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Pediatric Vesicoureteral Reflux Workup

  • Author: Caleb P Nelson, MD, MPH; Chief Editor: Marc Cendron, MD  more...
 
Updated: May 31, 2016
 

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.

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Imaging Studies

Imaging is the basis of diagnosis and management of vesicoureteral reflux (VUR). The standard imaging tests include renal and bladder ultrasonography 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 prenatally identified hydronephrosis should be evaluated postnatally. Ultrasonography 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 ultrasonography. 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 ultrasonography should not be considered an accurate screening test for findings that would be identified on VCUG.[9]

Although the 2011 AAP guidelines recommended that ultrasonography alone should be the initial screening test for children after UTI, the Society for Pediatric Urology continued to recommend that both ultrasonography 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.[10] 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.[11]

The criterion standard in diagnosis of VUR is VCUG. 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[2] :

  • 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 the renal ultrasonography 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 ultrasonography does not exclude VUR. Only VCUG or nuclear cystography can reliably exclude VUR.

The primary radiopharmaceutical used with renal scintigraphy in the setting of pyelonephritis and vesicoureteral reflux 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 vesicoureteral reflux. 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.

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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.

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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.[12] 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.

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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.

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Contributor Information and Disclosures
Author

Caleb P Nelson, MD, MPH Assistant Professor of Surgery (Urology), Department of Urology, Harvard Medical School; Consulting Staff, Department of Urology, Children's Hospital Boston

Caleb P Nelson, MD, MPH is a member of the following medical societies: American Urological Association, Endourological Society, Phi Beta Kappa, Society for Pediatric Urology, Society for Fetal Urology

Disclosure: Nothing to disclose.

Coauthor(s)

Harry P Koo, MD Chairman of Urology Division, Director of Pediatric Urology, Professor of Surgery, Virginia Commonwealth University School of Medicine, Medical College of Virginia; Director of Urology, Children's Hospital of Richmond

Harry P Koo, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, American Urological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Martin David Bomalaski, MD, FAAP Pediatric Urologist, Alaska Urology; Clinical Assistant Professor, Seattle Children's Hospital

Martin David Bomalaski, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Urological Association

Disclosure: Nothing to disclose.

Chief Editor

Marc Cendron, MD Associate Professor of Surgery, Harvard School of Medicine; Consulting Staff, Department of Urological Surgery, Children's Hospital Boston

Marc Cendron, MD is a member of the following medical societies: American Academy of Pediatrics, American Urological Association, New Hampshire Medical Society, Society for Pediatric Urology, Society for Fetal Urology, Johns Hopkins Medical and Surgical Association, European Society for Paediatric Urology

Disclosure: Nothing to disclose.

Additional Contributors

Bartley G Cilento, Jr, MD Instructor, Department of Surgery, Division of Urology, Children's Hospital of Boston and Harvard Medical School

Bartley G Cilento, Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Urological Association, Massachusetts Medical Society

Disclosure: Nothing to disclose.

References
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  16. De Badiola FI, Soria R, Vagni RL, Ormaechea MN, Moldes JM, Benmaor C. Results of Treatment of Grades IV and V Vesicoureteral Reflux with Endoscopic Injection of Polyacrylate Polyalcohol Copolymer. Front Pediatr. 2013. 1:32. [Medline].

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