Kidney health in VACTERL association: structural vulnerability and surveillance

Kim and Cho [1] reported the prevalence of chronic kidney disease (CKD) and its risk factors in patients with vertebral, anal, cardiac, tracheoesophageal fistula with or without atresia, renal, and limb (VACTERL) association. In their cohort, congenital anomalies of the kidney and urinary tract (CAKUT) were highly prevalent (89.4%), and 14.9% of patients developed CKD during a mean follow-up of 3.26 years. Complex kidney anomalies and severe acute kidney injury (AKI) emerged as independent risk factors for CKD progression. These findings provide important insight into kidney vulnerability in a population for whom longitudinal outcome data remain limited and kidney surveillance strategies are not well established.

The natural course of kidney function in individuals with VACTERL association has not been clearly defined. The absence of standardized surveillance recommendations reflects the scarcity of large-scale longitudinal studies. Previous studies have been limited by short follow-up periods or small sample sizes [1,2]. The relatively short follow-up duration may be insufficient to capture the long-term trajectory of CKD progression, thereby limiting the ability to perform robust longitudinal analyses. In addition, prior reports, including the index study, are based on retrospective designs, which introduce potential selection bias and limit the ability to determine whether risk factors precede the development of CKD. Because CKD progression is inherently time-dependent, appropriate analytic approaches are required. Survival analyses and longitudinal risk modeling better capture trajectories of kidney function decline than cross-sectional assessments and provide more robust evidence; however, such analyses have not been performed in this population. Furthermore, VACTERL association is characterized by phenotypic heterogeneity and multifactorial etiology [3-5], complicating assessment of kidney prognosis and development of standardized risk models. Collaborative registries are particularly valuable in rare and heterogeneous conditions such as VACTERL association, where single-center cohort studies are limited by small sample size and potential selection bias.

The high prevalence of CAKUT in this population is consistent with a central role of structural kidney abnormalities in shaping long-term outcomes [1,2,4]. Congenital kidney anomalies are associated with reduced nephron endowment, which establishes a baseline susceptibility to kidney dysfunction. A diminished nephron number predisposes affected individuals to adaptive hyperfiltration in the remaining nephrons, leading to intraglomerular hypertension, progressive sclerosis, and decline in kidney function [6,7]. From this perspective, complex kidney anomalies represent more than anatomical findings; they constitute a structural substrate for chronic vulnerability. Their identification as independent risk factors reinforces the importance of baseline nephron reserve as a determinant of long-term kidney health.

In this context, CKD progression in VACTERL association can be conceptualized as the interaction between congenital structural vulnerability and superimposed kidney injury. Individuals with VACTERL association are frequently exposed to multiple kidney stressors throughout childhood, including repeated gastrointestinal and urologic surgeries, dehydration, infections, and nephrotoxic medications. Although each episode appears clinically distinct, cumulative insults compound underlying structural vulnerability. Growing evidence in pediatric nephrology indicates that AKI is not merely a transient event but is associated with subsequent CKD progression [8-11]. Severe or recurrent AKI has been linked to persistent inflammation, endothelial dysfunction, and tubular epithelial cell arrest, culminating in interstitial fibrosis and nephron loss [12]. Within this conceptual framework, severe AKI represents a clinically meaningful event that can shift the trajectory toward progressive CKD rather than an isolated complication.

Although surgical intervention was not associated with CKD development in the study by Kim and Cho [1], kidney outcomes in VACTERL association should not be viewed in isolation from extrarenal manifestations. A case-control study reported higher complication rates during dialysis and poorer transplant outcomes in affected individuals [2]. While kidney replacement therapy is feasible, both dialysis and post-transplant management are frequently complicated by urologic and systemic comorbidities, resulting in dialysis-related complications, modality changes, and graft dysfunction or failure [2]. These observations reinforce the importance of coordinated multidisciplinary care involving pediatric nephrologists, urologists, gastrointestinal surgeons, cardiologists, and primary care providers to optimize long-term kidney outcomes.

Given these complexities, structured and risk-stratified kidney surveillance is warranted. A simplified conceptual framework for such an approach is illustrated in Fig. 1. No consensus recommendations exist specifically for VACTERL association; however, the identification of complex kidney anomalies and severe AKI as risk factors provides a rational basis for risk stratification. Patients with complex structural anomalies, prior stage 3 AKI, or recurrent kidney insults require closer follow-up. According to the 2024 Kidney Disease Improving Global Outcomes (KDIGO) CKD guidelines [13], surveillance should include periodic assessment of estimated glomerular filtration rate, screening for albuminuria or proteinuria, blood pressure monitoring, and careful review of nephrotoxic exposures. Given the limited strength of existing evidence, large-scale, multicenter longitudinal studies using appropriate analytic methods are needed to establish evidence-based, risk-stratified surveillance strategies. Through multidisciplinary collaboration and data-driven approaches, improved long-term kidney outcomes can become an achievable goal for this medically complex pediatric population.

Fig. 1.

Conceptual approach to risk-stratified kidney surveillance in VACTERL association. Patients are categorized into higher- and lower-risk groups based on overall clinical assessment. Suggested surveillance strategies are illustrated for each group. This framework is intended as a practical conceptual aid rather than a validated protocol. VACTERL, vertebral, anal, cardiac, tracheoesophageal fistula with or without atresia, renal, and limb; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; BP, blood pressure.

Funding Statement

None.

Data availability statement

Data sharing is not applicable as no new data were created or analyzed in this study.