Pediatric Primary Hypertension and the Renin-Angiotensin System (PHRAS)
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Obesity Weight Loss |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology |
| Healthy: | No |
| Age Range: | 5 - 17 |
| Updated: | 12/23/2018 |
| Start Date: | December 3, 2018 |
| End Date: | December 2021 |
The Role of the Renin-Angiotensin System in Pediatric Primary Hypertension (PHRAS)
Pediatric primary hypertension is increasingly common, occurring in 5-10% of normal-weight
children and up to 25% of children with obesity. It is a risk factor for adult cardiovascular
and renal disease. But even during childhood, hypertension is associated with significant
morbidity, including cognitive impairment and organ damage. In the heart and kidneys, this
organ damage is characterized by thickened heart muscle (left ventricular hypertrophy) and
spillage of protein in the urine (albuminuria). Obese children are also at risk for fatty
liver disease. However, the cause of pediatric primary hypertension, the role of obesity, and
the mechanisms behind heart and kidney injury are poorly understood. Due to these
limitations, there are no first-line medications, and treatment is often inadequate. An
altered renin-angiotensin system may cause primary hypertension and related organ damage.
Evidence suggests uric acid, FGF23, klotho, and obesity play a role in renin-angiotensin
system-mediated injury. An improved comprehension of the pathophysiology of pediatric primary
hypertension could enhance clinical care by targeting treatment to the cause of disease and
informing novel measurement of organ damage.
children and up to 25% of children with obesity. It is a risk factor for adult cardiovascular
and renal disease. But even during childhood, hypertension is associated with significant
morbidity, including cognitive impairment and organ damage. In the heart and kidneys, this
organ damage is characterized by thickened heart muscle (left ventricular hypertrophy) and
spillage of protein in the urine (albuminuria). Obese children are also at risk for fatty
liver disease. However, the cause of pediatric primary hypertension, the role of obesity, and
the mechanisms behind heart and kidney injury are poorly understood. Due to these
limitations, there are no first-line medications, and treatment is often inadequate. An
altered renin-angiotensin system may cause primary hypertension and related organ damage.
Evidence suggests uric acid, FGF23, klotho, and obesity play a role in renin-angiotensin
system-mediated injury. An improved comprehension of the pathophysiology of pediatric primary
hypertension could enhance clinical care by targeting treatment to the cause of disease and
informing novel measurement of organ damage.
This proposal is to begin to elucidate the origins of pediatric primary hypertension and
determine how it causes cardiac and renal disease. The primary hypothesis is than an altered
renin-angiotensin system leads to the development of pediatric primary hypertension-related
organ damage in the heart and kidney, specifically left ventricular hypertrophy and
albuminuria. It is postulated that relative increase in angiotensin (Ang) ll tone compared to
Ang-(1-7) tone in the circulation and the kidney (measured in the plasma and urine,
respectively) leads to disease. The secondary hypotheses are that abnormalities in
renin-angiotensin system tone are related to higher uric acid and FGF23, lower klotho, and,
with concurrent obesity, contribute to nonalcoholic fatty liver disease. The investigators
will recruit 100 subjects aged 5-17 years who are referred for a new diagnosis of pediatric
primary hypertension to the Pediatric Nephrology clinic at Brenner Children's Hospital, 50
normotensive subjects with obesity recruited from the Brenner Families-in-Training program,
and 10 healthy normotensive from a general pediatrics clinic in the Wake Forest Baptist
Health System.
determine how it causes cardiac and renal disease. The primary hypothesis is than an altered
renin-angiotensin system leads to the development of pediatric primary hypertension-related
organ damage in the heart and kidney, specifically left ventricular hypertrophy and
albuminuria. It is postulated that relative increase in angiotensin (Ang) ll tone compared to
Ang-(1-7) tone in the circulation and the kidney (measured in the plasma and urine,
respectively) leads to disease. The secondary hypotheses are that abnormalities in
renin-angiotensin system tone are related to higher uric acid and FGF23, lower klotho, and,
with concurrent obesity, contribute to nonalcoholic fatty liver disease. The investigators
will recruit 100 subjects aged 5-17 years who are referred for a new diagnosis of pediatric
primary hypertension to the Pediatric Nephrology clinic at Brenner Children's Hospital, 50
normotensive subjects with obesity recruited from the Brenner Families-in-Training program,
and 10 healthy normotensive from a general pediatrics clinic in the Wake Forest Baptist
Health System.
Inclusion Criteria:
- Hypertension cohort: 5 to 17 years old with a new diagnosis of pediatric primary
hypertension (systolic or diastolic blood pressure >=95th percentile for
age/sex/height or >=13-/80 mmHg.
- Normotensive controls with obesity: 5 to 17 years old with normal systolic and
diastolic blood pressure (<90th percentile for age/sex/height or <120/80 mmHg) and BMI
>=85th percentile for age/sex.
- Normotensive controls: 5 to 17 years old with normal systolic and diastolic blood
pressure (<90th percentile for age/sex/height or <120/80 mmHg).
Exclusion Criteria:
- Secondary hypertension
- Confounding medical condition (e.g. diabetes mellitus, chronic kidney disease, heart
disease, vascular disease, inflammatory or rheumatologic disease)
- Non-English and non-Spanish speaking
- Inability to complete assessments
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