Pediatric Primary Hypertension and the Renin-Angiotensin System (PHRAS)

Active, not recruiting

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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 >=130/80 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

Primary Outcome Measures

Name	Time	Method
Left ventricular hypertrophy	Yearly for 3 years	Left ventricular hypertrophy according to elevated left ventricular mass index (\>51 g/m\^2.7 (\>8 years of age, both sexes) or \>115 g/body surface area (males) and \>95 g/body surface area (females)) on serial echocardiogram.

Secondary Outcome Measures

Name	Time	Method
Ambulatory systolic blood pressure load	Yearly for 3 years	Percent of 24-hour ambulatory systolic blood pressure above the 95th percentile (\>25% abnormal)
Ambulatory diastolic blood pressure nocturnal dipping	Yearly for 3 years	Percent of 24-hour ambulatory diastolic blood pressure that drops below the mean blood pressure overnight
Clinic diastolic blood pressure	Yearly for 3 years	Auscultated diastolic blood pressure (mmHg)
Albuminuria	Yearly for 3 years	Albumin-to-creatinine ratio \>30 mg/g
Nonalcoholic fatty liver disease	Yearly for 3 years	Fat infiltration (yes or no) as measured on liver ultrasound with elastography in subjects with overweight/obesity (BMI \>=85th percentile)
Ambulatory diastolic blood pressure load	Yearly for 3 years	Percent of 24-hour ambulatory diastolic blood pressure above the 95th percentile (\>25% abnormal)
Ambulatory systolic blood pressure nocturnal dipping	Yearly for 3 years	Percent of 24-hour ambulatory systolic blood pressure that drops below the mean blood pressure overnight
Clinic systolic blood pressure	Yearly for 3 years	Auscultated systolic blood pressure (mmHg)
Continuous systolic blood pressure	Yearly for 3 years	Systolic blood pressure measured continuously for 10 minutes (mmHg)
Continuous diastolic blood pressure	Yearly for 3 years	Diastolic blood pressure measured continuously for 10 minutes (mmHg)

Locations (1): Wake Forest Baptist Medical Center
🇺🇸
Winston-Salem, North Carolina, United States