eMedicine Specialties > Radiology > Pediatrics

Vesicoureteral Reflux

Author: Kevin F McCarthy, MD, Staff Physician, Department of Radiology, National Naval Medical Center
Coauthor(s): Veronica Rooks, MD, Military Chief of Pediatric Radiology, Pediatric Radiologist, Tripler Army Medical Center; Assistant Professor of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences
Contributor Information and Disclosures

Updated: Nov 12, 2009

Introduction

Background

Vesicoureteral reflux (VUR) is the abnormal flow of urine from the bladder into the upper urinary tract and the most common urologic disease in childhood. Its presence is pathologic, and it represents the most significant risk factor for childhood renal scarring and its sequelae.^{1,2,3,4,5,6,7,8,9,10}

The majority of cases (90%) in children represent a primary congenital failure of the natural passive 1-way mechanism of the ureterovesical junction (UVJ) to maintain unidirectional urine flow. A minority of VUR cases (10%) occur secondary to abnormalities of the ureteral insertion in association with renal transplantation, ureterocele (see Images 2-5), ureteral duplication anomalies (see Image 1), obstruction of the bladder outlet (posterior urethral valves in boys, see Image 6), dysfunctional voiding, or constipation.

Leonardo da Vinci was the first to describe and depict the UVJ. VUR was demonstrated experimentally in 1883, and the initial observation of VUR in humans was recorded in 1893. Reflux occurs naturally in some other species, including dogs, cats, and rabbits.

There is a documented association of VUR with congenital upper urinary tract abnormalities such as renal agenesis, multicystic dysplastic kidney, and obstruction of the ureteropelvic junction (UPJ).

Recent studies

According to Fefferman et al, fluoroscopically captured images are adequate in documenting the absence of vesicoureteral reflux (VUR) on VCUG examinations, making radiographic spot images unnecessary and thereby reducing patient exposure to radiation. The authors retrospectively reviewed 65 VCUG exams, each consisting of fluoroscopically captured spot (FCS) images and corresponding digital radiographic spot (DRS) images. The diagnostic accuracy of the FCS images regarding binary characterization of reflux as negative or positive was 97.2%; the sensitivity of the FCS images was 92.6%; and the specificity of the FCS images was 98.6%.¹

In a retrospective cohort study by Novak et al using data from the North American Pediatric Renal Trials and Collaborative Studies Registry, children with VUR were found to have a slower rate of progression to end-stage renal disease than children with renal aplasia, hypoplasia or dysplasia, and other causes of chronic kidney disease. In children with VUR as the cause of chronic kidney disease, the factors of older age, higher stage of chronic kidney disease, and history of urinary tract infection were significantly associated with the risk of progression to end-stage renal disease.²

Menezes and Puri, in a study of 251 siblings of 215 index patients with grade III to 5 VUR, noted that the familial nature of VUR is well recognized but that the screening of siblings for VUR remains controversial. In their study, the authors found that the incidence of sibling VUR is maximal in patients younger than 3 years and that reflux in these patients is usually high grade and associated with a higher incidence of renal scarring. Of the 251 siblings with reflux, 105 were diagnosed after a urinary tract infection and 146 after screening. A total of 207 siblings were younger than 3 years, and 44 were 3-6 years of age. Renal scarring was present in 35.5% of symptomatic siblings and in 15% of screened siblings. The authors recommended that screening be performed on all siblings who are younger than 3 years of index patients with grades III to V VUR.³

Pathophysiology

Renal scarring

Incomplete bladder emptying is a contributory factor, and post-voiding residual urine acts as a fertile incubation medium for urinary pathogens, predisposing children with vesicoureteral reflux (VUR) to pyelonephritis and resultant renal scarring.⁴ Radiologic evidence of renal scarring is present in 30-60% of children with VUR, and VUR is present in almost all children (97%) with severe renal scarring. However, most kidneys (60%) with acute cortical defects do not demonstrate reflux, which highlights that ascending urinary tract infection (UTI) is quite common despite the absence of demonstrated VUR.

The kidney is most susceptible to scarring from intrarenal reflux in the first year of life and probably at the time of first upper tract infection.⁵ Renal scars less frequently develop after age 5 years. New renal scars develop almost exclusively in the presence of UTI and intrarenal reflux, but the presence of intrarenal reflux alone does not equate with renal scarring. Infected urine is believed to cause an exudative reaction that leads to fibrosis and scarring of papillae. Intrarenal reflux is a phenomenon that is likely underreported due to its fleeting nature and occurrence at peak reflux.

Lower grades of reflux without bacteriuria probably cause no significant renal damage, although the subject has been debated.

Severity of reflux

The severity of VUR is directly related to the risk of pyelonephritis and subsequent renal scarring. VUR and renal scarring may lead to severe hypertension (in 10-20% of cases, mostly female), progressive renal insufficiency, and renal failure.

VUR is or has been present in 30-49% of children who have renal failure before age 16 years and in 20% of adults who have renal failure before age 50 years.

Reflux nephropathy is thought to be responsible for 10-30% of all cases of end-stage renal disease. Renal growth is impaired in patients with ongoing reflux and UTI. Spontaneous resolution of reflux or resolution after therapy allows for resumption of renal growth, but the affected kidney never catches up.

Frequency

United States

Vesicoureteral reflux (VUR) occurs more commonly in children who have had urinary tract infection (UTI) than in those with sterile urine, affecting about 0.4-1.8% of children without UTI, 14-35% of children with asymptomatic UTI, and 25-50% of children with symptomatic UTI undergoing voiding cystourethrography (VCUG).

In pediatric patients with UTI, an average of 35% (18-50%) are diagnosed with reflux. Some researchers hold that the prevalence of this condition in randomly selected children may be as high as 17%.

VUR is inherited in an autosomal dominant pattern with variable expression. The child of a parent with VUR has a 66% likelihood of having reflux and the sibling of a child with reflux has a 25-50% likelihood of being similarly afflicted. The risk of sibling reflux increases even further when evidence of renal damage is present in the index case.

About 75% of the siblings of patients are asymptomatic, and 20% of siblings of patients with dysfunctional voiding have reflux.

Mortality/Morbidity

The natural history of vesicoureteral reflux (VUR) is that it resolves spontaneously in childhood at a rate of about 10-15% per year.

• VUR resolves spontaneously before adolescence in approximately 90% of those with grade I reflux, in 80% of those with grade II reflux, in 50% of those with grade III reflux, in 10% of those with grade IV reflux, and essentially 0% in those with grade V reflux.
• For grades I-III, the overall rate is approximately 80%.
• Secondary reflux is not likely to improve spontaneously.

Race

Reflux is 10-20 times less frequent in black girls than in other girls.

Sex

Overall, about 75% of patients with vesicoureteral reflux (VUR) are girls.

• Urinary tract infection (UTI) is more frequent in girls than boys and occurs in school-aged children, with a female-to-male ratio of 20:1.
• The frequency of renal scarring among girls with VUR is about 8 times that of girls without reflux.
• In the prenatal period, VUR is suspected more frequently in boys than in girls, with a male-to-female ratio of 5:1. This ratio changes dramatically after birth, though there is disagreement regarding the incidence according to sex. Some authors note that follow-up studies of antenatally diagnosed reflux suggest a female-to-male ratio of 1.4:1 to 4.0:1, whereas others note a female-to-male ratio of 1:2.

Age

The average patient age at diagnosis is 2-3 years.

• With the advent of prenatal sonographic screening, the evaluation for hydronephrosis and possible contribution of vesicoureteral reflux (VUR) is being performed in the neonatal and infant period.
• Most cases of VUR resolve by about age 8 years, depending on the grade.

Anatomy

The pressure of bladder urine against the intravesical submucosal tunnel of the distal ureter effectively keeps it closed, except when ureteral peristalsis actively propels urine through it. The tunneled segment acts as a mainly passive 1-way valve. (There is a small contribution from the ureterotrigonal longitudinal muscles and ureteral peristalsis.)⁶

In primary vesicoureteral reflux (VUR), abnormal anatomic features are present: laterality of position, superior ectopia of a patulous ureteral orifice, a perpendicular (rather than oblique) course of the ureter through the bladder wall and a shortened intramural segment of ureter. The ratio of the submucosal tunnel length to the ureteral diameter is the primary factor determining the effectiveness of the normal valve mechanism. In healthy individuals, the ratio is typically 5:1, whereas it is about 1.4:1 in those with VUR. The intramural ureter increases in length from 0.5 cm at birth to 1.3 cm (adult length) by about age 12 years. The severity of reflux is proportional to the degree of anatomic abnormality.

Reflux is usually greatest and may be demonstrated only during the initiation or cessation of voiding, corresponding to the elevation in bladder pressure.

Intrarenal reflux favors the polar regions of the kidneys where there is a relative abundance of compound papillae that have larger, more perpendicularly oriented and concave duct orifices opening to the calyces. The obliquely oriented, slitlike convex duct orifices of the simple papillae found mostly in the mid kidney close readily with increased intrapelvic pressure, thereby preventing intrarenal reflux. Overall, at least two thirds of papillae in human kidneys are concave and have the potential to permit intrarenal reflux of urine.

Presentation

The relationship between vesicoureteral reflux (VUR) and infection is close and complicated. Despite a few lingering disagreements, it is now commonly agreed that VUR of infected urine is the major cause of pyelonephritis in children. A child with reflux is more likely to have pyelonephritis than a child without reflux, yet there is no significant difference in the incidence of sterile (88-90%) and infected (10-12%) urine in children who do not have reflux compared with those who do. The issue of whether infection can produce significant VUR without some underlying abnormality has been a point of contention. Some reflux may occur secondary to urinary tract infection (UTI), but this generally resolves spontaneously with treatment of the infection and disappearance of the inflammatory changes at the UVJ.

The symptomatic presentation of VUR is almost always in conjunction with an associated UTI. Fever is considered the most important symptom in differentiating upper tract infection (pyelonephritis) from lower tract infection (cystitis). Distinguishing between the two on clinical grounds is difficult in young children.

An important risk factor for recurrent UTI and VUR is voiding and elimination dysfunction. This may be due to a small bladder volume, uninhibited bladder contractions, or bladder overdistention from willful infrequent voiding. Primary VUR takes 1.5 years longer to resolve in children with dysfunctional urinary and fecal elimination, and there are more breakthrough infections and reimplantation surgeries than in those without this condition. The diagnosis of dysfunctional elimination in patients with VUR is important because effective nonoperative treatments exist that have been shown to reduce the number of UTIs and promote the resolution of VUR. Some contrary data has recently been published where no association between the diagnosis of UTI or VUR and dysfunctional elimination in school-aged children of the general pediatric population.

VUR is the most common abnormality associated with complete ureteral duplication. Approximately 10% of children undergoing antireflux surgery have complete or incomplete duplication of the collecting system. In only 22% of patients with renal duplication does VUR spontaneously resolve. Imaging of completely duplicated ureters in patients with VUR most often follows the Weigert-Meyer rule: The upper pole, often obstructed, ectopic ureteral orifice inserts medial and caudal to the often refluxing lower pole ureteral orifice. Reflux occurs 3 times more often into the lower pole ureter.

VUR is associated with UPJ obstruction. The incidence of reflux in patients with UPJ obstruction has been reported as 5-24%. Deciding which of the two is the more significant lesion is sometimes a challenge in uroradiology.

Preferred Examination

Voiding cystourethrography (VCUG) is the screening urologic imaging study of choice. American urologists, pediatricians, and radiologists recommend this study to detect vesicoureteral reflux (VUR), ureterocele (see Image 4), posterior urethral valves in boys (see Image 6), or bladder wall thickening (see Image 29).

Up to 50% of children with proven urinary tract infection (UTI) undergoing VCUG have some degree of reflux. Sonography of the kidneys should be performed in conjunction with VCUG to document the size of the kidneys and to look for obstruction, hydronephrosis, or other congenital malformations.⁷

When VUR is found to distend the upper tract, postvoiding decompression at the upper tracts should be observed.

Limitations of Techniques

Reflux is generally intermittent and may escape detection on voiding cystourethrogram (VCUG). This difficulty may be compounded by the desire to limit the child's exposure to ionizing radiation as much as possible. The influence of body position on the occurrence and detection of reflux has not been well studied in children. Incomplete bladder filling decreases the sensitivity of the study.

Differential Diagnoses

Bladder, Cystitis
Multicystic Dysplastic Kidney
Posterior Urethral Valve
Reflux Nephropathy
Ureterocele

Other Problems to Be Considered

Megaureter
Neurogenic bladder
Bladder neck obstruction
Posterior urethral valve
Dysfunctional voiding

• Search for CME/CE on This Topic »

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• Vesicoureteral Reflux (Urology)
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• Pyelonephritis, Chronic (Nephrology)

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• Urinary Tract Infection: Finding an Answer When Conventional Testing Is Not Helpful
• Pediatric Voiding Dysfunction: Current Evaluation and Management