Ureteral diameter ratio predicts breakthrough febrile UTI in children with primary vesicoureteral reflux

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INTRODUCTION: Children with primary vesicoureteral reflux (VUR) may be placed on continuous antibiotic prophylaxis (CAP) to reduce the risk of urinary tract infections (UTI). Despite the use of CAP, up to 36 % of children with VUR still develop febrile breakthrough UTI (BT-UTI). It has been suggested that ureteral diameter ratio (UDR) may predict febrile BT-UTI in children with primary VUR. We sought to validate this finding in a large cohort of children with primary VUR on CAP. METHODS: We reviewed a prospectively maintained database of children with primary VUR at a single children's hospital from October 2015 to May 2023. Children were treated at clinician discretion. We included children with primary VUR on CAP with available voiding cystourethrogram (VCUG) imaging. UDR was calculated on VCUG by measuring the largest distal ureteral diameter within the false pelvis and dividing by the distance between the bottom of the L1 vertebral body and the top of the L3 vertebral body, as previously described. In children with bilateral VUR, the higher-grade reflux and the larger UDR were used. Children with ureteroceles, duplicated systems, and secondary VUR were excluded. The primary endpoint was febrile BT-UTI. Univariate and multivariate statistical analyses were conducted. RESULTS: Of the 257 children in the VUR database, 132 met inclusion criteria. The median age at VCUG was 1.1 years (IQR 0.2-4.9). Females constituted 54.5 % of the cohort. VUR grades included grade 1 (9.8 %), grade 2 (15.9 %), grade 3 (31.8 %), grade 4 (25.0 %), and grade 5 (17.4 %). The average UDR was 0.312 (range: 0-0.951). For each 0.1 increase in UDR, there was a significant increase in the risk of breakthrough fUTI (OR = 1.43, 95 % CI 1.06-1.91; p = 0.016). With a median follow-up time of 2.4 years (IQR 1.2-4.6), 21 (15.9 %) children developed a breakthrough fUTI while on CAP. The area under the receiver operating characteristic curve (AUC) was 0.72 (p = 0.0006). UDR risk-stratification of febrile BT-UTI included low-risk UDR (<0.250; BT-UTI: 12.1 %), intermediate-risk UDR (0.250-0.500; BT-UTI: 17.1 %), and high-risk UDR (>0.500; BT-UTI: 24.0 %). CONCLUSION: UDR is an independent risk factor to predict febrile BT-UTI in children with primary VUR on CAP. To our knowledge, this is the first and largest study to validate this finding. We propose a UDR risk stratification that may be useful in individualizing care among children with primary VUR.

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