Hypertension in CKD: epidemiology, treatment targets, complications

Francesco Emma

Division of Nephrology and DialysisBambino Gesù Children’s Hospital, IRCCS

Rome, Italy

Gansevoort et al. Lancet 2013

Life expectancy, according to CKD stages (Canada)

USRDS 2005 annual report and OPTN/SRTR 2006 annual report

Life expectancy, according to age class CKD5 vs Tx (US)

Gansevoort et al. Lancet 2013

Causes of death in patients with CKD (Canada)

Mitsnefes, JASN 2012

Leading causes of death in the general pediatric population and in children on renal replacement therapy

Dégi et al, Pediatr Transpl 2012

Risk of CV mortality at different stages of renal failure

Common risk factors for CVD in children with CKD

Mitsnefes MM, JASN 2012

Management of HTN in children with CKD needs to be associated with treatment of other risk factors for CVD

Source: the 4th report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents

Therapeutic lifestyle changes in hypertensive children

Weight reduction:primary therapy for obesity-related hypertensionprevention of weight gain limits future increases in BP

Regular physical activity:improves efforts at weight managementmay prevent increase in BP over time

Dietary modification: prehypertensive childrenhypertensive children

Family-based intervention: improve success

Wilson et al, Ped transpl 2010

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)

Higher risk of deathHigher risk of rejection

Hanevold et al, Pediatrics 2005

Hypertension is a cause, a consequence, and a symptom of CKD

Gansevoort et al. Lancet 2013

Early CKD

Glomerular/interstitialdamage

Mild/Moderate CKD

Severe CKD

Sclerosis-fibrosis

HTN

Atherosclerosis timeline

Assessing CV status in children with CKD

Advantages Disadvantages

Office BP Easy White coat HTN

ABPM Easy and reliableOperator 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

ExpensiveIrradiation

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

Target

Source: Escape trial and the 4th report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents

Not all children with CKD are treated!

Mitsnefes et al, JASN 2003

Small children are more likely to be undertreated

• ACE inhibitors

• angiotensin receptor blockers

• beta-blockers

• calcium channel blockers

• diuretics

Antihypertensive medications in children

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

ACEi - ARBs

contraindicated in pregnancyfemales 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

ACEi - ARBs

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 24-hour 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.

ESCAPE trial

ESCAPE trial

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 PercentileBP <90th Percentile

Target

Source: Escape trial and the 4th report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents

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)

Alfa- and/or beta-blockers and CCB

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

Step-wise approach

NB: do NOT decrease treatment when BP is normal

Source: the 4th report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents

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.

Target-organ abnormalities in childhood hypertension

Reference Prevalence of LVH

Tucker, NDT 1997n=85 (adults)

GFR >30 GFR <3016% 38%

Levin, Am J Kidney Dis 1999n=318 (adults)

GFR 50-75 GFR 51-25 GFR<25 Start dialysis29% 32% 48% 70%

Johnstone, Kidney Int 1996n=32 (age 1.5-16.9 y)

Mean plasma creatinine: 1.85 mg/dl (0.53-8.4):22%

Mitsnefes, Kidney Int 2004n=33 (age 6.4-20.0 y)

GFR 20-7521%

Matteucci, JASN 2006N= 156 (age 3-18)

CKD 2-433%

Prevalence of left ventricular hypertrophy (LVH)in pre-dialysis patients with CKD

Height (m)

modified from de Simone JASN 2003

Definition of LVH in children

Matteucci et al, JASN 2006

Prevalence of LVH in children with CKD

Strain echocardiography

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

Strain echocardiography

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

Improvement of LVH with ACEi (24 months)

Life-threatening LVH

Life-threatening LVH

Ped Nephrol 2010

Nephrectomy has no long-term impact on BP and LVMI in transplanted children

NDT, 2010

Steroid withdrawal improves blood pressure control after pediatric renal transplantation

Thank you!