Pediatric Disorder, Pediatric Obesity, Primary Hypertension
Conditions
Keywords
Renin-Angiotensin system, Hypertension, Obesity, Angiotensin-(1-7), Angiotensin II, FGF23, Klotho, Uric acid, Left ventricular hypertrophy
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.
Interventions
None listed
Sponsors
Wake Forest University Health Sciences
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 |
| 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 |
| Albuminuria | Yearly for 3 years | Albumin-to-creatinine ratio \>30 mg/g |
| Clinic diastolic blood pressure | Yearly for 3 years | Auscultated diastolic blood pressure (mmHg) |
| 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) |
| 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) |
| Clinic systolic blood pressure | Yearly for 3 years | Auscultated systolic blood pressure (mmHg) |
Countries
United States
Outcome results
None listed