Abstract
IMPORTANCE: Although prior studies have suggested that the risk of renal scarring gradually increases with each febrile urinary tract infection (UTI), recent and detailed data are lacking. OBJECTIVE: To evaluate how the risk of renal scarring is associated with the number of febrile UTIs. DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis was performed from June 2018 to April 2019 of data collected in the context of 2 multicenter prospective studies (RIVUR [Randomized Intervention for Children With Vesicoureteral Reflux], conducted from June 2007 to June 2013, and CUTIE [Careful Urinary Tract Infection Evaluation], conducted from May 2008 to October 2013), of children with a first UTI without baseline renal abnormalities who were followed up for 2 years for febrile recurrences. EXPOSURE: Number of known febrile UTIs. MAIN OUTCOMES AND MEASURES: Renal scarring was defined as decreased uptake of tracer associated with the loss of contours or cortical thinning on a technetium 99m dimercaptosuccinic acid renal scan obtained at study exit or approximately 4 months after the last febrile UTI. RESULTS: A total of 345 children were included (307 girls and 38 boys; mean [SD] age, 19.4 [18.2] months; 221 with vesicoureteral reflux and 124 without vesicoureteral reflux). The incidence of renal scarring was 2.8% (95% CI, 1.2%-5.8%) after 1 febrile UTI, 25.7% (95% CI, 12.5%-43.3%) after 2 febrile UTIs, and 28.6% (95% CI, 8.4%-58.1%) after 3 or more febrile UTIs. The odds of renal scarring after a second febrile infection were 11.8 (95% CI, 4.1-34.4) times greater than after a single febrile infection, and the odds of renal scarring after 3 or more febrile infections were 13.7 (95% CI, 3.4-54.4) times greater than after a single febrile infection. CONCLUSIONS AND RELEVANCE: Although relatively few children have 2 febrile UTIs, those who do have a substantially higher risk of renal scarring compared with children with a single febrile UTI. This finding suggests that research should focus on the identification of biomarkers that could noninvasively identify children at risk for subsequent febrile infections. More research is also needed to understand the molecular basis of the increased risk of renal scarring among children with recurrent febrile UTIs.