Congenital heart disease (CHD) is the most common structural birth defect and represents a growing population of survivors due to improvements in surgical and perioperative care. In the United States there are approximately 2.4 million individuals with CHD, including roughly 1 million children and 1.4 million adults. As survival has improved, attention has shifted to long-term complications that affect quality of life and longevity.
Kidney disease has emerged as a substantial, under-recognized long-term complication in people with CHD. Multiple studies report increased prevalence of hypertension, chronic kidney disease (CKD), and premature mortality among individuals with CHD. In adults with CHD, hypertension prevalence has been reported as high as 47%, and risks of hypertension and CKD are increased relative to the general population. These data raise concern that adverse kidney outcomes may originate in childhood and progress over decades.
The CHICKADEE study (Congenital Heart disease In Children: Kidney-Associated Conditions with Epidemiologic Endpoints) is a multi-center prospective cohort designed to characterize the epidemiology, risk factors, and mechanisms of CKD and hypertension in children several years after CHD surgery, with particular focus on more complex CHD phenotypes.
Specific aims reported in the protocol include estimating prevalence and incidence of hypertension and kidney disease several years after cardiac surgery, identifying clinical and perioperative risk factors, and investigating mechanistic pathways through biomarker and proteomic analyses. The protocol also seeks to enable future ancillary studies through a dedicated biorepository.
This is a prospective cohort study conducted at three clinical sites. The target enrollment is 300 children between 4 and 16 years of age who are 4 to 12 years removed from their index CHD surgery. The cohort will be stratified by CHD severity and intentionally enriched for patients with more complex single-ventricle physiology, including hypoplastic left heart syndrome (HLHS).
The protocol positions the study as the first comprehensive, collaborative longitudinal assessment of kidney outcomes in pediatric CHD populations that have been excluded from many existing pediatric nephrology cohorts.
Enrollment will total 300 children across three sites, with age eligibility of 4–16 years and surgery-to-enrollment interval of 4–12 years. The cohort is to be stratified by CHD severity and enriched for single-ventricle lesions such as HLHS and other conditions that typically undergo staged palliation. The protocol does not provide additional operational details about site-level enrollment targets or specific inclusion/exclusion criteria beyond these stratification goals in the article text.
Primary outcomes described are prevalent and incident hypertension, CKD, and kidney failure occurring several years after CHD surgery. The protocol emphasizes the importance of detecting both clinic and ambulatory BP abnormalities and characterizing kidney function and albuminuria as components of CKD assessment. Exact operational definitions (for example staging thresholds for CKD or BP cutpoints used for outcome ascertainment) were not fully detailed in the protocol summary presented.
Participants will undergo standardized clinical assessments and laboratory testing to phenotype kidney health. The study will collect measures used in pediatric kidney evaluation, including assessments of albuminuria and serum-based kidney function tests. Echocardiographic characterization of cardiac anatomy and physiology will be performed to relate cardiac status to renal outcomes.
The protocol highlights prior findings of elevated albuminuria, hypertension, and CKD in post-cardiac surgery pediatric cohorts and aims to prospectively map these outcomes in a larger, multi-site sample.
Because clinic blood pressure measurements can miss masked hypertension and patterns such as loss of nocturnal dipping, the study will use ambulatory blood pressure monitoring (ABPM) as a key tool. Prior pilot data in children with CHD demonstrated ABPM abnormalities, most commonly loss of nocturnal BP dipping. Echocardiography and standardized cardiovascular phenotyping will be used alongside ABPM to evaluate links between cardiac physiology and BP patterns.
The CHICKADEE study will incorporate both targeted and untargeted proteomic approaches to discover novel biomarkers of kidney injury, repair, inflammation, and fibrosis. The protocol notes that advances in proteomics now permit measurement of more than 10,000 proteins, which may reveal mechanistic pathways and therapeutic targets.
The investigators also recognize potential genetic contributions. They reference a systematic review identifying 47 genes plausibly linking CHD to kidney disease, including 11 genes encoding ciliary proteins important for cardiac and renal development. The study will establish a biorepository to support proteomic discovery and future genetic and mechanistic analyses. Details on which genetic assays will be performed, or how genetic data will be integrated into analysis, were not fully reported in the protocol summary.
The protocol underscores a major care gap: kidney complications in children with CHD are under-recognized and under-treated. Prior cohorts report relatively low rates of pediatric nephrology referral despite substantial burdens of hypertension and CKD. Early detection and interventions—such as RAAS blockade for albuminuria and blood pressure control—may limit progression, making pediatric identification and monitoring a potential opportunity to preserve long-term kidney health.
By prospectively defining epidemiology, risk factors, and mechanisms, this study aims to inform risk stratification, early-detection strategies, and targeted interventions for kidney disease in the growing population of children surviving CHD surgery.
The article presents study design and protocol elements but does not report some operational specifics in the provided text. For example, detailed inclusion and exclusion criteria, analytic plans, statistical power or sample-size justification beyond the target n=300, specifics of CKD and hypertension definitions, and exact laboratory or genetic assays to be used were not fully described in the protocol summary. These details may be available in the full protocol or at study initiation but were not included in the source text.