A Risk Stratified Approach for Conservative Management of Vesicoureteral Reflux in a Prospective Cohort
Sarah A. Holzman, MD, Kathy H. Huen, MD, Carol A. Davis-Dao, PhD, Omar Abuzeid, BS, Elias J. Wehbi, MD, Heidi A. Stephany, MD, Kai-Wen Chuang, MD, Antoine E. Khoury, MD.
CHOC Children's and UC Irvine, Orange, CA, USA.
Background: In a re-analysis of the RIVUR trial raw data, our group previously demonstrated that continuous antibiotic prophylaxis (CAP) was significantly beneficial in one third of the study population who were stratified as high risk. However, we were unable to detect a benefit from CAP in the patients stratified as low risk. Starting in 2014, we prospectively followed a cohort of vesicoureteral reflux (VUR) patients using a risk stratified approach. We hypothesized that low risk patients with VUR could be maintained off CAP without resulting in a higher urinary tract infection (UTI) rate.
Methods: Patients with primary VUR diagnosed by voiding cystourethrogram aged 1 day to 6 years were enrolled prospectively from 2014-2021. Children with secondary VUR, ureterocele, duplication anomalies, multicystic dysplastic kidney, ectopic ureter on same side of reflux, or less than 1 month of follow-up were excluded. Patients were stratified into low or high-risk groups based on their clinical risk factors (Figure). CAP was recommended only to patients in the high-risk group. Primary outcome was UTI development. Multivariable Cox regression analysis was used to estimate adjusted UTI risk.
Results: Of 406 patients, 271 met inclusion criteria. Median age at initial visit was 7 months (IQR 3.1-15). Forty eight percent (130/271) were male and 77% (100/130) were uncircumcised. Twenty one percent (56/271) were stratified to low risk and the remaining 215 patients were stratified as high risk. Sixty six percent (178/271) had grades I-III VUR and 21% (58/271) developed UTI during follow-up.Independent UTI predictors on multivariable analysis were: female sex (HR 5.0, 95% CI: 1.2-21, p=0.03), grades IV-V VUR (HR 2.3, 95% CI: 1.3-4.1, p=0.005), and age under 6 months at initial visit (HR 3.4, 95% CI 1.7-6.6, p=0.0004). When adjusting for CAP with intention to treat analysis, female sex, grades IV-V VUR, and age under 6 months at initial visit remained significant as independent UTI risk factors. In the subgroup of patients stratified to the low-risk category (n=56), UTI rate was 12.5% (7/56), which was comparable to RIVUR re-analysis UTI rate for low-risk patients (16.5%, 64/389). Twenty-four percent (51/215) of patients stratified to high risk developed UTI. The majority of low-risk patients in our study did not receive CAP and their UTI rate was 11% (4/35), similar to the UTI rate of low-risk patients on placebo in the RIVUR re-analysis (19%, 37/193). The remaining 21 patients in the low-risk stratification group received antibiotic prophylaxis per provider or family preference and their UTI rate was 14% (3/21).
Conclusions: In our study, patients stratified as low risk had similar UTI rates to the low-risk children in the RIVUR trial. These results confirm that outside of a randomized controlled trial, low risk
VUR patients can be safely maintained off of CAP without an increased UTI risk. Our future risk stratification models should take young age at presentation into account as a UTI risk factor. 
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