eMedicine Specialties > Radiology > Pediatrics

Vesicoureteral Reflux

Kevin F McCarthy, MD, Staff Physician, Department of Radiology, National Naval Medical Center
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

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.

Transverse gray-scale sonogram demonstrates a small left ureterocele in a patient with a low-grade vesicoureteral reflux. Ultrasonography may be the most helpful means to evaluate a patient for a ureterocele, as this is often difficult to visualize on early filling of the bladder during voiding cystourethrography. Patients with gross anatomic abnormalities of the urinary tract are not likely to improve without corrective surgery. In this case, the ureterocele measured less than 1 cm in all dimensions and appeared intermittently throughout the examination.

Sonogram of a large, obstructing ureterocele in a patient with vesicoureteral reflux. The thin rim of the ureterocele is best noted on the inferior most aspect of the bladder. This ureterocele measured 4 cm in greatest dimension and is outlined by contrast material in Image 4. Note the dilated, left-sided refluxing ureter.

Voiding cystourethrogram (VCUG) demonstrates a large, smooth, central filling defect peripherally outlined by contrast material. The catheter is deviated to the patient's right. This finding is consistent with a large ureterocele.

Excretory urogram demonstrates the classic cobra-head appearance of a ureterocele.

Voiding cystourethrogram (VCUG) demonstrates a posterior urethral valve.

Voiding cystourethrogram (VCUG) shows grade I left VUR. Incidentally noted is vaginal reflux.

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).

Excretory urogram demonstrates the classic cobra-head appearance of a ureterocele.

Voiding cystourethrogram (VCUG) shows grade I left VUR. Incidentally noted is vaginal reflux.

Voiding cystourethrogram (VCUG) show a large, distended bladder with irregular and trabeculated margins. This patient had posterior urethral valves.

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

Radiography

Voiding cystourethrogram (VCUG) demonstrates grade II VUR into the upper-pole moiety of a duplex collecting system and grade III VUR to the lower-pole moiety.

Grade II vesicoureteral reflux in a patient with ureteral duplication.

Voiding cystourethrogram (VCUG) demonstrates bilateral grade III reflux. The renal pelvis is mildly dilated on the right. There is some mild blunting of the calyceal fornices and loss of papillary impressions in the upper poles bilaterally.

Voiding cystourethrogram (VCUG) of lower ureter and ureterovesical junction in a patient with grade III reflux. The ureteral insertion on the left is between the 3- and 6-o'clock positions. There is a small bladder diverticulum at the ureteral insertion.

Voiding cystourethrogram (VCUG)demonstrates bilateral grade III vesicoureteral reflux.

Longitudinal sonogram corresponding to a voiding cystourethrogram (VCUG) of a grade III vesicoureteral reflux. Note the mild pelviectasis. The degree of pelviectasis or caliectasis does not correlate with the degree of reflux seen on the VCUG.

Voiding cystourethrogram (VCUG) demonstrates high-grade IV vesicoureteral reflux in a patient with a duplicated collecting system.

Grade III vesicoureteral reflux and periureteral-type diverticulum.

Voiding cystourethrogram (VCUG) of the left kidney demonstrates grade V vesicoureteral reflux.

Voiding cystourethrogram (VCUG) demonstrates a tortuous, dilated ureter in a patient with grade V vesicoureteral reflux.

Unilateral grade V vesicoureteral reflux secondary to a posterior urethral valve. There is gross dilatation of the renal pelvis and calyces. Papillary impressions are not visible. Gross intrarenal reflux is also identified.

Nuclear cystograms demonstrate grade III reflux. Reflux to the left kidney is shown, with dilatation of the renal pelvis.

Findings

The diagnosis of vesicoureteral reflux (VUR) is accurately established with fluoroscopic voiding cystourethrography (VCUG). This study permits assessment for the presence and extent of reflux, and it clearly delineates the bladder outline, bladder neck, and ureteral and urethral anatomy. Fluoroscopic VCUG also gives an accurate estimation of bladder capacity.

The retention of contrast material within the upper tracts after voiding without decompression suggests UPJ or ureterovesical junction (UVJ) obstruction. VUR may occur with bladder filling, during voiding, or both. Cyclical VCUG, repeated bladder filling and fluoroscopic examination, which is primarily performed in patients younger than 1 year, depicts reflux an additional 10% of the time.

In children older than 3-4 years who have signs only of lower UTI, VCUG is not recommended if renal sonograms are normal. Whether VCUG is done while the initial UTI is being treated or several weeks afterward is not important, so long as the child is responding appropriately to treatment and has normal bladder function. VCUG may be performed as soon as the urine is sterile and bladder irritability has disappeared.

VUR is graded according to the International Reflux Classification outlined by the International Reflux Study Group in 1985. This classification scheme is widely accepted and no new schemes have been introduced.

• Grade I - Reflux into the ureter only (see Image 7)
• Grade II - Reflux into the collecting system, without dilatation (see Images 8-9)
• Grade III - Reflux into the collecting system with mild dilatation, slight ureteral tortuosity, and no or slight blunting of the fornices (see Images 10-12)
• Grade IV - Moderate dilatation and/or tortuosity of the ureter and moderate dilatation of the renal pelvis and calyces, with complete obliteration of the sharp angle of the fornices but maintenance of the papillary impressions in the majority of calyces (see Images 14-15)
• Grade V - Gross dilatation and tortuosity of the ureter, with gross dilatation of the renal pelvis and calyces and nonmaintained papillary impressions (see Images 16-18)

Intrarenal reflux appears as contrast medium extending from the calyces into the polar renal collecting tubules in the form of striations. This can be identified most often in neonates and infants with moderate or severe reflux (5-15%). The presence of intrarenal reflux does not change the grade or treatment of VUR.

Nuclear imaging and sonography have replaced excretory urography (EU) as the preferred radiologic examination of the upper urinary tract. On excretory urograms, the scars of reflux nephropathy are typically detected about 2 years after infection. When uncomplicated, they have characteristic imaging features that include a deformed (clubbed) calyx and thinning of the overlying renal parenchyma, often with a notch in the surface of the kidney immediately opposite the affected calyx. Ureteral dilatation suggesting VUR may also be seen.

Degree of Confidence

EU is a modality rarely used in the modern assessment of VUR. It can demonstrate renal scarring but is less sensitive than DMSA or GH scintigraphy. The use of EU is exceptional and indicated only in those cases presenting with confusing collecting system anatomy or where demonstration of the calyces is important.

Computed Tomography

Nonenhanced CT scan in a 12-year-old boy demonstrates marked hydronephrosis and cortical thinning in a patient with grade V vesicoureteral reflux and a history of a posterior urethral valve. Note the free fluid in the pararenal space consistent with forniceal rupture after minor trauma to the abdomen (from football practice).

Sagittal sonogram of the bladder. A Foley catheter is surrounded by thickened, hypertrophied bladder wall, the sequelae of posterior urethral valves in this boy with bilateral grade V vesicoureteral reflux. Note the dilated right ureter.

Findings

Although CT can provide excellent anatomic and functional information in children with reflux nephropathy, it does not currently have a primary role in the usual diagnostic algorithm or follow-up of such children. Still, hydronephrosis and ureteral dilatation are easily seen in patients with vesicoureteral reflux (VUR) who happen to undergo CT examination (see Images 21-22).
 

Nonenhanced CT scan in a 12-year-old boy demonstrates marked hydronephrosis and cortical thinning in a patient with grade V vesicoureteral reflux and a history of a posterior urethral valve. Note the free fluid in the pararenal space consistent with forniceal rupture after minor trauma to the abdomen (from football practice).

Sagittal sonogram of the bladder. A Foley catheter is surrounded by thickened, hypertrophied bladder wall, the sequelae of posterior urethral valves in this boy with bilateral grade V vesicoureteral reflux. Note the dilated right ureter.

Magnetic Resonance Imaging

Findings

Although MRI can provide excellent anatomic and functional information in children with reflux nephropathy, it does not currently have a role in the usual diagnostic algorithm or follow-up of such children.

Ultrasonography

Sonogram of a large, obstructing ureterocele in a patient with vesicoureteral reflux. The thin rim of the ureterocele is best noted on the inferior most aspect of the bladder. This ureterocele measured 4 cm in greatest dimension and is outlined by contrast material in Image 4. Note the dilated, left-sided refluxing ureter.

Voiding cystourethrogram (VCUG) demonstrates a large, smooth, central filling defect peripherally outlined by contrast material. The catheter is deviated to the patient's right. This finding is consistent with a large ureterocele.

Voiding cystourethrogram (VCUG) demonstrates high-grade IV vesicoureteral reflux in a patient with a duplicated collecting system.

Transverse sonogram in a boy with grade V vesicoureteral reflux and posterior urethral valves. Image demonstrates a thickened bladder wall.

Renal sonogram in a patient with high-grade vesicoureteral reflux secondary to a posterior urethral valve demonstrates moderate hydronephrosis and cortical thinning.

Sonogram of the right kidney in a patient with grade V vesicoureteral reflux. Hydronephrosis and increased echogenicity indicating renal dysplasia secondary to reflux nephropathy. This kidney measured 6.7 cm, while the left one measured 8.3 cm.

Transverse sonogram of the bladder demonstrates left ureteral dilatation near the level of the ureteral insertion.

Longitudinal sonogram demonstrates dilatation of the mid aspect of the ureter. The ureter could be visualized in its entirety and was dilated throughout.

Longitudinal sonogram of the left kidney in a patient with grade V vesicoureteral reflux and a duplex collecting system. There is hydronephrosis of the lower pole moiety and dilatation of the proximal ureter. The upper pole of the kidney was normal on ultrasonography and did not demonstrate reflux on voiding cystourethrography (VCUG).

Findings

The widespread use of prenatal sonography has produced a marked increase in the early detection of urinary-tract pathology in infants. The most common conditions identified are hydronephrosis and hydroureteronephrosis. Hydronephrosis is most often transient, but primary VUR is found in 10-40% of prenatally detected cases of hydronephrosis.

Prenatally detected primary vesicoureteral reflux (VUR) is found in males (male-to-female ratio, 5:1) most of whom have bilateral high-grade reflux.⁸ Low-grade reflux is often associated with other prenatal urologic abnormalities. Mild pelviectasis is seen in 0.5-1% of all pregnancies. The significance of mild pelvic and/or pelvicaliceal dilatation as a marker of VUR is poorly validated but dilatation beyond 15 mm has proven significant and should prompt a thorough search for other urologic abnormalities.

The neonate with sonographic signs of renal pathology and possible reflux should be given prophylactic antibiotics and examined with voiding cystourethrography (VCUG). The risk of renal scarring from neonatal and infant pyelonephritis is too great to ignore.

Generally speaking, ultrasonography is an unreliable modality for the detection of VUR. It cannot be used as the sole means to exclude clinically significant VUR, even when the results are normal. Nevertheless, clues to the presence of VUR can be inferred from certain sonographic findings, namely complete duplication, peristaltic ureteral dilatation and calyceal dilatation. Sonographic measurement of kidney size is an important aspect of the screening examination. An abnormally small kidney in the child suggests parenchymal thinning, even in the absence of visible scar.

Ultrasonography is best used in conjunction with screening VCUG to assess for renal size; upper tract abnormalities, such as hydronephrosis and ureteral dilatation (see Images 13, 25-28); obvious scarring; ureteral ectopia or bladder abnormalities, such as ureterocele (see Images 2-3); and bladder wall thickening (see Images 23-24).

Degree of Confidence

Obtaining reproducible sonograms is highly operator dependent. Full assessment of the bladder and urethra can sometimes be difficult. Smaller scars are less well visualized with sonography than with technetium-99m dimercaptosuccinic acid (DMSA) or glucoheptonate (GH) cortical scanning.

Sonography has been proposed for following up of patients with reflux or for detecting reflux in siblings. New techniques involve instilling carbonated solutions or sonicated albumin into the bladder. Presently, the false-negative rate associated with this procedure is high, and it is not recommended as a routine test for VUR.

False Positives/Negatives

Approximately 74% of kidneys with reflux at VCUG were normal on sonograms obtained on the same day, and approximately 25% of the refluxing kidneys that are missed have reflux of grade III or worse.

The results of sonographic evaluation for hydronephrosis or pelvicaliceal dilatation may vary greatly between the second and third trimesters. Abnormalities may not be detectable until the third trimester, later than the common second trimester screening examination.

Nuclear Imaging

Dimercaptosuccinic acid (DMSA) scans demonstrate photopenia at the right superior pole consistent with scarring in this patient with vesicoureteral reflux.

Nonenhanced CT scan at a level just above ureteral insertion demonstrates bilateral, markedly dilated ureters in a patient with grade V vesicoureteral reflux.

Findings

Direct radionuclide cystography with a^99m Tc-labeled agent (sulfur colloid, diethylenetriamine penta-acetate [DTPA], or pertechnetate) is a well-accepted alternative to fluoroscopic VCUG for screening asymptomatic siblings or offspring, for follow-up examination of children with vesicoureteral reflux (VUR), for postoperative evaluation after ureteral reimplantation, and for excluding VUR when it is not seriously considered (especially in girls).

The advantages of this study include continuous monitoring and imaging, high sensitivity, and a decreased radiation dose for a voiding imaging study. The dose to the pelvic organs was much more significantly lower when the study was popularized in the screen film cassette spot film era of former fluoroscopic equipment. With modern digital fluoroscopy units that reduce dose by pulsed fluoroscopy or other dose reduction strategy combined with video frame grabbing spot images, the dose reduction advantage of the isotope cystogram is only marginal.

Patients with VUR are typically followed up with serial radionuclide cystography every 12-24 months. The International Classification of Reflux is not commonly applied to radionuclide studies, but the amount of activity that appears in the upper urinary tracts can be quantified into 1 of 3 levels of severity and used as a basis of comparison in serial follow-up examinations (see Image 19).

The indirect radionuclide cystogram (no catheterization) using^99m Tc mercaptoacetyltriglycine (MAG3) can be performed in the toilet-trained child, but its specificity is decreased. It is not recommended as a routine screening procedure for evaluating VUR.

The most accurate evaluation of renal scarring and renal function is performed with intravenously injected^99m Tc DMSA or GH. DMSA accumulates in the distal tubular cells and provides excellent visualization of the renal cortex, correlating with histopathologic findings in 95% of experimental animals.

Single photon emission computed tomography (SPECT) is superior to planar imaging techniques, especially in children younger than 3 years. Renal scars detected with DMSA scintigraphy appear as focal or generalized areas of diminished radioisotope uptake associated with loss or contraction of functioning renal cortex. This may appear as thinning or flattening of the cortex in some kidneys, while in others renal scars appear as classic discrete wedge-shaped parenchymal defects (see Image 20).

About 63-75% of patients with acute inflammatory changes on the initial DMSA renal scans do not have VUR, and reflux is present in only 25-50% of kidneys that develop new renal scarring. Although not a prerequisite for acquired renal scarring, VUR is still a risk factor that cannot be discounted and should be evaluated.

Degree of Confidence

Direct radionuclide cystography (continuous monitoring) is more sensitive than VCUG. It can depict as little as 1 mL of refluxed urine and exposes the patient to less radiation.

Grade I reflux affects the ureter only, grade II reflux involves the kidney with no pelvic dilatation, and grade III reflux is reflux with pelvic dilatation (see Image 19).

Renal cortical scintigraphy demonstrates twice as many scars as sonography and 4 times as many scars as EU.

False Positives/Negatives

Any reflux is abnormal.

^99m Tc pertechnetate may be systemically absorbed through an inflamed bladder wall.

If a DMSA or GH study is being performed to detect reflux nephropathy with scar formation, it should be undertaken at least 6 months after a documented UTI because an upper-tract infection causes an abnormal appearance on DMSA or GH scans. Abnormalities resulting from infection are transient, whereas scars result in a permanent abnormality.

In the setting of acute infection, granulocyte aggregation, complement activation, and compression of the renal microcirculation from interstitial edema cause ischemia. Overall, the effect is of reduced regional blood flow and radiotracer uptake. Although this may be a transient phenomenon, it cannot be distinguished from scarring in the acute setting.

Intervention

Intervention for VUR remains a controversial topic. Guidelines for medical and surgical management are constantly being reassessed. For many years, the emphasis on the investigation of the child with UTI has centered on diagnosis of VUR. More recently, some authors have suggested that the focus should be whether the child has renal scarring or is at risk for renal scarring. The natural tendency for VUR to resolve spontaneously during childhood warrants initial medical management of most patients with low-grade reflux. Image 31 shows the usual treatment algorithm of one well-known children's medical center.

Vesicoureteral reflux assessment and treatment algorithm.

The requirement for early postnatal surgical intervention is virtually confined to relieving outflow obstruction (usually boys with posterior urethral valves) and relieving gross hydronephrosis.

Surgical correction of reflux and ureteral reimplantations involve the development of an adequate length of submucosal ureter as it courses into the bladder (see Image 30). It may take several months for inflammatory changes to resolve and the antireflux 1-way mechanism to become competent. The incidence of persistent VUR requiring repeat surgery is between 1% and 3%, usually the result of a short submucosal tunnel or unrecognized neuropathic bladder.

Excretory urogram demonstrates the position of surgically reimplanted ureters after correction of vesicoureteral reflux.

Other surgical techniques include endoscopic submucosal injection of materials to effect bulking of either the subureteric space or proximal ureter resulting in coaptation. Teflon has been the most widely used and studied agent, though reports of granulomas, particle migration, and embolization have curtailed its use in the United States. Other materials include biodegradable glutaraldehyde cross-linked bovine collagen (GAX-collagen), Macroplastique particles, polyvinyl alcohol, and autologous materials such as fat.

Bladder training and techniques to avoid constipation may also be considered to lessen VUR.

Medicolegal Pitfalls

• Voiding dysfunction should be excluded.

Special Concerns

• The results of sonographic evaluation for hydronephrosis or pelvicaliceal dilatation may vary greatly between the second and third trimesters.
  • Abnormalities may not be detectable until the third trimester, later than the common second trimester screening examination.
  • In the prenatal period, VUR is detected more frequently in boys than in girls, with a male-to-female of 5:1.
  • Low-grade reflux is often associated with other prenatal urologic abnormalities.
  • Mild pelviectasis is seen in 0.5-1% of all pregnancies.
  • The widespread use of prenatal sonography has produced a marked increase in the early detection of urinary tract pathology in infants.
  • The most common conditions identified are hydronephrosis and hydroureteronephrosis. Hydronephrosis is most often transient, but primary VUR is found in 10-40% of prenatally detected cases of hydronephrosis.
• With the advent of prenatal sonographic screening, the evaluation for hydronephrosis, and subsequently VUR, is being performed in the neonatal period.
  • The neonate with sonographic signs of renal pathology and possible reflux should be given prophylactic antibiotics and undergo VCUG.
  • The risk of renal scarring from neonatal and infant reflux of infected urine is too great to ignore.

Multimedia

Media file 1: Transverse gray-scale sonogram demonstrates a small left ureterocele in a patient with a low-grade vesicoureteral reflux. Ultrasonography may be the most helpful means to evaluate a patient for a ureterocele, as this is often difficult to visualize on early filling of the bladder during voiding cystourethrography. Patients with gross anatomic abnormalities of the urinary tract are not likely to improve without corrective surgery. In this case, the ureterocele measured less than 1 cm in all dimensions and appeared intermittently throughout the examination.

Media file 2: Sonogram of a large, obstructing ureterocele in a patient with vesicoureteral reflux. The thin rim of the ureterocele is best noted on the inferior most aspect of the bladder. This ureterocele measured 4 cm in greatest dimension and is outlined by contrast material in Image 4. Note the dilated, left-sided refluxing ureter.

Media file 3: Voiding cystourethrogram (VCUG) demonstrates a large, smooth, central filling defect peripherally outlined by contrast material. The catheter is deviated to the patient's right. This finding is consistent with a large ureterocele.

Media file 4: Excretory urogram demonstrates the classic cobra-head appearance of a ureterocele.

Media file 5: Voiding cystourethrogram (VCUG) demonstrates a posterior urethral valve.

Media file 6: Voiding cystourethrogram (VCUG) shows grade I left VUR. Incidentally noted is vaginal reflux.

Media file 7: Voiding cystourethrogram (VCUG) demonstrates grade II VUR into the upper-pole moiety of a duplex collecting system and grade III VUR to the lower-pole moiety.

Media file 8: Grade II vesicoureteral reflux in a patient with ureteral duplication.

Media file 9: Voiding cystourethrogram (VCUG) demonstrates bilateral grade III reflux. The renal pelvis is mildly dilated on the right. There is some mild blunting of the calyceal fornices and loss of papillary impressions in the upper poles bilaterally.

Media file 10: Voiding cystourethrogram (VCUG) of lower ureter and ureterovesical junction in a patient with grade III reflux. The ureteral insertion on the left is between the 3- and 6-o'clock positions. There is a small bladder diverticulum at the ureteral insertion.

Media file 11: Voiding cystourethrogram (VCUG)demonstrates bilateral grade III vesicoureteral reflux.

Media file 12: Longitudinal sonogram corresponding to a voiding cystourethrogram (VCUG) of a grade III vesicoureteral reflux. Note the mild pelviectasis. The degree of pelviectasis or caliectasis does not correlate with the degree of reflux seen on the VCUG.

Media file 13: Voiding cystourethrogram (VCUG) demonstrates high-grade IV vesicoureteral reflux in a patient with a duplicated collecting system.

Media file 14: Grade III vesicoureteral reflux and periureteral-type diverticulum.

Media file 15: Voiding cystourethrogram (VCUG) of the left kidney demonstrates grade V vesicoureteral reflux.

Media file 16: Voiding cystourethrogram (VCUG) demonstrates a tortuous, dilated ureter in a patient with grade V vesicoureteral reflux.

Media file 17: Unilateral grade V vesicoureteral reflux secondary to a posterior urethral valve. There is gross dilatation of the renal pelvis and calyces. Papillary impressions are not visible. Gross intrarenal reflux is also identified.

Media file 18: Nuclear cystograms demonstrate grade III reflux. Reflux to the left kidney is shown, with dilatation of the renal pelvis.

Media file 19: Dimercaptosuccinic acid (DMSA) scans demonstrate photopenia at the right superior pole consistent with scarring in this patient with vesicoureteral reflux.

Media file 20: Nonenhanced CT scan at a level just above ureteral insertion demonstrates bilateral, markedly dilated ureters in a patient with grade V vesicoureteral reflux.

Media file 21: Nonenhanced CT scan in a 12-year-old boy demonstrates marked hydronephrosis and cortical thinning in a patient with grade V vesicoureteral reflux and a history of a posterior urethral valve. Note the free fluid in the pararenal space consistent with forniceal rupture after minor trauma to the abdomen (from football practice).

Media file 22: Sagittal sonogram of the bladder. A Foley catheter is surrounded by thickened, hypertrophied bladder wall, the sequelae of posterior urethral valves in this boy with bilateral grade V vesicoureteral reflux. Note the dilated right ureter.

Media file 23: Transverse sonogram in a boy with grade V vesicoureteral reflux and posterior urethral valves. Image demonstrates a thickened bladder wall.

Media file 24: Renal sonogram in a patient with high-grade vesicoureteral reflux secondary to a posterior urethral valve demonstrates moderate hydronephrosis and cortical thinning.

Media file 25: Sonogram of the right kidney in a patient with grade V vesicoureteral reflux. Hydronephrosis and increased echogenicity indicating renal dysplasia secondary to reflux nephropathy. This kidney measured 6.7 cm, while the left one measured 8.3 cm.

Media file 26: Transverse sonogram of the bladder demonstrates left ureteral dilatation near the level of the ureteral insertion.

Media file 27: Longitudinal sonogram demonstrates dilatation of the mid aspect of the ureter. The ureter could be visualized in its entirety and was dilated throughout.

Media file 28: Longitudinal sonogram of the left kidney in a patient with grade V vesicoureteral reflux and a duplex collecting system. There is hydronephrosis of the lower pole moiety and dilatation of the proximal ureter. The upper pole of the kidney was normal on ultrasonography and did not demonstrate reflux on voiding cystourethrography (VCUG).

Media file 29: Voiding cystourethrogram (VCUG) show a large, distended bladder with irregular and trabeculated margins. This patient had posterior urethral valves.

Media file 30: Excretory urogram demonstrates the position of surgically reimplanted ureters after correction of vesicoureteral reflux.

Media file 31: Vesicoureteral reflux assessment and treatment algorithm.

References

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Keywords

vesicoureteral reflux, VUR, reflux nephropathy, posterior urethral valves, urinary tract infection, UTI

Contributor Information and Disclosures

Author

Kevin F McCarthy, MD, Staff Physician, Department of Radiology, National Naval Medical Center
Kevin F McCarthy, MD is a member of the following medical societies: American College of Radiology and Radiological Society of North America
Disclosure: Nothing to disclose.

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
Veronica Rooks, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Association of Program Directors in Radiology, Radiological Society of North America, and Society for Pediatric Radiology
Disclosure: Nothing to disclose.

Medical Editor

Henrique M Lederman, MD, PhD, Consulting Staff, Department of Radiology, LeBonheur Children's Medical Center and St Jude Children's Research Hospital; Professor of Radiology and Pediatric Radiology, Chief, Division of Diagnostic Imaging in Pediatrics, Federal University of Sao Paulo, Brazil
Henrique M Lederman, MD, PhD is a member of the following medical societies: Society for Pediatric Radiology
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Resolution Imaging Medical Corporation
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

Eugene C Lin, MD, Consulting Radiologist, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine
Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, and Society of Nuclear Medicine
Disclosure: Nothing to disclose.

Related eMedicine topics

Vesicoureteral Reflux (Pediatrics: surgery)

Vesicoureteral Reflux (Urology)

Reflux Nephropathy

Pyelonephritis, Chronic

Radiographic Evaluation of the Pediatric Urinary Tract

Clinical guidelines

Vesicoureteric reflux (VUR). In: Guidelines on paediatric urology.
European Association of Urology - Medical Specialty Society
European Society for Paediatric Urology - Medical Specialty Society. 2008 Mar. 6 pages. NGC:006510

Urinary tract infections in children. In: Guidelines on the management of urinary and male genital tract infections.
European Association of Urology - Medical Specialty Society. 2008 Mar. 13 pages. NGC:006488

ACR Appropriateness Criteria® urinary tract infection—child.
American College of Radiology - Medical Specialty Society. 1999 (revised 2006). 7 pages. NGC:005552

Clinical trials

Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)

Determination of Voiding Patterns of Children With Vesicoureteral Reflux

Evaluation of the Efficiency of Autologous Adipocytes Graft in Endoscopic Treatment in Vesico-Renal Reflux in Children

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