Congenital heart disease (CHD) is the most common type of birth defect, affecting ~1% of all newborns, with 1
in 4 children requiring cardiac surgery. Children who require surgery for CHD are at an increased risk for long-
term hypertension, chronic kidney disease (CKD), end-stage renal disease, and mortality. An excess burden of
hypertension, CKD and death has also been reported in adults with CHD suggesting that pre-disease pathways
and incident kidney disease may begin in childhood and progress into adulthood. These elevated risks, along
with the dramatically improved survival of children after cardiac surgery, require urgent focus on long-term health
in the rapidly growing population of pediatric and adult patients with CHD. Improved phenotyping of the
relationship between CHD with hypertension and CKD is needed to better understand the epidemiology and risk
factors of these outcomes in CHD. The objective in this application is to recruit and retain children with CHD in
a cohort entitled the Congenital Heart disease In Children: Kidney-AssociateD Conditions with Epidemiologic
Endpoints (CHICKADEE) study. We propose enrolling 350 children 4-8 years after their first cardiac surgery for
CHD at 4 U.S. children’s hospitals. This cohort will be target enriched enrollment for hypoplastic left heart
syndrome (HLHS) and other single-ventricle cardiac lesions, as well as those with a history of severe cardiac
defects associated with the highest risk of kidney disease. In-person visits with ambulatory blood pressure
monitoring, kidney function assessment, and cardiac and kidney biomarker measurement will be conducted at
enrollment and then annually for at least 3 total visits. The specific aims are to: 1) Characterize ambulatory
hypertension, albuminuria, and CKD in children with CHD and compare to non-CHD forms of CKD using a well-
phenotyped and established external cohort of pediatric CKD. This aim will include the entire cohort, but
particularly focus on children with HLHS and their blood pressure and glomerular filtration rate trajectories. We
will also extract clinical genetic data and samples for future genetic analyses; 2) Identify perioperative factors
and clinical characteristics associated with increased risk of hypertension, albuminuria, and CKD. Retrospective
and prospective data collection will be combined to assess associations between the number of lifetime acute
kidney injury events, medication exposures, and specific echocardiographic features with increased risk of
hypertension and CKD; and, 3) Develop panels of urine and plasma glomerular, tubular, and inflammatory
biomarkers to quantify the impact of CHD on kidney health. This aim will yield a clinical panel for early detection
of kidney injury. A biorepository will be established as a resource for current and future investigations. These
studies are critical for identifying children at the highest risk for hypertension, albuminuria, and CKD. In the future,
the developed biomarker panel will be used for prompt diagnostic and therapeutic actions. The findings will also
be applied to create consensus guidelines for kidney follow-up after cardiac surgery and data to directly support
the development of novel interventions and improve long-term outcomes and quality of life for children with CHD.