By Scott Williams, MD

April 3, 2002 --

Radionuclide Cystography/Vesicoureteral Reflux

Clinical Findings

Urinary tract infection (UTI) is frequent in children (prevalence of about 5% in infants and young children and 80% of first infections before the age of 2 years) [6]. Girls are affected twice as often as boys [6]. The clinical manifestations of urinary tract infection in the pediatric patient population are frequently nonspecific. Children may present with fever, irritability, poor feeding, failure to thrive, or diarrhea. Older children are usually able to report the more typical complaints of urgency, frequency, and dysuria. The majority of children with a UTI have no anatomic or functional abnormality in their urinary system. UTI, however, can be associated with such a problem- most commonly vesicoureteral reflux (VUR). VUR is diagnosed in 20-30% of children with a first UTI [7]. The majority of pediatric patients who develop renal scars after a urinary tract infection have VUR, and higher grades of reflux are associated with an increase in parenchymal scarring [5]. Because of this, all children with a well documented UTI should have further evaluation of their urinary tract.

Although vesicoureteral reflux is found in less than 1% of the general population, it is seen in up to 35% of children with urinary tract infections. Vesicoureteral reflux is caused by a failure of competency of the valvular function of the normal ureterovesical junction. The normal ureter passes obliquely through the bladder wall and submucosa to its opening at the trigone. The length of the intramural tunnel, especially its submucosal component, with respect to the diameter of the ureter plays a primary role in the competence of the vesicoureteral junction. As the bladder fills with urine, the junction closes by compression like a flap-valve, thus preventing reflux. If the intramural length of the ureter is too short in comparison to its diameter, the valve will not close completely.

Neonates with VUR are generally treated conservatively, because the condition will resolve spontaneously in 45-70% of patients- typically during the first 2 years of life [6]. This occurs because as a child grows, the ureter grows more in length than in diameter. Reflux will cease when the ratio of the length to diameter permits the valve to close. Spontaneous resolution is more common in patients with low grade reflux [6] and it has been shown that reflux is less likely to resolve spontaneously when ureteral dilatation is present. Reflux will resolve spontaneously in about 85% of patients with normal caliber ureters (typically 1 to 3 years), but in only about 40% of those with dilated ureters.

Reflux can be seen in up to 33 to 45% of asymptomatic siblings, and evaluation of the other children in the family is essential. It should also be noted that reflux and obstruction (UPJ) may coexist and delayed clearance of tracer from the collecting system on a retrograde study warrants further investigation.

Surgical correction of reflux should be considered for children over 11 years of age in whom reflux persists, or when infection cannot be controlled with continuous antibiotic prophylaxis.

Reflux can result in 2 forms of renal damage:

Reflux atrophy: Large volume, high pressure reflux alone causes varying degrees of pelvocalyceal system dilatation and global renal wasting. [1] Dr. Majd [Childrens Hospital, Washington, D.C.] feels that reflux without infection probably does not cause significant renal damage.

Infection: Intra-renal reflux can occur due to compound papilla which have round (rather than slit-like) orifices, and thus offer less protection against reflux. This tends to be seen more commonly at the poles. Renal parenchymal infection with resultant scarring can result from this type of reflux. Long term complications include renal insufficiency and hypertension [6].

Grades of Reflux [5]: (Radiologic VCUG)

Grade Findings
I Reflux confined to ureter only
II Reflux to the level of the intrarenal collecting system without dilatation
III Grade II + mild or moderate dilatation of the ureter or renal pelvis, but no or only slight forniceal blunting
IV Grade II + calyceal dilatation and obliteration of the sharp angle of the fornices, but maintainance of the papillary impressions
V Gross dilatation and tortuosity of the ureter; gross dilatation of the renal pelvis and calices; papillary impressions are no longer visible

Grades I-III: Typically resolve as the child grows

Grades IV-V: Typically require surgery to correct

Scintigraphy

Radionuclide cystography permits visualization of very small volumes of reflux, as little as 0.2 ml at a distance of 2 cm from the bladder. It is at least as sensitive, and probably more sensitive than contrast cystography [2]. Despite the fact that minimal reflux in the distal ureter may be missed, the continuous monitoring and the irrelevancy of overlying bowel contents make nuclear cystography very effective for the detection of reflux. Bladder volume at the time of reflux appears to have prognostic significance- if the volume at which reflux occurs increases on annual examination, it may indicate a better likelihood for spontaneous cessation of reflux.

The major disadvantages of radionuclide cystography are:

  1. Its unsuitability for evaluation of the male urethra
  2. Minor bladder wall abnormalities such as small diverticula cannot be detected (although these may not be clinically significant)
  3. Reflux cannot be graded based upon the 5 grade international system (merely as mild, moderate, or severe, which is very subjective).

Cystitis occurring as a result of the procedure is seen only rarely (0.2% of cases).

Bladder filling volume is estimated using the formula:

Vol = (age in years + 2) x 30ml

Volume is typically underestimated in girls.

Procedure:

For a detailed description, see the SNM Nuclear Medicine Procedure Guidelines for Pediatric Cystography (June 1996)

Theoretically, Tc04 or Tc-DTPA could be absorbed across the bladder mucosa (especially if cystitis were present) and the subsequent renal excretion could result in the false-positive diagnosis of reflux. As a result, some investigators recommendusing Tc-SC. In either case, 0.5 to 1 mCi (18.5 to 37 MBq) of tracer is instilled into the bladder with normal saline. The saline bag is placed 1 meter above the table. After adequate filling, oblique projections may be obtained to help detect small amountsof reflux in the distal segment of the ureters. Refilling and revoiding techniques may detect more cases of reflux than the single fill/void technique (particularly low grade reflux). The total dose to the patient depends on the dose used, filling rate, and total filling time (usually about 1 mrad/min. to the bladder wall). Typical ovarian doses are about 5 mrad and testicular doses are about 1 to 2 mrad. For conventional contrast cystography,the dose to the bladder, gonads, and pelvic marrow is at least 75 to 100 mrad. Thus, on the average, the gonadal dose from radionuclide cystography is about one one-hundredth that of standard x-ray studies.

The clinical indications for radionuclide cystography include:

  1. Follow-up exam for patients with known reflux.
  2. Initial screening test for reflux in girls with UTI's.
  3. Screening of asymptomatic siblings.
  4. Serial evaluation of children with neuropathic bladders who are at increased risk for reflux to develop.
  5. Assess of the results of antireflux surgery

Ultrasound: Ureteral dilatation is the US finding with the greastest accuracy for VUR (sensitivity 73% and specificity 88%) [7].

REFERENCES:

(1) Nuclear Medicine Annual 1992; Sfakianakis GN, et al. Scintigraphy in acquired renal disorders. Ed. Freeman LM. Raven Press, Ltd. New York. 157-224

(2) Semin Nucl Med 1993; Eggli DF, Tulchinski M. Scintigraphic evaluation of pediatric urinary tract infection. 23(3):199-218. Review.

(3) Urologic Clinics of North America 1979; Majd M, Belman AB. Nuclear cystography in infants and children. 6: 395-406

(4) Pediatric Annals 1986; Majd M. Radionuclide imaging in clinical pediatrics. 15: 396-408

(5) Radiographics 2002; Berrocal T, et al. Anomalies of the distal ureter, bladder, and urethra in children: embryologic, radiologic, and pathologic features. 22: 1139-1164

(6) J Nucl Med 2006; Boubaker A, et al. Radionuclide investigations of the urinary tract in the era of multimodality imaging. 47: 1819-1836

(7) Radiology 2010; Leroy S, et al. Vesicoureteral reflux in chidlren with urinary tract infection: comparison of diagnostic accuracy of renal US criteria. 255: 890-898


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