Pediatric Vesicoureteral Reflux 

Updated: Jul 09, 2020
Author: Caleb P Nelson, MD, MPH; Chief Editor: Marc Cendron, MD 

Overview

Practice Essentials

Vesicoureteral reflux (VUR), or the retrograde flow of urine from the bladder into the ureter, is an anatomic and functional disorder that can result in substantial morbidity, both from acute infection and from the sequelae of reflux nephropathy.

Signs and symptoms

Most children with VUR present in two distinct groups: those with hydronephrosis and those with clinical urinary tract infection (UTI). Hydronephrosis is often identified antenatally by means of ultrasonography (US). These children typically progress through evaluation and treatment in the absence of clinical illness.

Even for experienced pediatricians, the diagnosis of UTI in children can be difficult, for the following reasons:

  • Children often present with nonspecific signs and symptoms; infection in infants can manifest as failure to thrive, with or without fever; other features include vomiting, diarrhea, anorexia, and lethargy
  • Older children may report voiding symptoms or abdominal pain
  • Pyelonephritis in young children is more likely to manifest as vague abdominal discomfort rather than as the classic flank pain and tenderness observed in adults
  • The presence of fever, while highly suggestive of pyelonephritis, is not reliable enough to lead to the diagnosis
  • Children occasionally present with advanced reflux nephropathy manifesting as headaches or congestive heart failure from untreated hypertension or with uremic symptoms from renal failure

A small group of children without evidence of UTI present with symptoms of sterile reflux, which can include flank or abdominal pain before or during voiding, as well as double voiding or incomplete emptying resulting from delayed drainage of urine out of the upper tracts.

As with the history, few findings on physical examination suggest VUR or UTI. Fever, flank or abdominal tenderness, or an enlarged palpable kidney may be present.

See Clinical Presentation for more detail.

Diagnosis

Diagnosis of UTI depends on obtaining accurate urine culture findings. Although the white blood cell (WBC) count, serum levels of C-reactive protein (CRP), and other blood tests are often used to assist with the diagnosis, no laboratory tests can reliably distinguish cystitis from pyelonephritis. However, other laboratory tests have the following uses:

  • Serum chemistries are used to assess for baseline renal function
  • A complete blood count (CBC) can assist in tracking the response to treatment
  • Urinalysis helps determine if proteinuria is present, which possibly indicates renal impairment

Imaging studies are the basis of diagnosis and management of VUR. The standard imaging tests include renal and bladder US and voiding cystourethrography (VCUG). Indications for imaging studies are as follows:

  • Imaging after the first UTI is indicated in all children younger than 5 years, children of any age with febrile UTI, and boys of any age with UTI
  • Children with antenatally identified hydronephrosis should be evaluated postnatally; however, US performed during the first 3 days of life may have a high rate of false-negative results because of relative dehydration during the neonatal period

Although the traditional approach in children with UTI has been evaluation for VUR with VCUG or radionuclide cystography (RNC), some authorities now advocate that children with a history of febrile UTI undergo a dimercaptosuccinic acid (DMSA) renal scan, to assess for evidence of kidney involvement, kidney scarring, or both; if DMSA scan findings are positive, VCUG is recommended.

One approach is to perform RNC as the initial screening test in girls and then to perform standard VCUG when VUR is observed. Other clinicians use VCUG for the initial diagnosis and use RNC for follow-up studies. The 2011 American Academy of Pediatrics (AAP) guidelines for management of UTI in children aged 2-24 months recommended that VCUG not be performed after an initial febrile UTI.[1]

Voiding cystourethrography

VCUG is the criterion standard in diagnosis of VUR, providing precise anatomic detail and allows grading of the reflux.[2] The International Classification System for VUR is as follows[3] :

  • Grade I - Reflux into nondilated ureter
  • Grade II - Reflux into renal pelvis and calyces without dilation
  • Grade III - Reflux with mild to moderate dilation and minimal blunting of fornices
  • Grade IV - Reflux with moderate ureteral tortuosity and dilation of pelvis and calyces
  • Grade V - Reflux with gross dilation of ureter, pelvis, and calyces, loss of papillary impressions, and ureteral tortuosity

In general, VCUG should be performed after the child has fully recovered from the UTI. However, some children demonstrate reflux only during an episode of cystitis.

Radionuclide cystography

  • Instillation of technetium-99m pertechnetate into the bladder and observation with a gamma camera is a highly sensitive test for VUR
  • Advantages include substantially lower radiation doses than with VCUG and the potential for increased sensitivity because of the ability to conduct prolonged periods of observation
  • Disadvantages primarily consist of the poor anatomic detail, especially of the male urethra
  • Grade I reflux is poorly detected by this study, because the distal ureters are commonly obscured by the bladder
  • Grading by nuclear cystography is limited to mild, moderate, and severe grades.

See Workup for more detail.

Management

General principles of management in children with known VUR are as follows[4] :

  • Spontaneous resolution of VUR is common in young children but is less common as puberty approaches
  • Severe reflux is unlikely to spontaneously resolve
  • Sterile reflux, in general, does not result in reflux nephropathy
  • Long-term antibiotic prophylaxis in children is safe
  • Surgery to correct vesicoureteral reflux is highly successful in experienced hands

Surveillance

  • Still frequently used among older children with vesicoureteral reflux, especially boys who have never had a UTI
  • Children with low-grade VUR, especially those who have never had a UTI, are sometimes followed on surveillance without antibiotic prophylaxis
  • Infrequently used among those with high-grade VUR; antibiotic prophylaxis is usually well tolerated, and there are medicolegal concerns regarding the risk of kidney damage while on surveillance

Antibiotic prophylaxis

  • Started once a child has completed treatment of the initial UTI
  • Discontinued if no VUR is seen on imaging studies
  • If VUR is present, prophylactic antibiotics are continued until the VUR resolves or is surgically corrected, or the child grows old enough that prophylaxis is deemed no longer necessary
  • The 2011 AAP guidelines argued that antimicrobial prophylaxis is not effective at preventing UTI in children with VUR and that there is little value in diagnosing UTI because little can be done about it, short of surgery [1] ; however, data from the RIVUR trial called these assumptions into question [5]

Antibiotics are used as follows:

  • The typical dose is one fourth of the therapeutic dose
  • Antibiotics are usually administered as suspensions once daily, typically in the evening to maximize overnight drug levels in the bladder
  • In neonates with antenatally diagnosed hydronephrosis and in infants younger than 8 weeks who have been treated for UTI, the agent of choice is amoxicillin
  • For older children, the most common antibiotics used are trimethoprim-sulfamethoxazole, nitrofurantoin, and penicillins
  • Cephalosporins are used less often

The prophylactic regimen also includes regular follow-up care and imaging (eg, renal ultrasonography and VCUG or nuclear cystography every 12-18 months).

Children with dysfunctional elimination require aggressive bladder and bowel management. In toilet-trained children with recurrent UTI, voiding postponement behaviors, incomplete emptying, and constipation are extremely common and may be much more important etiologic factors than the reflux itself. Anticholinergic medication, in conjunction with timed voiding, may improve symptoms of dysfunctional voiding and reduces the risk of infection in select patients.

Surgical care

Accepted indications for surgical treatment include the following:

  • Breakthrough febrile UTIs despite adequate antibiotic prophylaxis
  • Severe reflux (grade V or bilateral grade IV) that is unlikely to spontaneously resolve, especially if renal scarring is present
  • Mild or moderate reflux in females that persists as the patient approaches puberty, despite several years of observation
  • Poor compliance with medications or surveillance programs
  • Poor renal growth or function or appearance of new scars

Virtually all open antireflux operations involve reconstruction of the ureterovesical junction to create a lengthened submucosal tunnel for the ureter, which functions as a one-way valve as the bladder fills. Dozens of procedures have been described. Options include open antireflux surgery via an extravesical or an intravesical approach and endoscopic antireflux treatment.

See Treatment and Medication for more detail.

Background

Vesicoureteral reflux (VUR), or the retrograde flow of urine from the bladder into the ureter, is an anatomic and functional disorder with potentially serious consequences. It takles either of the following forms:

  • Primary reflux - VUR in an otherwise normally functioning lower urinary tract
  • Secondary reflux - VUR that is associated with or caused by an obstructed or poorly functioning lower urinary tract, such as that observed with posterior urethral valves or a neurogenic bladder

In both conditions, the ureterovesical junction (UVJ) fails to function as a one-way valve, giving lower urinary tract bacteria access to the normally sterile upper tracts. Although VUR has been recognized as an anatomic phenomenon for centuries, it was not until relatively recently that the substantial morbidity and mortality associated with the condition were recognized.

Early studies demonstrated a correlation between reflux and chronic pyelonephritis in paraplegic individuals and a correlation among urinary tract infection (UTI), reflux, and chronic pyelonephritis in children, which suggested that prevention of VUR may result in reduced prevalence of renal complications. The subsequent developments in the medical and surgical management of VUR formed the basis of the evolving field of pediatric urology.

The objectives in the current treatment of VUR are twofold, as follows:

  • The first goal is the prevention of episodes of acute pyelonephritis with its associated morbidity and mortality
  • The second goal is to prevent the scarring of the kidney associated with VUR (reflux nephropathy), which increases the risk of hypertension and renal failure in children and adults with VUR

Controversy persists over the optimal management of VUR, specifically with respect to the timing, technique, and benefits of surgical correction. Guidelines have been published by the American Urological Association (AUA).[6]  (See Guidelines.)

Pathophysiology

After entering the bladder through the muscular hiatus of the detrusor, the normal distal ureter passes through a submucosal tunnel before opening into the bladder lumen via the ureteral orifice. If the length of the submucosal tunnel or its muscular backing is inadequate, the valve mechanism is incompetent, resulting in reflux. Careful anatomic measurements suggest that the ratio of tunnel length to ureteral diameter must be at least 5:1 to prevent reflux. This fundamental observation is the basis for almost all surgical procedures to correct the disorder.

Beyond the fetal stage, anatomic reflux alone rarely produces renal damage. Experiments in pigs have demonstrated renal scarring in sterile refluxing systems; although the kidneys may display scarring, dysplasia, or both in some patients with antenatally identified and presumably sterile reflux, the data overwhelmingly implicate ascending infection and pyelonephritis as the essential causes of reflux nephropathy. Large studies have repeatedly demonstrated a close correlation between the frequency of UTI and the severity of reflux nephropathy in patients with VUR.[1, 7, 4]

Scarring may result from a single episode of pyelonephritis, especially in very young patients. Ransley and Risdon named this occurrence the "big bang" effect.[8] Most scarring tends to occur at the renal poles, where the anatomy of the renal papillae permits backflow of urine into the collecting ducts. This phenomenon is referred to as intrarenal reflux and gives pathogenic bacteria access to the renal tubules.

The subsequent cascade of inflammation, with release of superoxide and other mediators, results in local tissue ischemia and fibrosis. Over time, when enough renal parenchyma is affected, hypertension, renal insufficiency, and renal failure can result. The reason kidneys of children are so susceptible to damage is unclear; this may be due to reduced levels of renal superoxide dismutase in children.

Etiology

The cause of the defect in primary reflux is unknown.

The existence of a strong genetic component is indicated by the high rate of reflux in relatives of patients with reflux, but the mechanism of transmission is not clear. Some investigators favor a polygenic mode of inheritance, whereas others have suggested autosomal or sex-linked transmission with variable penetrance.

The possibility that UTI may cause reflux has also been investigated. Indeed, a subset of patients has been identified in whom reflux was detectable only during an episode of cystitis. However, most authorities think that UTI and reflux are independent variables and that rates of VUR are higher in children with UTI because these children are actively screened for reflux. The cause-and-effect picture is even less clear in children with secondary reflux.

Rates of reflux are likely increased in the setting of congenital bladder outlet obstruction and neurogenic bladder. More than 50% of boys with posterior urethral valves have VUR. Similar results were seen in a series of children undergoing urodynamic studies for neurogenic bladder.

Dysfunctional voiding, with its inherent increase in intravesical pressure, likely also results in reflux, even in otherwise healthy children. Uninhibited bladder contractions, often associated with contraction of the voluntarily controlled external urinary sphincter to prevent wetting, increase intravesical pressure. The combination of high-pressure voiding and VUR increases the risk of pyelonephritis beyond that of the child with low-pressure reflux.

Confounding all of these data is the fact that urodynamic studies on children are difficult to perform and evaluate; this is true especially with infants, in whom normal reference data are sparse. Whether VUR observed in association with voiding dysfunction and obstruction is a direct result of that dysfunction or simply a component of a grossly abnormal urinary tract is not known.

A unique and complex group of children presents with dysfunctional elimination, which consists of a symptom complex heralded by infection, severe constipation, and daytime wetting. Despite the primary urinary tract presentation, the primary focus should be in the management of constipation and bowel habits. A subset of these children have infrequent voiding and incomplete bladder emptying, which further increases the likelihood of UTI.

Epidemiology

United States statistics

The overall prevalence of VUR is unknown because many children are asymptomatic and the invasive testing required for diagnosis is performed only when clinically indicated. Several older reports of imaging studies performed on healthy children prior to oversight by institutional review boards demonstrated rates of 1-2%, but most of these studies were small and failed to clearly characterize their subject populations. The evidence is clear that the prevalence of VUR is higher among children with UTIs (15-70%, depending on age). Among infants antenatally identified with hydronephrosis on ultrasonography (US), approximately one third were postnatally found to have VUR.

The incidence of reflux clearly is influenced by genetic factors, though specific modes of inheritance have yet to be identified. Siblings of children with VUR have a 25-33% risk of also having VUR, whereas offspring of parents with reflux have a 66% incidence (higher in female offspring than male offspring). Even when asymptomatic, these siblings and offspring can have high-grade reflux and often have renal scarring at evaluation.[9]

Screening of asymptomatic siblings and offspring continues to be an area of controversy. Advocates point out that early identification of children with reflux may prevent episodes of UTI and renal scarring, but other authorities feel that screening asymptomatic individuals is likely to result in significant overtreatment of clinically insignificant VUR, with associated morbidity. As a middle ground, some pediatric urologists screen newborn siblings of children with VUR but do not screen their older, asymptomatic siblings.

International statistics

Many large studies have been performed in Europe, where the prevalence of VUR is estimated to be similar to that in the United States. Disease frequency in other parts of the world is not well described but has been shown to be lower in people of West African descent.

Age-related demographics

VUR is more common among infants and progressively resolves in a substantial proportion of children; thus, prevalence decreases as children age. One study of patients who presented with UTI reported prevalence figures of 70% in patients younger than 1 year, 25% in patients aged 4 years, 15% in those aged 12 years, and 5.2% in adult patients.[7]

Sex-related demographics

UTIs are more common in females, as one might expect from the anatomic differences. This leads to greater screening and, therefore, diagnosis of VUR in females. However, among all children with UTI, boys are more likely to have VUR than girls are (29% of males vs 14% of females). Boys also tend to have higher grades of VUR diagnosed at younger ages, but their reflux is more likely to resolve.

Race-related demographics

Reflux is more common in white children than in those of other races. This disparity extends to children with antenatal hydronephrosis. The editor of this article reviewed his antenatal registry of 1019 patients with antenatal hydronephrosis and found a 15% incidence of VUR in African American patients enrolled in the registry. Although VUR is less common in black children, screening is still recommended after a single UTI in this population. Because little is known about the specific genetic linkage of VUR and because of the wide variation of genes with intermarriage, excluding any group from evaluation is difficult.

Although VUR is much less common in other ethnic groups, the range of severity and rate of spontaneous resolution (grade for grade) are similar between the races.

Prognosis

With modern antibiotics and supportive care, mortality from acute pyelonephritis in children with VUR is very rare.

Primary reflux

Studies comparing medical management with surgical treatment of primary VUR have demonstrated that both have excellent long-term outcomes if surveillance is conscientious and compliance is good. Rates of reflux nephropathy are similar in the two groups, though surgically treated patients have a lower prevalence of pyelonephritis. Studies of adults with childhood reflux and children presenting to a pediatric nephrology clinic have shown that the prevalence of reflux nephropathy in these groups is substantially lower than in historical series. Whether this phenomenon is a result of aggressive treatment of VUR, changes over time in definitions of reflux nephropathy, or other factors is not known.

Secondary reflux

Treatment of children with secondary reflux continues to pose challenges to pediatricians and urologists. A clear understanding of bladder function is essential. Other children have complex combinations of reflux, obstruction, and bladder and renal dysfunction that require a concerted multidisciplinary approach to achieve the maximum potential benefit of therapy.

Patient Education

Effective education of parents and effective communication with the primary care physician are essential if medical management is to be successful.

Poor compliance and untreated episodes of UTI are likely to lead to reflux nephropathy.

 

Presentation

History

Most children with vesicoureteral reflux (VUR) present in two distinct groups, as follows:

  • The first group presents with hydronephrosis, often identified antenatally via ultrasonography (US); these children typically progress through evaluation and treatment in the absence of clinical illness
  • The second group presents with clinical urinary tract infection (UTI)

Even for experienced pediatricians, the diagnosis of UTI in children can be difficult. Children often present with nonspecific signs and symptoms. Infection in infants can manifest as failure to thrive, with or without fever. Other features include vomiting, diarrhea, anorexia, and lethargy.

Older children may report voiding symptoms or abdominal pain. Pyelonephritis in young children is more likely to manifest with vague abdominal discomfort rather than with the classic flank pain and tenderness observed in adults. The presence of fever, while highly suggestive of pyelonephritis, is not reliable enough to lead to the diagnosis.

Even today, children occasionally present with advanced reflux nephropathy, manifesting as headaches or congestive heart failure from untreated hypertension, or with uremic symptoms from renal failure.

A small group of children without evidence of UTI present with symptoms of sterile reflux, which can include flank or abdominal pain before or during voiding, as well as double voiding or incomplete emptying resulting from delayed drainage of urine out of the upper tracts.

Physical Examination

As with the history, few findings on physical examination suggest VUR or UTI. Fever, flank or abdominal tenderness, or an enlarged palpable kidney may be present. In the absence of reliable historical or physical findings, diagnosis depends on laboratory testing and imaging (see Workup), as well as family history.

Complications

Morbidity associated with VUR is substantial, both from acute infection and from the sequelae of reflux nephropathy.

Changes in renal function

Decreases in urine-concentrating ability (proportional to the degree of reflux) and in glomerular filtration rate (proportional to the degree of renal scarring) have been measured in children with VUR.

Decreased renal and somatic growth

Although renal growth assessment in children is difficult because of imaging variability, several studies have documented smaller kidneys in children with reflux and recurrent infections. Surgery may improve growth rates, but small, scarred kidneys are unlikely to grow. Although early studies suggested that somatic growth is negatively affected in children with reflux, subsequent data showed that carefully monitored, properly treated children with VUR have growth rates within normal ranges. In contrast, children with significant renal insufficiency or end-stage renal disease clearly have decreased growth rates.

Hypertension and renal failure

Reflux nephropathy may be the most common cause of childhood hypertension. Presence of hypertension correlates well with the degree of renal scarring, especially when scarring is bilateral. The mechanism is thought to be elevated renin levels produced by damaged renal tissues.

Although not all scarred kidneys in children with hypertension produce excess renin, resection of renal units in cases where unilateral renal vein renin levels are elevated substantially (ratio >1.5) can result in resolution of hypertension.

Improvements in management may result in decreased rates of hypertension among adults who had childhood reflux.

The most devastating outcome of reflux nephropathy is renal failure. The true incidence of chronic renal insufficiency among refluxing children is uncertain. Older studies consistently attributed 15-30% of renal failure in children and young adults to chronic pyelonephritis and reflux nephropathy. However, one transplant series attributed just 2.2% of cases to chronic pyelonephritis. Most authorities now agree that although renal failure is a devastating complication of VUR, it actually affects only a small minority of children with reflux.

 

DDx

 

Workup

Laboratory Studies

Diagnosis of urinary tract infection (UTI) depends on obtaining accurate urine culture findings. The criterion standard for obtaining urine specimens remains the suprapubic aspiration. Any growth in such a sample should be considered significant. In practice, however, this procedure is rarely done. Urethral catheterization provides substantially better specificity; more than 1000 colony-forming units (CFU)/mL is considered significant for these samples.

In children who are toilet trained, culture of a clean-catch midstream specimen is an acceptable method. Growth of more than 100,000 CFU/mL is a significant finding on a midstream-voided specimen.

The least reliable method (ie, bag collection) is the most common method of obtaining a urine specimen in babies. As many as 10% of specimens grow more than 50,000 CFU/mL with no correlation to the actual presence of infection. A negative culture result is helpful because although bag collection can produce false-positive results, false-negative results are very unlikely. A bag specimen with a positive result requires further investigation with ureteral catheterization. Bag collection should be strongly discouraged.

The 2011 American Academy of Pediatrics (AAP) guidelines specified that both a urinalysis showing pyuria and a culture growing more than 50,000 CFU/mL should be the basis for a diagnosis of UTI.[1] Bag urine specimens were explicitly discouraged by the AAP guidelines.

Although the white blood cell (WBC) count, serum levels of C-reactive protein (CRP), and other blood tests are often used to assist with the diagnosis, no laboratory tests can reliably distinguish cystitis from pyelonephritis. Other laboratory testing should include serum chemistries to assess for baseline renal function. A complete blood count (CBC) can assist in tracking the response to treatment. Urinalysis also helps determine if proteinuria is present, which possibly indicates renal impairment.

Imaging Studies

Imaging is the basis of diagnosis and management of vesicoureteral reflux (VUR). The standard imaging tests include renal and bladder ultrasonography (US) and voiding cystourethrography (VCUG), though numerous studies are available.

Imaging after the first UTI is indicated in all children younger than 5 years, children of any age with febrile UTI, and boys of any age with UTI. In addition, children with antenatally identified hydronephrosis should be evaluated postnatally. US performed during the first 3 days of life may have a high rate of false-negative results because of relative dehydration during the neonatal period.

All children with a history of febrile UTI should undergo kidney and bladder US. This allows assessment of the upper tracts for obstruction, renal anomalies and scarring, and other drainage patterns. It does not, however, effectively evaluate for or rule out VUR, and US should not be considered an accurate screening test for findings that would be identified on VCUG.[10]

Although the 2011 AAP guidelines recommended that US alone should be the initial screening test for children after UTI, the Society for Pediatric Urology continued to recommend that both US and cystography be performed.[1]

Although the traditional approach in children with UTI has been evaluation for VUR with VCUG or radionuclide cystography (RNC), some authorities have advocated a "top-down" approach for children with UTI.[11] In this algorithm, a child with a history of febrile UTI undergoes a dimercaptosuccinic acid (DMSA) renal scan to assess for evidence of kidney involvement, kidney scarring, or both. Negative DMSA scan findings suggest that clinically significant VUR is unlikely, obviating the need for VCUG. However, if DMSA scan findings are positive, VCUG is recommended. The merits of alternative approaches to children with UTI are still discussed.

Using DMSA scintigraphy, one group found that the only independent risk factor for renal scar formation after acute pyelonephritis was the presence of VUR. Reflux grade was significantly associated with the prevalence of renal scarring. VCUG is recommended after the first acute episode of infection is confirmed with DMSA scintigraphy.[12]

The criterion standard in diagnosis of VUR is VCUG.[2] This test provides precise anatomic detail and allows grading of the reflux.

The International Classification System for VUR combines features of systems previously used in Europe and in the United States and comprises the following five grades[3] :

  • Grade I - Reflux into nondilated ureter
  • Grade II - Reflux into renal pelvis and calyces without dilation
  • Grade III - Reflux with mild-to-moderate dilation and minimal blunting of fornices
  • Grade IV - Reflux with moderate ureteral tortuosity and dilation of pelvis and calyces
  • Grade V - Reflux with gross dilation of ureter, pelvis, and calyces, loss of papillary impressions, and ureteral tortuosity

In general, VCUG should be performed after the child has fully recovered from the UTI. Performance of the study during an episode of acute cystitis can result in overestimation of the grade of reflux because of paralysis and laxity of the ureteral musculature by bacterial endotoxin. Conversely, some children demonstrate reflux only during an episode of cystitis.

VCUG provides useful imaging of the urethra in males for evaluation of posterior urethral valves. VCUG provides information in both boys and girls about bladder capacity and emptying and may reveal signs of outlet obstruction, such as bladder trabeculae or diverticula. Standard VCUG is recommended as the initial study in boys.

RNC or nuclear cystography with instillation of technetium (Tc)-99m pertechnetate into the bladder and observation with a gamma camera is a highly sensitive test for VUR .

Advantages of RNC include substantially lower radiation doses and the potential for increased sensitivity because of the ability to conduct prolonged periods of observation. Radiation exposure from RNC is about 10% of the exposure from VCUG with modern digital equipment and digital-spot film recording and is about 1% of the exposure from VCUG with conventional fluoroscopic equipment. Disadvantages primarily consist of the poor anatomic detail, especially of the male urethra. Grade I reflux is poorly detected by this study because the distal ureters are commonly obscured by the bladder. Grading by nuclear cystography is limited to mild, moderate, and severe grades.

One approach is to perform RNC as the initial screening test in girls and then to perform standard VCUG when VUR is observed. Other clinicians use VCUG for the initial diagnosis and use RNC for follow-up studies.

Advances in resolution and the incorporation of Doppler technology into ultrasonography units have made radiation-free screening with ultrasonic cystography an increasingly realistic possibility. These studies look for reversal of flow in the ureter during bladder filling. A series using injection of microbubbles as a contrast agent found a sensitivity of 92% and specificity of 93% compared to VCUG. However, this study has not received widespread acceptance. As with nuclear cystography, the primary disadvantage is the lack of precise anatomic detail, and, despite continuing research, sonographic cystography remains an experimental modality.

The primary purpose of renal US is to assess the kidneys for size, parenchymal thickness, and collecting system dilation. It has largely replaced intravenous urography as the screening test of choice for the upper urinary tract because of the absence of radiation, elimination of contrast reaction risk, and noninvasive technique. Despite these advantages, normal findings on US do not exclude VUR. Only VCUG or nuclear cystography can reliably exclude VUR.

Contrast-enhanced voiding urosonography has been found to be a sensitive, radiation-free imaging method for the diagnosis of VUR,[13] though it may overestimate the incidence of reflux.[14]

The primary radiopharmaceutical used with renal scintigraphy in the setting of pyelonephritis and VUR is Tc-99m–labeled DMSA. This agent is rapidly taken up by proximal renal tubular cells and is an excellent indicator of functioning renal parenchyma. Areas of acute inflammation or scarring do not take up the radiopharmaceutical and are revealed as cold spots on imaging.

DMSA scanning has two principal uses. First, it is used to identify and monitor renal scarring. Patients who are medically treated and develop new or progressive scarring are often considered candidates for surgical correction of VUR. For this reason, some clinicians obtain a baseline DMSA scan at the time of diagnosis, which can be used for comparison with subsequent scans. Second, DMSA scanning can also be used as a diagnostic tool during suspected episodes of acute pyelonephritis. However, DMSA may not reveal abnormalities in every case of febrile UTI, and its use in the acute setting is not well defined.

Although the use of DMSA scans as a diagnostic tool during suspected episodes of acute pyelonephritis is advocated by a number of authorities, identification and monitoring of renal scarring is the more common indication. Patients who are medically treated and who develop new or progressive scarring, even in the absence of clinical infection, may benefit from surgical intervention.

Single-photon emission computed tomography (SPECT) is an evolution of this imaging technology that affords higher resolution and more accuracy in detection of renal scarring.

Other Tests

Urodynamic studies reveal functional abnormalities of the lower urinary tract. Such testing is most important in patients in whom secondary reflux is suspected, such as patients with spina bifida or boys whose VCUG is suggestive of residual posterior urethral valves.

Because antireflux surgery is much less successful in patients with secondary reflux, identifying such patients before proceeding with operative intervention is critical.

The basic test is cystometrography (CMG), during which a catheter with an intrinsic or attached manometer is placed in the bladder and the bladder is filled slowly with fluid while its internal pressure is recorded. The CMG gives information about bladder capacity and leak point, pressures at various stages of filling, and the presence and frequency of uninhibited (involuntary) bladder contractions and compliance (ie, the ability of the bladder to accommodate increasing volume at constant pressure).

Detrusor instability is a common finding among children with reflux, and, in some cases, treatment with anticholinergic medication has resulted in resolution of the reflux.

The technical difficulty of performing urodynamic studies in small children, especially infants, is a significant obstacle.

Procedures

Historically, cystoscopy was considered to be a basic element of evaluation for VUR. The position and shape of the ureteral orifices were thought to correlate with the grade and prognosis. Subsequent data demonstrated that cystoscopic observations do not significantly contribute to the radiographic findings. Cystoscopy is sometimes performed at the time of ureteral reimplant surgery to identify additional anatomic abnormalities, such as ureteral duplication and ureteral ectopia. However, cystoscopy is not needed in the evaluation of reflux.

Some researchers have advocated a specialized test called positional instillation of contrast (PIC) cystography in children who have had clinical pyelonephritis but whose conventional VCUG or RNC findings do not reveal VUR.[15] In PIC cystography, a cystoscope is inserted into the bladder, and a jet of contrast is aimed from the beak of the cystoscope directly at the orifice of the ureter, where it enters the bladder. In some children, radiography reveals reflux of the contrast into the ureter in this situation.

The significance of VUR seen on PIC cystography is highly controversial. Advocates claim that the test can identify occult VUR in children with recurrent infections of unknown origin. Skeptics, however, argue that the test is highly artificial and note that treating such "occult" reflux has not been shown to improve outcomes in children.

To the extent that the PIC cystography has any role, it is in the child with recurrent serious febrile UTIs who has had normal VCUG or RNC findings (preferrably both) and who has been evaluated and treated for bladder and bowel dysfunction.

Histologic Findings

Pathologic evaluation does not play a significant role in the diagnosis of VUR. However, differentiating between chronic pyelonephritis and renal damage from renal dysplasia, a congenital malformation of the renal parenchyma seen in association with VUR, may explain the etiology of renal scarring in some children.

 

Treatment

Approach Considerations

Febrile urinary tract infection (UTI) with signs of pyelonephritis in children with vesicoureteral reflux (VUR) requires admission and also treatment with parenteral antibiotics to prevent renal damage. This is particularly true in children who are dehydrated, unable to retain oral intake, or in a toxic state.

The need for inpatient admission should be based on the clinical assessment at the time of presentation. Many patients with febrile UTI can be managed as outpatients. Children who are severely dehydrated or in a septic state, as well as those for whom there are social concerns regarding whether home caregivers can be relied on to care for the ill child properly and completely, should be admitted.

Hospitalization after open antireflux surgery typically lasts 24-72 hours. It is increasingly common for children to be discharged home the morning after surgery, and some centers are performing these procedures on an outpatient basis. Generally, children are discharged once they tolerate a regular age-appropriate diet, their pain is managed with oral pain medication, and they are active at an age-appropriate level. Endoscopic antireflux surgery is generally performed as an outpatient procedure.

Medical Care

The treatment of children with VUR aims to prevent kidney infection, kidney damage, and the complications of kidney damage. Treatment options include surveillance, medical therapy, and surgical therapy.[6] (See Guidelines.) Walker summarized the general principles of management in children with known VUR as follows[4] :

  • Spontaneous resolution of VUR is common in young children but is less common as puberty approaches
  • Severe reflux is unlikely to resolve spontaneously
  • Sterile reflux, in general, does not result in reflux nephropathy
  • Long-term antibiotic prophylaxis in children is safe
  • Surgery to correct VUR is highly successful in experienced hands

Resolution of reflux is dependent on numerous factors, including age, gender, grade of reflux, laterality, history of UTI, and other factors. Several centers have developed calculators or nomograms to help clinicians predict the probability of resolution within a given time frame (eg, 5 years), though these calculators may yield different results for similar inputs. In general, however, low-grade VUR (grades I-II) has high rates of spontaneous resolution (usually >80%). High-grade VUR, especially grade V, is much less likely to resolve at despite many years of observation.

Surveillance is infrequently used among those with high-grade VUR, for numerous reasons. Although no large randomized trials have been conducted establishing the efficacy of prophylactic antibiotics for preventing either UTI or renal scarring, several decades of clinical practice have demonstrated that antibiotic prophylaxis is usually well tolerated, and clinicians typically would rather provide at least some treatment than offer none at all. Medicolegal concerns about the risk of kidney damage while a patient is under surveillance have likewise limited the use of this approach.

Surveillance is still frequently employed among older children with VUR, especially boys who have never had a UTI. Children with low-grade VUR, especially those who have never had a UTI, are sometimes followed on surveillance without antibiotic prophylaxis.

Initial treatment of the child with a UTI involves supportive care and prompt administration of appropriate antibiotics. Timely institution of antibiotic therapy has been shown to be critical in preventing scar formation in kidneys with pyelonephritis.

Animal studies have demonstrated that permanent renal damage occurs if antibiotics are not started within 72 hours, though other studies indicate an even shorter window of opportunity. For this reason, clinicians must maintain a high index of suspicion for UTI in children.

Medical treatment with prophylactic antibiotics remains the mainstay of initial management of VUR (see Medication). Because VUR spontaneously resolves in most children, medical management allows this natural history to take its course while providing some measure of protection against recurrent UTI and renal injury.

Prophylaxis should be started once a child has completed treatment of the initial UTI (see Medication) and continued at least until imaging reveals VUR. If no VUR is seen, prophylaxis is discontinued. If VUR is present, prophylactic antibiotics are continued until one of the following occurs:

  • VUR resolves
  • VUR is surgically corrected
  • The child grows old enough that prophylaxis is deemed no longer necessary

Virtually all children with a new diagnosis of grade I-IV reflux, as well as some with grade V, are given a trial of medical treatment. This consists of antibiotics administered at one fourth of the therapeutic dosage and regular follow-up care and imaging. A typical routine includes renal ultrasonography (US) and voiding cystourethrography (VCUG) or nuclear cystography every 12-18 months.

Given that a substantial number of children experience spontaneous resolution of VUR (50-85% of cases with grade I-III), medical treatment spares this group the morbidity of surgery while protecting the kidneys from further damage.

Once follow-up imaging demonstrates resolution of VUR, antibiotics are discontinued. The importance of conscientious follow-up care during medical management cannot be overemphasized. Lack of compliance with medications or surveillance imaging may result in progression of reflux nephropathy and renal failure in children who are susceptible.

In boys with persistent VUR who have not had recurrent UTIs, antibiotics are often discontinued as the boys approach puberty. However, because of concerns about future pregnancies, surgery may be recommended in girls approaching puberty who have persistent VUR.

The role of antibiotic prophylaxis in this setting has been challenged. Several studies failed to find any decrease in the incidence of UTIs in children with VUR who take antibiotics. However, these studies had significant flaws that made it difficult to state with certainty that antibiotic prophylaxis is ineffective. Accordingly, the National Institutes of Health (NIH) sponsored a large prospective clinical trial of prophylaxis in an effort to answer this key question.

In 2014, the results of the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) study were published.[5] This large 2-year randomized, controlled trial showed that antibiotic prophylaxis with trimethoprim-sulfamethoxazole was associated with a decrease of approximately 50% in the incidence of recurrent UTI among children with VUR, in comparison with placebo.

No difference in renal scarring was observed between groups (though the RIVUR study was not powered to detect such a difference).[5] There was a significant increase in the frequency of resistant organisms in children on treatment in comparison with placebo, though this finding did not seem to impact outcomes.

Some authors have suggested that continuous low-dose antibiotic prophylaxis may have an adverse effect on growth in children with VUR.[16] However, other large series have found no evidence that prophylaxis impacts weight gain or obesity.[17]

Controversies surrounding antibiotic prophylaxis for UTI notwithstanding, the role of antibiotics in the treatment of acute UTI is not debatable, and failure to institute appropriate therapeutic antibiotics in the setting of pyelonephritis (kidney infection) is associated with permanent renal injury and scarring. Children at risk for such infection, such as those with VUR, need prompt and timely evaluation of possible UTI to prevent such outcomes.

The importance of aggressive bladder and bowel management for dysfunctional elimination cannot be overemphasized. In toilet-trained children with recurrent UTI, voiding postponement behaviors, incomplete emptying, and constipation are extremely common and may be much more important etiologic factors than the reflux itself.

Anticholinergic medication, in conjunction with timed voiding, may improve symptoms of dysfunctional voiding and reduces the risk of infection. Anticholinergic agents should be used in select patients so as not to compound the problems of incomplete bladder emptying or worsening constipation.

Many of these patients benefit from some form of bladder training to achieve balanced, low-pressure voiding with coordinated relaxation of the external sphincter and pelvic floor. Such training may range from simple timed voiding regimens to get the children emptying regularly all the way to formal biofeedback programs to teach and improve pelvic muscle coordination. In children with primary bowel elimination problem, treatment with enemas, dietary changes, and stool bulking agents, in coordination with a pediatric gastroenterologist, is critical for success.

Endoscopic Injection Therapy

The most dramatic change in the treatment of VUR has been the rapid growth in the use of endoscopic treatment. Although these techniques had been used in Europe for many years, it was only after the introduction (and approval by the US Food and Drug Administration) of injectable dextranomer/hyaluronic acid copolymer (DHA) that endoscopic antireflux therapy became widespread in the United States.[18]  The perceived benefits of endoscopic treatments include short procedural time, low morbidity, comparable success rates, and preservation of the option for subsequent open surgical repair.

Some clinicians advocate endoscopic treatment as initial management for newly diagnosed VUR, arguing that immediate antireflux treatment obviates the need for long-term antibiotics and repeated imaging studies. However, such a strategy inevitably results in the overtreatment of a large number of children. VUR spontaneously resolves in most children, and even those with persistent VUR may not have a clinical indication for antireflux procedures. In addition, the true long-term success rates for endoscopic treatment with DHA are still to be determined.

Endoscopic techniques involve injection of a bulking substance into the muscular posterior wall of the ureterovesical junction (UVJ). The resulting bulking effect compresses the ureteral lumen and provides a substitute for the normal muscular backing of the transmural ureter.

Some authors emphasize the importance of creating a large mound or "volcanic" appearance of the bulking agent under the orifice, compressing the orifice into a slit. Other authors have described an intramural injection, in which the distal ureter is distended with a jet of saline from the cystoscope, allowing the injection needle to be advanced into the submucosa of the intramural ureter at the 6 o'clock position.

In general, the rates of success (defined as resolution of VUR on postprocedural imaging) reported for endoscopic treatment have been significantly lower than those reported for open antireflux surgery. A meta-analysis of over 5000 patients undergoing endoscopic treatment with various bulking agents found a success rate of 74% after one injection and 85% after one or more injections.[19]  The success rate among the DHA studies was 69% after one injection.

Most studies of endoscopic treatment have found success rates to be lower in patients with higher grades of VUR (ie, the very patients most likely to need antireflux surgery). The meta-analysis previously mentioned found a success rate of 63% after one injection for grade IV VUR.[19]

Single-center reports have noted significantly higher success rates with DHA, with resolution rates of over 90% with one or more injections at some centers.

Additional bulking agents have been used extensively in Europe, particularly polytetrafluoroethylene (PTFE). Although thousands of patients have undergone treatment with PTFE over the past 30 years, persistent concerns over the safety of this bulking agent have limited its use in the United States.

Other bulking agents that have been reported include autologous fat, blood, and chondrocytes; bovine collagen; and polydimethylsiloxane. Although all have certain advantages, concerns over particle migration, carcinogenesis, and technical handling problems have limited their use.

Polyacrylate polyalcohol copolymer (PPC) has been studied as an alternative bulking agent in Europe and South America.[20, 21, 22] Findings suggest that PPC is associated with higher success rates than DHA, at the cost of a higher risk of UVJ obstruction.

Children who undergo endoscopic antireflux treatment need continued follow-up. They require postprocedural imaging, including VCUG at 3-4 months. Patients should be maintained on antibiotic prophylaxis until resolution of VUR is confirmed.

Studies of endoscopic injection of DHA have found that as many as 25% of children whose VUR was cured on the initial VCUG (at 3-4 months) subsequently had recurrence of VUR on a delayed VCUG (12 months). The reasons for late failure of endoscopic therapy are uncertain but may include reabsorption of the injected material, migration of the injected material, or secondary patient factors such as dysfunctional voiding. Some clinicians recommend additional VCUG at 12-18 months after endoscopic treatment because of concerns over the durability of the DHA implant.

Delayed adverse effects of DHA antireflux therapy appear to be uncommon. However, some studies have observed that the DHA implants can strongly resemble a kidney stone in the distal ureter on computed tomography (CT), apparently because of calcification of the DHA implant. Because many children who undergo DHA injection for treatment of VUR eventually undergo CT for numerous reasons, treating physicians and radiologists must recognize that DHA implants may produce a misleading appearance on CT.

Surgical Care

Open antireflux surgery

The decision to proceed to antireflux surgery is based on many factors, and the medical, social, and emotional needs of the patient and the family must be considered. Accepted indications for surgical treatment include the following:

  • Breakthrough febrile UTIs despite adequate antibiotic prophylaxis
  • Severe reflux (grade V or bilateral grade IV) that is unlikely to resolve spontaneously, especially if renal scarring is present
  • Mild or moderate reflux in females that persists as the patient approaches puberty, despite several years of observation
  • Poor compliance with medications or surveillance programs
  • Poor renal growth or function or appearance of new scars

Virtually all open antireflux operations involve reconstruction of the UVJ to create a lengthened submucosal tunnel for the ureter, which functions as a one-way valve as the bladder fills. Dozens of procedures have been described. Surgery for VUR should be performed by a qualified pediatric urologist who is experienced in multiple techniques, so that the surgical procedure can be tailored to the unique anatomic circumstances of the individual patient.

Although several studies have shown that antireflux surgery decreases the incidence of pyelonephritis, randomized trials of antibiotic prophylaxis versus surgical therapy plus antibiotic prophylaxis have not shown differences in the development of nonfebrile UTI, renal scarring, or renal failure. However, most of these studies were statistically underpowered, and the true benefit of antireflux surgery is still incompletely understood.

Intravesical repair

In the intravesical approach, the bladder is opened anteriorly via a low abdominal incision. The ureters are separated from their attachments to the bladder muscle and connective tissue and repositioned under a submucosal tunnel to create the necessary 5:1 length-to-diameter ratio.

The Politano-Leadbetter procedure, developed in the 1950s, is the prototypical intravesical operation. The ureter is dissected completely free of its attachments and passed through a new muscular hiatus created higher on the bladder wall. The ureter is then passed down through a submucosal tunnel, and the orifice is sutured to the mucosa at its original meatal position. This procedure has a reported success rate of 97-99%.

An evolution of the Politano-Leadbetter procedure is the Cohen cross-trigonal technique, which is probably the most popular intravesical repair performed today. In this repair, the original muscular hiatus is used, but the ureter is dissected from its attachments and pulled across the trigone through a submucosal tunnel, and the meatus is sutured into a new position at the end of the tunnel. Reported success rates with this technique are also in the range of 97-99%.

Extravesical repair

The extravesical approach was developed in an effort to avoid the time and morbidity associated with the cystotomy and ureteral anastomosis required for intravesical repair. It is particularly useful in patients with unilateral reflux.

Developed concurrently in Europe and the United States, the Lich-Gregoire repair approaches the bladder via the retroperitoneum. The ureter is dissected from the detrusor, but the orifice is left intact. A narrow furrow in the detrusor then is created, down to but not disrupting the mucosa, and extended cephalad from the ureteral orifice. The distal ureter is then laid into this furrow and the detrusor closed over it. Although early American results were disappointing, further experience and modifications have demonstrated success rates comparable to those of the standard intravesical techniques.

One complication of the extravesical approach is postoperative urinary retention, which generally resolves spontaneously. Judicious use of a bipolar electrocautery during the posterior bladder dissection can reduce incidence of this complication to less than 5%. Rare reports of permanent voiding dysfunction and retention in patients undergoing bilateral extravesical procedures have led some surgeons to use this technique only for unilateral cases.

Robotic-assisted laparoscopic ureteral implantation

Although open ureteral reimplantation is still the surgical gold standard in the treatment of VUR, there is increasing interest in robotic-assisted laparoscopic ureteral reimplantation (RALUR) as an option.[23, 24]

Diet

Children with frequent UTIs often have concurrent problems with constipation and poor bowel habits. Institution of a bowel program in these children can reduce the frequency of infection. High-fiber diets combined with a stool softener, such as docusate, can improve bowel function and reduce colonic and rectal dilation. For severe cases, daily polyethylene glycol is often used.

Activity

Children with VUR can engage in normal activity. Toilet hygiene, especially proper wiping technique in girls, should be taught to children of appropriate age to reduce the frequency of UTI.

Complications

Obstruction after open antireflux surgery

Most cases of postoperative upper tract obstruction are mild, produce no symptoms, and spontaneously resolve. These cases are due to edema at the ureteroneocystostomy site, blood clots, or mucus causing mechanical obstruction. Cases of severe obstruction often have a delayed presentation (1-2 weeks or longer) and may be associated with flank or abdominal pain, nausea, and vomiting.

US reveals dilation on the affected side, though this can be difficult to assess in patients who had significant dilation preoperatively.

High-grade obstruction is usually due to ischemia of the implanted ureteral segment with resulting fibrosis and stricture. This is a rare complication. Occasionally, patients may present with intermittent obstruction due to kinking of the reimplanted ureter with bladder filling.

Treatment for high-grade obstruction is surgical revision of the obstructed system. Percutaneous nephrostomy for temporary drainage may be required if the patient is symptomatic or in a toxic state.

Persistent vesicoureteral reflux after antireflux surgery

Open surgery

Modern series consistently report success rates greater than 95% for antireflux surgery. When reflux persists postoperatively, initial observation with continued antibiotic prophylaxis is indicated. Reoperation is generally reserved for patients with persisted febrile UTI despite prophylaxis.

A very high percentage of patients in whom surgery has failed have voiding dysfunction. Urodynamic evaluation should be considered in these patients, especially if reoperation is considered. Even so, a substantial majority of patients with reflux at the first postoperative study have complete resolution at the 1-year follow-up point.

Endoscopic surgery

Initial management is often repeat injection. Many investigators report routinely injecting as many as three separate times. Patients in whom multiple injections fail should be reevaluated and treated for causes of secondary VUR. Patients with persistent VUR and indications for surgical correction should proceed to open surgery.

New contralateral vesicoureteral reflux after unilateral antireflux surgery

New onset of VUR in a renal unit that had no VUR on preoperative imaging occurs in 10-32% of patients after open correction and 7-14% of patients after endoscopic correction. In general, the new VUR is thought to be of low grade and may be more likely to resolve spontaneously.[25]

Consultations

Good communication between the urologist and the primary care physician is essential for the effective management of VUR. This is especially true for children being treated medically, in whom regular follow-up care and prompt evaluation and treatment of breakthrough UTI are critical in preventing renal damage.

Involvement of a pediatric nephrologist is indicated for children at risk for or manifesting evidence of reflux nephropathy.

Long-Term Monitoring

Children whose VUR is being managed medically are regularly seen on an annual basis. Routine evaluation includes urinalysis and urine culture, appropriate imaging, and blood pressure measurement. Parents must understand the need for proper evaluation and urine culture if they suspect UTI. In some cases, parents are taught to perform urinalysis at home. Positive home urinalysis results should prompt formal testing at a physician's office.

After surgical correction of VUR, patients are seen in the clinic 2-6 weeks after discharge with renal US or renal scintigraphy to exclude upper tract obstruction. Patients continue taking prophylactic antibiotics until a second return visit 3-6 months postoperatively, at which time VCUG or nuclear cystography is performed.

Some have abandoned the practice of a follow-up VCUG or radionuclide cystography (RNC) after open surgical treatment because success rates are high. Antibiotic therapy is usually stopped after normal postnatal US results are obtained. If VCUG or RNC is performed postoperatively and reveals resolution of reflux, antibiotics are discontinued, and no further invasive studies are necessary unless further febrile UTIs develop.

A study by Arlen et al suggested that routine VCUG is not necessary after endoscopic treatment of pediatric primary VUR with the double HIT (hydrodistention implantation technique) approach.[26] The authors recommended that postoperative VCUG be considered an option rather than a recommendation in this setting unless it is indicated on the basis of high grade, young age, clinical failure, or family or surgeon preference.

Some clinicians continue to observe children with VUR periodically with blood pressure checks and renal US.

 

Guidelines

AUA Guidelines for Management of Pediatric Vesicoureteral Reflux

The American Urological Association (AUA) has issued guideline statements regarding management of vesicoureteral reflux (VUR) in children.[6] Statements are classified as standards, recommendations, or options.

Initial management

Child with VUR aged < 1 year

Continuous antibiotic prophylaxis (CAP) is recommended for the child younger than 1 year of age with VUR and a history of a febrile urinary tract infection (UTI). (Recommendation)

In the absence of a history of febrile UTI, CAP is recommended for the child with VUR grade III-V identified through screening. (Recommendation)

In the absence of a history of febrile UTI, CAP may be offered to the child with VUR grade I-II identified through screening. (Option)

Circumcision of the infant male with VUR may be considered on the basis of the increased risk of UTI in uncircumcised boys. (Option)

Child with UTI and VUR aged >1 year

If clinical evidence of bladder/bowel dysfunction (BBD) is present, treatment of BBD is indicated, preferably before any surgical intervention for VUR is undertaken. (Recommendation)

CAP is recommended for the child with BBD and VUR because of the increased risk of UTI while BBD is present and being treated. (Recommendation)

CAP may be considered for the child with a history of UTI and VUR in the absence of BBD. (Option)

Observational management without CAP, with prompt initiation of antibiotic therapy for UTI, may be considered for the child with VUR in the absence of BBD, recurrent febrile UTI, or renal cortical abnormalities. (Option)

Surgical intervention for VUR, including both open and endoscopic methods, may be used. (Option)

Follow-up management 

General

General evaluation, including monitoring of blood pressure, height, and weight, is recommended annually. (Recommendation)

Urinalysis for proteinuria and bacteriuria is indicated annually, including a urine culture and sensitivity if the urinalysis is suggestive of infection. (Recommendation)

Imaging with cystography and ultrasonography

Ultrasonography (US) is recommended every 12 months to monitor renal growth and any parenchymal scarring. Voiding cystography (radionuclide cystography or low-dose fluoroscopy, when available) is recommended between 12 and 24 months, with longer intervals between follow-up studies in cases where evidence supports lower rates of spontaneous resolution (eg, grade III-V VUR, BBD, and older age). If an observational approach is being used, follow-up cystography becomes an option. (Recommendation)

Follow-up cystography may be done after the age of 1 year in patients with VUR grade I-II. (Option)

A single normal voiding cystogram (ie, no evidence of VUR) may serve to establish resolution. The clinical significance of grade I VUR and the need for ongoing evaluation are undefined. (Option)

Imaging with dimercaptosuccinic acid

Dimercaptosuccinic acid (DMSA) imaging is recommended when renal US is abnormal, when there is a greater concern for scarring (eg, breakthrough UTI [BT-UTI] or grade III-V VUR), or when serum creatinine is elevated. (Recommendation)

DMSA imaging may be considered for follow-up of children with VUR to detect new renal scarring, especially after a febrile UTI. (Option)

Interventions for breakthrough urinary tract infection

If symptomatic BT-UTI occurs (manifested by fever, dysuria, frequency, failure to thrive, or poor feeding), a change in therapy is recommended. The clinical scenario will guide the choice of treatment alternatives; this includes VUR grade, degree of renal scarring (if any), and evidence of abnormal voiding patterns (BBD) that might contribute to UTI, as well as parental preferences. (Recommendation)

It is recommended that patients receiving CAP with a febrile breakthrough UTI be considered for open surgical ureteral reimplantation or endoscopic injection of bulking agents for intervention with curative intent. (Recommendation)

In patients receiving CAP with a single febrile breakthrough UTI and no evidence of preexisting or new renal cortical abnormalities, changing to an alternative antibiotic agent is an option before intervention with curative intent. (Option)

In patients not receiving CAP who develop a febrile UTI, initiation of CAP is recommended. (Recommendation)

In patients not receiving CAP who develop a nonfebrile UTI, initiation of CAP is an option. (Option)

Surgical treatment 

Surgical intervention for VUR, including both open and endoscopic methods, may be used. (Option)

Postoperative imaging for patients receiving definitive interventions

After open surgical or endoscopic procedures for VUR, renal US should be obtained to assess for obstruction. (Standard)

Postoperative voiding cystography following endoscopic injection of bulking agents is recommended. (Recommendation)

Postoperative cystography may be performed after open ureteral reimplantation. (Option)

Follow-up management after resolution

After resolution of VUR, either spontaneously or through surgical intervention, and if both kidneys are normal on US or DMSA scanning, general evaluation (including monitoring of blood pressure, height, and weight) and urinalysis for protein and UTI annually through adolescence are an option. (Option)

After resolution of VUR, either spontaneously or through surgical intervention, general evaluation (including monitoring of blood pressure, height, and weight) and urinalysis for protein and UTI are recommended annually through adolescence if either kidney is abnormal on US or DMSA scanning. (Recommendation)

With the occurrence of a febrile UTI after resolution or surgical treatment of VUR, evaluation for BBD or recurrent VUR is recommended. (Recommendation)

It is recommended that the long-term concerns of hypertension (particularly during pregnancy), renal functional loss, recurrent UTI, and familial VUR in the child's siblings and offspring be discussed with the family and communicated to the child at an appropriate age. (Recommendation)

 

Medication

Antibiotics

Class Summary

These are used for maintenance of sterile urine. Antibiotic agents used for prophylaxis in children with vesicoureteral reflux (VUR) are chosen for their efficacy in the urinary tract, safety, and tolerability. The typical dose is one fourth of the therapeutic dose. They are usually administered as suspensions once daily, typically in the evening to maximize overnight drug levels in the bladder. In neonates with antenatally diagnosed hydronephrosis and in infants younger than 8 weeks who have been treated for urinary tract infection (UTI), the agent of choice is amoxicillin. For older children, the most common antibiotics used are trimethoprim-sulfamethoxazole, nitrofurantoin, and penicillins. The cephalosporins are used less often.

Amoxicillin (Amoxil, Biomox, Trimox)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. Is generally well tolerated, although has a higher rate of fecal resistance than some other agents. Metabolized effectively by newborns, making it a good choice for neonates.

Sulfamethoxazole and trimethoprim (Bactrim, Septra, Cotrim)

Inhibit bacterial growth by inhibiting synthesis of dihydrofolic acid. DOC in children >6-8 wk. The maturing hepatobiliary system is able to process trimethoprim-sulfamethoxazole combination agents, which have an excellent urinary concentration profile and tend to cause fewer fecal resistance problems. Well tolerated orally.

Nitrofurantoin (Furadantin, Macrodantin)

Synthetic nitrofuran that interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations.

Another common urinary antiseptic agent for children >8 wk. Unpleasant taste of the liquid form makes it unacceptable to some children. Older children who can tolerate tablets do well with this medication.