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 ...