Why Does Prevention of Recurrent Urinary Tract Infection not Result in Less Renal Scarring? A Deeper Dive into the RIVUR Trial.

purposeThe RIVUR (Randomized Intervention for Children with Vesicoureteral Reflux) trial reported that antibiotic prophylaxis reduced recurrent urinary tract infection but antibiotic prophylaxis was not associated with decreased new renal scarring. However, the original reports did not assess the relationship among recurrent urinary tract infection, new renal scarring and antibiotic prophylaxis in detail. Therefore, we investigated the relationship among these issues. MATERIALS AND

methodsWe included subjects with dimercaptosuccinic acid scan within 6 months of enrollment and at least 1 followup dimercaptosuccinic acid scan from the RIVUR trial. The primary outcome was recurrent urinary tract infection associated new renal scarring, defined as recurrent urinary tract infection and new changes on dimercaptosuccinic acid scan. Due to a low number of events, propensity score was used to adjust for confounders. Multivariate logistic regression was fitted to investigate the associations between the covariates and the outcome.

resultsA total of 489 patients (91% female, mean age 20.3 months) were included in the study. Any new renal scarring was more common among those with recurrent urinary tract infection (OR 4.1, 95% CI 2.0-8.5, p <0.01) after adjusting for age, sex, index urinary tract infection, duplication, bowel bladder dysfunction and antibiotic prophylaxis. Recurrent urinary tract infection associated new renal scarring occurred in 5 of 244 (2%) patients on antibiotic prophylaxis and 13 of 245 (5%) on placebo. Compared to antibiotic prophylaxis, placebo was associated with a higher risk of recurrent urinary tract infection associated new renal scarring (OR 3.1, 95% CI 1.0-8.8, p=0.04) after adjusting for age, sex, race, index urinary tract infection, bowel bladder dysfunction, duplication, hydronephrosis, vesicoureteral reflux grade and baseline renal scarring. There were no differences in scar severity at final dimercaptosuccinic acid scan (p=0.88) or change from baseline (p=0.53) between antibiotic prophylaxis and placebo.

conclusionsRecurrent urinary tract infection was associated with new renal scarring in the RIVUR trial. When limited to recurrent urinary tract infection associated new renal scarring, antibiotic prophylaxis was associated with a decreased risk of this outcome. It remains unclear why new renal scarring developed in a proportion of subjects without recurrent urinary tract infection. The results should be carefully interpreted due to the inherent limitations.