The Second Time Around: Ultrasound, Overdiagnosis, and the Value of Waiting

Infants and young children with their first febrile urinary tract infection (fUTI) often require hospitalization. While the American Academy of Pediatrics (AAP) clinical practice guideline on the diagnosis and management of initial fUTI has been retired,1 the recommendation to perform renal bladder ultrasonography (RBUS) is often followed, given its noninvasive nature and ability to demonstrate acute obstruction and abscess as well as structural abnormalities. The guideline recommended this imaging within 2 days for patients with severe or non-improving infections. A delay in imaging may be superior for those with substantial clinical improvement to avoid finding dilatation and uroepithelial thickening (UET) related to the infection that may be confused with a structural abnormality. These findings may prompt interventions such as urologic referral or voiding cystourethrogram (VCUG), exposing the patient to unnecessary costs, pain, and radiation. Delayed imaging has the possibility of loss to follow-up, with potential deleterious consequences for patients with undiagnosed severe structural abnormalities. Published in this issue of the journal, Marsh et al conducted a multicenter retrospective cohort study of 294 patients across 6 geographically and structurally diverse children’s hospitals between 2018 and 2022 to assess whether early RBUS—defined as less than 24 hours from last fever—was associated with higher rates of transient abnormalities and whether delaying imaging risked loss to follow-up in children aged 2 to 24 months hospitalized for a fUTI.2The authors sought to answer 3 practical questions: (1) Does early RBUS yield more false positives, particularly urinary tract dilatation or UET? (2) What is the downstream impact of abnormal RBUS findings on further imaging and referrals? (3) What proportion of children are lost to follow-up when RBUS is deferred to the outpatient setting?Their findings are both illuminating and cautionary. Of the 282 children who received RBUS, 63% were imaged early. Abnormal findings were significantly more common in the early group than in the late group (64.4% vs 40.7%, P < .001), with UET disproportionately represented among early ultrasonography. However, this result was confounded by site-level variability: Only 1 hospital documented UET, and it also had the highest proportion of early RBUS. When this site was excluded in post hoc sensitivity analysis, the difference in abnormal RBUS finding rates between early and late groups lost statistical significance (55.0% vs 39.7%, P = .069). A second sensitivity analysis excluding only patients who had UET showed no difference in urinary tract dilatation between early and late imaging (11.9% vs 12.3%, P = .912).Despite the ambiguity around imaging findings, the study demonstrates that early RBUS is associated with more downstream testing. Children imaged early were significantly more likely to undergo VCUG (29.9% vs 16.0%, P = .018) and receive urology referrals (17.5% vs 7.4%, P = .032). Interestingly, when using VCUG results to assess RBUS findings, the false-positive rate of RBUS was similar between early and late groups (54.7% vs 46.2%, P = .579).Rather than pursuing a VCUG for patients with abnormal RBUS findings, some clinicians opted for a repeat RBUS, a strategy that may merit broader consideration. Among the 50 children who received a second ultrasonography, nearly half (46%) had normal follow-up imaging results. Resolution rates were notable across specific findings: Hydronephrosis resolved in 3 of 9 cases (including 1 classified as severe), hydroureter in 5 of 6, UET in 7 of 12, and mild pelviectasis in 9 of 17. These data support the hypothesis that many abnormalities seen on early RBUS reflect transient inflammatory changes rather than structural pathology.The study also underscores the risk of deferring imaging to the outpatient setting. Of the 27 children who did not receive inpatient RBUS, 12 (44.4%) were lost to follow-up. This is a sobering statistic, especially given that missed imaging occurred across 5 of the 6 sites. While delaying RBUS may reduce false positives, it must be balanced against the real-world risk of missed diagnoses due to incomplete follow-up.Length of stay did not differ between early- and late-imaging groups, suggesting that delaying RBUS until the child is afebrile for at least 24 hours does not compromise discharge timing. A strategy of performing RBUS closer to discharge may optimize diagnostic accuracy without prolonging hospitalization.The diagnosis of low-grade vesicoureteral reflux (VUR) often represents overdiagnosis—the identification of a condition that would never have caused symptoms or harm if left undiscovered. In medicine, overdiagnosis refers to detecting abnormalities that meet the technical definition of disease but are clinically insignificant, leading to unnecessary anxiety, monitoring, or treatment. The AAP guideline authors reanalyzed individual patient data from 6 randomized controlled trials and did not find a benefit of antibiotic prophylaxis in preventing recurrence of fUTI in patients with grade I to IV VUR, supporting the supposition that low-grade VUR represents overdiagnosis. Among the 1091 patients in this analysis, only 5 had grade V VUR, and they were excluded due to low numbers. Additionally, the guideline authors noted that the incidence of renal scarring is low until the third infection.3In the current cohort, only 2 children were found to have grade V VUR. One had persistent UET; the other had severe hydroureter and hydronephrosis that improved slightly on repeat imaging. Given the rarity of high-grade VUR, the lack of an identified benefit of diagnosing low-grade VUR, and the fact that scarring stays relatively stable until after the second or third febrile UTI, the best screen for VUR is the second fUTI.Other strategies to increase the yield of the VCUG include focusing on risk factors for high-grade VUR, such as non–Escherichia coli pathogens and bacteremia.4,5 Infants and children with these risk factors should be closely followed until appropriate imaging or referral has been obtained. Indeed, both patients with grade V VUR in the current study had non–E coli pathogens.All of these management strategies rest on the assumption that preventing pyelonephritis will in turn prevent reflux nephropathy, thereby reducing the risk of hypertension and end-stage renal disease. These are important outcomes, but because they often take years to manifest, most studies rely on the surrogate end point of renal scarring. Notably, the pattern of scarring differs between male and female patients—male patients tend to have more diffuse, global scarring and are more likely to develop hypertension and renal failure over time, whereas female patients more often have focal scars associated with recurrent UTIs and a better prognosis.6 This distinction lends support to the hypothesis that a subset of reflux nephropathy, particularly the male pattern, represents congenital renal dysplasia rather than acquired injury. In these children, the kidneys may be developmentally abnormal from birth and destined to become hypertensive or fail over time, regardless of early detection and management of VUR. Even if renal damage associated with high-grade VUR is not fully preventable, recognizing it remains important—as a marker of underlying renal vulnerability and as an opportunity to optimize care when symptoms arise. Ultimately, however, the best way to identify these patients, while minimizing unnecessary interventions for most patients without high-grade VUR, is to (1) concentrate on risk factors like non–E coli pathogens and bacteremia, (2) delay inpatient RBUS until close to discharge, (3) repeat early abnormal RBUS findings before proceeding to VCUG, or (4) consider skipping the VCUG on the first infection and wait for the second time around.