardiac function of all three planes of the heart
(circumferential, radial and longitudinal).

31. Strain echocardiography
Abnormalities in cardiac mechanics and systolic synchronicity,
also in patients with normal traditional cardiac indices.

32. Improvement of LVH with ACEi (24 months)

33. Life-threatening LVH

34. Life-threatening LVH

35. Nephrectomy has no long-term impact on
BP and LVMI in transplanted children
Ped Nephrol 2010

36. Steroid withdrawal improves blood pressure control
after pediatric renal transplantation
NDT, 2010

37. Thank you!