The Congenital Heart Disease in Children: Kidney-Associated Conditions with Epidemiologic Endpoints (CHICKADEE) study: Study design and protocol

BACKGROUND: Congenital heart disease (CHD) is the most common structural birth defect affecting 1% of live births. With improvements in medical and surgical management, there are now more than 2 million children and adults in the United States with CHD, a number that continues to grow. Children who undergo cardiac surgery for CHD face elevated risks of hypertension, chronic kidney disease (CKD), kidney failure, and premature mortality-complications that are more prevalent in those with single ventricle physiology and increase as they get older. Although emerging evidence suggests that the excess burden of CKD observed in adults with CHD originates in childhood, these complications remain under-recognized because they are understudied in pediatric populations and represent a critical missed opportunity for evaluation and early intervention. OBJECTIVES: This multi-center prospective cohort study aims to characterize the epidemiology, risk factors, and mechanisms of CKD and hypertension in children several years after CHD surgery, with a particular focus on complex CHD conditions. METHODS: We aim to enroll 300 children, 4 to 16 years old, across three clinical sites, 4 to 12 years after their initial CHD surgery. The cohort will be stratified by CHD severity with enrichment for hypoplastic left heart syndrome and other single-ventricle defects. Primary outcomes include prevalent and incident hypertension, CKD, and kidney failure. The study will feature comprehensive phenotyping of kidney health through standardized clinical assessments, echocardiographic characterization, ambulatory blood pressure monitoring, and novel biomarker discovery using both targeted and untargeted proteomic approaches. A biorepository will be established to facilitate future ancillary studies. SIGNIFICANCE: This study addresses critical knowledge gaps in pediatric cardio-nephrology by providing the first comprehensive and collaborative longitudinal assessment of kidney outcomes in children with CHD-a population largely excluded from existing pediatric nephrology cohorts. The study aims to inform risk stratification, enable early detection strategies, and guide development of targeted interventions to preserve long-term kidney health in this vulnerable and growing population.