Bladder volume at onset of vesicoureteral reflux is an independent risk factor for breakthrough febrile urinary tract infection, "Beyond the Abstract," by Christopher S. Cooper, MD, FACS, FAAP

BERKELEY, CA ( - VUR treatment goals include prevention of febrile infections, prevention of renal injury, and minimizing morbidity of treatment and follow-up. An individualized approach to accomplishing these goals should be taken, considering a variety of individual risk factors. Antibiotic prophylaxis in children with VUR or recurrent UTI has been widely employed and the reduction in UTIs in those children receiving prophylaxis with VUR has been reaffirmed by two recently published large, multi-institutional studies.[1, 2] Despite prophylactic antibiotics, over a quarter of the patients in our study experienced a febrile breakthrough infection. Similar to other reports, both dilating reflux and a history of prior fUTI were independently predictive of breakthrough infections. Higher grades of reflux likely translate into a risk of a larger inoculum of bacteria placed in the kidneys from a child with bacteria in the bladder. In addition to a greater number of bacteria placed in the kidney, it seems likely that either repeated inoculation or longer duration of exposure would also increase the risk of developing pyelonephritis. In this study we demonstrated that VUR occurring at low bladder volumes was associated with an increased likelihood of fUTI over time, independent of other variables including grade of VUR. The onset of reflux during a cystogram has previously been shown to affect the likelihood of spontaneous resolution, with later onset of reflux normalized for age predicted bladder capacity (PBC) demonstrating higher resolution rates.[3, 4]

In this study, children with reflux at ≤ 35% PBC were over 1.5 times more likely to experience a breakthrough fUTI than those with VUR occurring at higher bladder volumes. We speculate that this is because children with VUR occurring earlier during bladder filling have increased duration of exposure of the kidneys to the occasional bacteria from within the bladder compared to those children with reflux that occurs late in filling or only during voiding. This increased exposure to bacteria may amplify their risk of developing pyelonephritis. Conversely, children with reflux occurring later in bladder filling or voiding are at decreased risk of recurrent pyelonephritis. The impact of bladder volume at the onset of VUR constitutes an additional clinical variable that should be considered along with multiple other clinical variables in determining clinical management to maximize benefit and minimize risk. Children with vesicoureteral reflux occurring at low bladder volumes are at increased risk for breakthrough febrile urinary tract infections independent of reflux grade. This easily reportable variable on VCUG has previously been demonstrated as an independent predictive factor for spontaneous resolution of VUR.

Our findings emphasize the importance of routinely noting the bladder volume at the onset of VUR during VCUG to provide additional prognostic information about risk of pyelonephritis and assist with clinical decision making and counseling.


  1. Brandstrom P, Esbjorner E, Herthelius M, et al. The Swedish Reflux Trial in Children: III. Urinary tract infection pattern. J Urol 2010;184:292
  2. The RIVUR Trial Investigators. Hoberman A, Greenfield SP, Mattoo TK, et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med 2014;370:2367
  3. McMillian ZM, Austin JC, Knudson MJ, et al. Bladder volume at onset of reflux on initial cystogram predicts spontaneous resolution. J Urol 2006;176:1838;
  4. Knudson MJ, Austin JC, Wald M, et al. Computational model for predicting the chance of resolution in children with vesicoureteral reflux. J Urol 2007;178:1824


Written by:
Christopher S. Cooper, MD, FACS, FAAP as part of Beyond the Abstract on This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Professor and Vice Chairman of Urology
Director of Pediatric Urology
University of Iowa Hospitals and Clinics
Iowa City, IA USA

Bladder volume at onset of vesicoureteral reflux is an independent risk factor for breakthrough febrile urinary tract infection - Abstract

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