Urothelial barrier alterations and urinary tract infection susceptibility after voiding cystourethrography: evidence from pediatric cohorts and experimental models.

Abstract

Voiding cystourethrography (VCUG) involves transurethral catheterization and retrograde instillation of iodinated contrast media (ICM), both of which may contribute to VCUG-associated urinary tract infection (VCAUTI). This study investigated clinical factors associated with VCAUTI and explored potential urothelial mechanisms. A retrospective pediatric cohort was analyzed to identify factors associated with VCAUTI. Murine VCUG and VCAUTI models were established using intravesical iohexol or uropathogenic Escherichia coli (UPEC) resuspended in iohexol. Complementary in vitro experiments were performed using UPEC and SV-HUC-1 cells to assess bacterial behavior, urothelial apoptosis, and barrier-related protein expression. VCAUTI occurred in 12.3% of children. Children younger than 1 year and those with vesicoureteral reflux (VUR) had a higher risk of VCAUTI. In experimental models, iohexol exposure was associated with urothelial apoptosis, loss of tight junction proteins, and impaired barrier integrity, which may facilitate UPEC colonization. Saline bladder irrigation was associated with lower VCAUTI incidence in children with VUR. Contrast exposure within the procedural context of VCUG may be linked to urothelial barrier alterations and increased susceptibility to infection. Saline bladder irrigation may represent a potential preventive strategy, although prospective studies are needed to confirm its efficacy and safety. Key Message VCUG-related procedural factors, including contrast instillation, were linked with urothelial barrier alterations that may facilitate UPEC colonization and VCAUTI susceptibility. Saline bladder irrigation was associated with lower VCAUTI incidence in children with VUR. Novelty This study combines pediatric cohort, murine, and cellular data to explore potential mechanisms of VCAUTI and identifies age <1 year and VUR as important associated factors. These findings provide mechanistic insight into VCAUTI susceptibility and suggest that saline bladder irrigation may represent a simple preventive strategy. Prospective studies are needed to validate its efficacy and safety.