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Siobhan E. Alexander, BS1, Douglas W. Storn, MD, FACS, FAAP2, Kathleen Kieran, MD, FACS, FAAP2, Christopher S. Cooper, MD, FACS, FAAP2.
1University of Iowa College of Medicine, Iowa City, IA, USA, 2University of Iowa, Iowa City, IA, USA.

BACKGROUND: There is increased recognition of the need to selectively identify those children with VUR at increased risk for pyelonephritis. Previous studies demonstrate higher grades of reflux increase the risk for pyelonephritis and renal scarring. Prior work has also demonstrated that VUR with onset early during bladder filling on cystogram is less likely to resolve independent of grade compared to VUR occurring later during filling or voiding. We hypothesized that reflux occurring earlier in filling would increase the risk for pyelonephritis independent of grade since upper tracts may be exposed to longer periods of bacteria from the lower tract.
METHODS: We retrospectively reviewed 255 children with VUR in whom the bladder volume at VUR onset was known (208 girls; 47 boys; mean age 3.1 years ± 2.6). The bladder volume at onset of VUR was normalized for age predicted bladder capacity (PBC) and these values were updated with each patient’s subsequent cystogram. Variables assessed and controlled for included age, gender, reflux grade, laterality, bowel-bladder dysfunction, and prior UTI history (febrile vs. non-febrile; number of UTIs). Outcome was defined as having a febrile UTI that broke through prophylactic antibiotics.
RESULTS: As anticipated, a history of febrile UTIs, dilating grades of VUR, and bowel-bladder dysfunction were associated with a significantly increased risk for breakthrough UTIs in this population (HR = 2.17; CI 1.33,3.85; p=0.009); (HR=1.60; CI 1.05,2.42; p= 0.028), and (HR= 0.99,2.75; p=0.051), respectively. Median bladder volume at onset of VUR in those with breakthrough UTIs was significantly lower compared to those who did not develop a UTI (33% vs. 47%; p=0.006). The independent impact of bladder volume at onset of VUR on risk of breakthrough UTIs was performed controlling for other variables including VUR grade. Patients with onset of VUR at <35% PBC had a significantly increased risk of breakthrough UTI compared to reflux occurring at ≥35% PBC, HR =1.58; 95% CI (1.05, 2.38; p=0.029).
CONCLUSIONS: Children with early onset of VUR during bladder filling are at increased risk for developing breakthrough UTI independent of other risk factors, including high grade VUR. Our findings suggest that to better individualize patient management, bladder volume at onset of VUR should be routinely recorded during cystograms and considered by the pediatric urologist along with other well known factors to help stratify children regarding their risk of pyelonephritis and chance for spontaneous VUR resolution.

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