The Study of the Epidemiology of Pediatric Hypertension Registry (SUPERHERO): Rationale and Methods.

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research such as small sample sizes, reliance on manual record review, and limited analytic methods that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite retrospective Registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases Diagnostic Codes, 10th Revision (ICD-10 code)-defined hypertension disorder ≥January 1, 2015 and age <19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, U.S. Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to (i) reduce CVD burden across the life course and (ii) establish gold-standard biomedical informatics methods for youth with hypertension disorders.

Blood Pressure Outcomes in NICU-Admitted Infants with Neonatal Hypertension: A Pediatric Nephrology Research Consortium Study.

OBJECTIVE: To describe the blood pressure outcomes of infants admitted to the neonatal intensive care unit (NICU) with idiopathic (nonsecondary) hypertension (HTN) who were discharged on antihypertensive therapy. STUDY DESIGN: Retrospective, multicenter study of 14 centers within the Pediatric Nephrology Research Consortium. We included all infants with a diagnosis of idiopathic HTN discharged from the NICU on antihypertensive treatment. The primary outcome was time to discontinuation of antihypertensive therapy, grouped into (≤6 months, >6 months to 1 year, and >1 year). Comparisons between groups were made with χ2 tests, Fisher's exact tests, and ANOVA. RESULTS: Data from 118 infants (66% male) were included. Calcium channel blockers were the most prescribed class of antihypertensives (56%) in the cohort. The percentages remaining on antihypertensives after NICU discharge were 60% at 6 months, 26% at 1 year, and 7% at 2 years. Antenatal steroid treatment was associated with decreased likelihood of antihypertensive therapy >1 year after discharge. CONCLUSIONS: This multicenter study reports that most infants admitted to the NICU diagnosed with idiopathic HTN will discontinue antihypertensive treatment by 2 years after NICU discharge. These data provide important insights into the outcome of neonatal HTN, but should be confirmed prospectively.

The vascular protective effect of matrix Gla protein during kidney injury.

Matrix Gla protein (MGP) is a small secreted protein and requires vitamin K dependent γ-carboxylation for its function. MGP has been identified as a local inhibitor of vascular calcification because MGP-deficient mice die due to severe arterial calcification and resulting arterial rupture. Clinical trials revealed that reduction in active MGP predicts poor prognosis in patients due to cardiovascular complications. However, recent studies showed that MGP controls angiogenesis during development. MGP-deficient mice demonstrated abnormal hypervascularization and arteriovenous malformations in kidneys and other organs. This abnormal angiogenesis is largely caused by excessive expression of vascular endothelial growth factor-A (VEGF-A) and VEGF receptor-2 (VEGFR2). However, only a few studies have investigated the roles of MGP in tissue injury. We observed mesangial cell proliferation and mild interstitial fibrosis in addition to increased capillaries in kidneys of MGP-null mice even without injury. We also created a mouse model with kidney injury and found that kidney damage greatly increases MGP expression in peritubular capillary endothelial cells and tubular epithelial cells. Finally, our study showed that impairment of MGP expression aggravates peritubular capillary rarefaction and accumulation of collagen-producing myofibroblasts following kidney injury. Peritubular capillary damage induces capillary loss as well as trans-differentiation of vascular pericytes into myofibroblasts. These results indicate that MGP has the vascular protective effect in the injured kidney. Clinical trials have already started to test the efficacy of MGP activation to repair vascular calcification in patients with chronic kidney diseases. In this "Hypothesis and Theory" article, we discuss possible mechanisms by which MGP protects against vascular damage during tissue injury based on our experimental results and previous results from other research groups.