Pediatric Hypertension and the Renin-Angiotensin SystEm (PHRASE)

Summary

Studying the causal roles of components of the renin-angiotensin-aldosterone system (including angiotensin-(1-7) (Ang-(1-7)), angiotensin-converting enzyme 2 (ACE2), Ang II, and ACE), uric acid, and klotho in pediatric hypertension and related target organ injury, including in the heart, kidneys, vasculature, and brain. Recruiting children with a new hypertension diagnosis over a 2-year period from the Hypertension and Pediatric Nephrology Clinics affiliated with Brenner Children's Hospital at Atrium Health Wake Forest Baptist and Atrium Health Levine Children's Hospital. Healthy control participants will be recruited from local general primary care practices. Collecting blood and urine samples to analyze components of the renin-angiotensin-aldosterone system (Ang-(1-7), ACE2, Ang II, ACE), uric acid, and klotho, and measuring blood pressure, heart structure and function, autonomic function, vascular function, and kidney function at baseline, year 1, and year 2. Objectives are to investigate phenotypic and treatment response variability and to causally infer if Ang-(1-7), ACE2, Ang II, ACE, uric acid, and klotho contribute to target organ injury due to hypertension.

Eligibility

INCLUSION CRITERIA: HYPERTENSION COHORT

* 7-18 years of age at time of enrollment
* Confirmed new diagnosis of primary hypertension: no identifiable secondary cause, referred to hypertension or nephrology clinic

  * Age \<13 years: BP ≥95th %ile or ≥130/80 mmHg (whichever is lower)
  * Age ≥13 years: BP ≥130/80 mmHg
* Participants and their caregivers must be willing and able to commit to completing the study assessments

EXCLUSION CRITERIA: HYPERTENSION COHORT

* \<7 years or \>18 years of age at time of enrollment
* BP confirmed as normal or in the elevated BP category based on ≥3 prior office BP measurements on separate days;

  * Age \<13 years: BP \<95th %ile or \<130/80 mmHg (whichever is lower)
  * Age ≥13 years: BP \<130/80 mmHg
* A confirmed secondary cause of hypertension
* Confounding medical condition (heart or kidney disease \[except hypertension-associated heart changes on echocardiogram or albuminuria\], vascular/inflammatory disease, or diabetes)
* Inability to complete study assessments
* Non-English/Spanish speakers
* Current pregnancy
* Ward of the State

INCLUSION CRITERIA: CONTROL COHORT

* 7-18 years of age at time of enrollment
* Normal BP based on ≥3 prior office BP measurements on separate days;

  * Age \<13 years: BP \<90th %ile or \<120/80 mmHg (whichever is lower)
  * Age ≥13 years: BP \<120/80 mmHg
* Participants and their caregivers must be willing and able to commit to completing the study assessments

EXCLUSION CRITERIA: CONTROL COHORT

* \<7 or \>18 years of age at time of enrollment
* Elevated BP or hypertension, based on ≥3 prior office BP measurements on separate days:

  * Age \<13 years: BP ≥90th %ile or ≥120/80 mmHg (whichever is lower)
  * Age ≥13 years: BP ≥120/80 mmHg
* History of elevated BP or hypertension
* Current use of BP-lowering medications
* Confounding medical condition (heart or kidney disease, vascular/inflammatory disease, or diabetes)
* Inability to complete study assessments
* Non-English/Spanish speakers
* Current pregnancy
* Ward of the State

Conditions19

Locations1 site

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