Therapeutic Management of Children with Vesicoureteral Reflux

“...VUR represents a risk factor for UTI development, distinguishing two different entities related to it, “reflux disease” and “reflux symptom”; the first involves predominantly males, with a rare incidence, prenatally or under two years of age, with severe VUR (stage IV–V), abnormal renal parenchyma and urinary tract, and spontaneous resolution in 50% of cases. 

"The second and more common form of VUR is usually assessed in females, with low-grade I–III VUR, associated with normal kidneys and urinary tract, with a high rate of resolution (80–90%).

"A voiding cystourethrogram (VCUG) is the 'gold standard' for VUR detection, allowing grading of the severity from a wisp of contrast just beyond the bladder with no dilatation of the ureter or collecting system (grade I) up to dilatation and tortuosity of the ureters with calyceal clubbing (grade V). This radiologic test is an invasive procedure requiring urethral catheterization, often painful and traumatic for the child, causing UTIs in 1 to 3% of cases."

"Although a diagnostic study can be achieved with a relatively low radiation dose by using careful technique and modern equipment, in practice, the range of doses is extremely wide.”

“Other tests have been proposed to detect reflux, such as contrast-enhanced voiding urosonography (ceVUS), an ionizing radiation-free technique using ultrasound with a contrast agent instilled into the bladder to image the urinary tract. Several studies revealed ceVUS as a valid alternative method for VUR assessment, with comparable results in terms of sensitivity and specificity with a VCUG in detecting and grading VUR.”

“Behind radiological procedures, several urinary biomarkers are being studied to achieve early diagnosis, facilitating staging and therapeutic VUR management. In particular, some interleukins or neutrophil gelatinase-associated lipocalin have been associated with the innate immune reaction and proinflammatory state characterizing children with VUR, with potential clinical application to easily identify patients who require antibiotic prophylaxis or surgical intervention.”

“However, prospective and larger studies are needed to confirm the role of these or other biomarkers as alternative, non-invasive tools to VCUG and ceVUS.”

“The choices of the patients and the radiological test to perform are not unique challenges, considering that the therapeutic approach of VUR is a matter of debate.”

"There are two distinct directions in the literature regarding the investigation of an uncomplicated first febrile UTI in a child. In general, when presented with a first febrile UTI in a child, physicians recommend fewer investigations and less treatment, in contrast to surgeons who advocate extensive investigation and aggressive intervention if imaging detects an abnormality [19]."

"Moreover, the child affected by VUR undergoes renal scintigraphy to complete the diagnostic process, evaluating the function of the kidneys. The risk of a child without other congenital abnormalities of the kidney and urinary tract developing chronic kidney disease as a result of repeated febrile UTIs associated with VUR is very low."

"Spontaneous resolution of VUR can be observed in about more than 80% of grades I and II, around 45% of grade III, and less than 10% of grades IV and V. According to the main international guidelines, VUR therapy is based on three strategies, depending on the severity of VUR and physicians’ preferences."

"In children without UTI symptoms and with low grades of VUR, the 'wait and watch' approach could be considered due to the high probability of spontaneous resolution."

"If it is known that VUR could resolve spontaneously over time, waiting for this to occur rather than treating it should only happen in the absence of repeated febrile UTIs, a risk factor for renal scarring."

"However, regular follow-up visits are required to enable adequate monitoring of the patient’s status, and this approach is recommended for patients with a relatively low risk of renal injury, such as males with low-grade VUR."

"Conversely, independently from the severity of the VUR, in children with LUTS and recurrent UTIs, continuous antibiotic prophylaxis (CAP) could be prescribed [26]."

"Whether VUR contributes to the risk of chronic kidney disease (CKD) remained unclear."