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Vesicoureteral Reflux Pediatric Urology

Cordell Davis

on 12 April 2011

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Transcript of VUR

Landmark Studies Medical Management Surgical Management Caused by a fundamental deficiency in the function of the UVJ antireflux mechanism while the remaining factors (bladder and ureter) remain normal or relatively noncontributory
Reflux as a result of the normal function of the UVJ being overwhelmed. Bladder dysfunction of a congenital, acquired, or behavioral nature is frequently the root cause of secondary reflux. It is also accepted that reflux is often considered secondary if its absence was documented at some point before its detection.
I Into a nondilated ureter
II Into the pelvis and calyces without dilatation
III Mild to moderate dilatation of the ureter, renal pelvis, and calyces with minimal blunting of the fornices
IV Moderate ureteral tortuosity and dilatation of the pelvis and calyces
V Gross dilatation of the ureter, pelvis, and calyces; loss of papillary impressions; and ureteral tortuosity
VCUG Bladder contrast is instilled by gravity after urethral catheterization
Static images record bladder contour, the presence of diverticula or ureteroceles, the grade of reflux, the configuration and blunting of calyces, and intrarenal reflux
Delayed or postvoid films are crucial in documenting clearance of contrast from the upper tracts inasmuch as retained contrast, particularly with dilated pelvicalyceal systems, could signify the presence of a concomitant UPJ obstruction.
If both the UPJ and UVJ meet the criteria for operative repair, the UPJ should be repaired first to avoid the incipient obstruction that may ensue if resistance is added to the UVJ when the reflux is corrected
RNC RNC does not provide discrete images of the ureteral and calyceal architecture required to assign reflux grade, classifying reflux by RNC is difficult. RNC has historically enjoyed a reputation for requiring approximate 1% of the radiation exposure generated by a VCUG.
Reduced radiation requirements of modern digital techniques have significantly narrowed the difference between fluoroscopy and RNC. Little anatomic detail is afforded by RNC.
Ideal both as a screening modality and for monitoring the natural history or surgical follow-up of reflux. In contrast to the VCUG, the instilled bladder contrast material, usually technetium Tc 99 pertechnetate, is itself the radiation source.

Reflux is detected by scintigraphic gamma camera images Lack of the confounding imaging densities typical of fluoroscopy, as well as the ability to obtain prolonged exposures, allows for greater sensitivity of RNC in grades II to V reflux. Sonography Nonionizing, noninvasive imaging platform

Serial follow-up of renal growth and development

The impact of any intercurrent febrile UTI can be gauged by observing the effects on renal growth

Images the degree of corticomedullary differentiation Loss of corticomedullary differentiation, or an increase in the overall echogenicity of the kidney, is associated with some degree of renal functional impairment
Loss of corticomedullary differentiation, or an increase in the overall echogenicity of the kidney, is associated with some degree of renal functional impairment Cortical Defects:

Sterile reflux is considered benign.

The youngest patients are at greatest risk for postpyelonephritic renal scarring.

Most scarring probably follows the first episode of pyelonephritis.

Somatic growth is an accurate reflection of renal cortical integrity Description & Natural History Primary Reflux Secondary Reflux The International Reflux Study in Children. Birmingham Reflux Study Smellie et al Capozza and Caione Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) North American (Weiss et al, 1992a) and European (Tamminen-Mobius et al, 1992) cooperative study randomized children younger than 9 years with high-grade reflux to watchful waiting with prophylaxis or corrective open surgery.
Although surgery was complicated by temporary postoperative obstruction in some patients, it was more effective than prophylaxis in reducing, but not eliminating the occurrence of pyelonephritis.
The incidence of UTI (38%) was the same with both modalities.

Both modalities were equally effective in reducing, but not eliminating new scar formation. Only the European arm stratified data for the effect of dysfunctional voiding behavior (18%) (van Gool et al, 1992).

When untreated, voiding dysfunction was associated with more UTIs, more persistent cases of reflux, and greater grade variation during follow-up. Randomized controlled trial (RCT) of severe VUR. Antibiotic prophylaxis vs ureteral reimplantation

No difference in rates of UTI, renal growth, new or progressive scarring after 5 years RCT of children age 1–12 years with bilateral grades III–V VUR with bilateral scarring. Antibiotic prophylaxis vs ureteral reimplantation.

At 4 and 10 years no difference in renal function, rates of hypertension or renal failure, or renal growth in patients treated medically vs ureteral reimplantation RCT of children age >1 year with grades II–IV VUR. Antibiotic prophylaxis vs endoscopic injection of Dx/Ha

More UTIs in the Dx/Ha-treated group. Reflux was resolved in 69% of the Dx/Ha-treated vs 38% treated with prophylactic antibiotics at 1 y Purpose: To learn whether all children with vesicoureteral reflux (VUR) should be treated with antibiotics. The study will tell us if prophylactic antibiotic treatment prevents urinary tract infections and renal scarring in children with VUR. 1 Outcome: Recurrent febrile or symptomatic urinary tract infection during 2-year follow-up Secondary Outcomes Renal scarring based on DMSA scan performed 1 and 2 years after enrollment

Severe renal scarring on outcome scan

Presence of E.coli resistant to TMP/SMZ (based on rectal swab)

Recurrent febrile or symptomatic UTI caused by TMP/SMZ-resistant organism
AUA Guidelines Grading & Imaging Maintaining urinary sterility through the judicious use of single daily low-dose antimicrobial prophylaxis.
Smellie and BT-UTI:
1) If the organism is sensitive to the prescribed prophylactic antibiotic, the child or parent has probably not been compliant or the dose is too low
2) If the organism is resistant to the prescribed antibiotic, either the residual bladder volume is too high too often, or the dose is too high Deflux Politano-Leadbetter Glenn-Anderson Cohen Lich-Gregor Grade of VUR% Success
I 79%
II 79%
III 72%
IV 62% 246 ureters successfully treated endoscopically with Dx/Ha

Retested at 12 months
27% showed recurrent VUR. Most of those that recurred were higher grades (III–V) of VUR. 1) Initial Evaluation of patients with VUR

2) Management of children over one year of age with VUR

3) Evaluation and management of infants with VUR

4) Management of children with VUR and Bladder and Bowel Dysfunction (BBD)

5) Screening of siblings and offspring of patients with VUR

6) Screening of neonates and infants with prenatal hydronephrosis. Standard:
(1) the health outcomes of the alternative interventions are sufficiently well-known to permit meaningful decisions and
(2) there is virtual unanimity among panel members about which intervention is
preferred. Recommendation:
(1) the health outcomes of the alternative interventions are sufficiently well-known to permit
meaningful decisions and
(2) an appreciable, but not unanimous majority of the panel members agrees on which intervention is preferred.

1) the health outcomes of the interventions are not sufficiently well-known to permit meaningful decisions or
2) preferences are unknown or equivocal. R: Urinalysis for proteinuria and bacteriuria is recommended. If the urinalysis indicates infection, a urine culture and sensitivity is recommended.

R: Because VUR and urinary tract infection may affect renal structure and function, performing renal ultrasound to assess the upper urinary
tract is recommended.

O: A baseline serum creatinine may be obtained to establish an estimate of glomerular filtration rate (GFR) for future reference.

O: DMSA (technetium-99m-labeled dimercaptosuccinic acid) renal imaging can be obtained to assess the status of the kidneys for scarring and function. Appropriate approach to the management of the child with VUR and BBD has not been defined.

May be at greater risk of renal injury due to infection.

The presence of untreated BBD can be shown to affect several aspects of VUR. The incidence of breakthrough UTI in children on continuous antibiotic prophylaxis (CAP) is greater in those with BBD than in those without BBD.

In children receiving CAP, resolution rates were 31% for those with BBD and 61% for those without BBD For children treated with open
surgery, the presence of BBD did not appear to alter surgical resolution rates, which were 97% in both groups S: Symptoms indicative of bladder/bowel dysfunction should be sought in the initial evaluation, including urinary frequency and urgency, prolonged voiding intervals, daytime wetting, perineal/penile pain, holding maneuvers (posturing to prevent wetting), and constipation/encopresis. Goals
1) prevent recurring febrile UTIs 2) prevent renal injury
3) minimize the morbidity of treatment and follow-up. R: Continuous antibiotic prophylaxis is recommended for the child less than one year of age with VUR with a history of a febrile urinary tract infection.
This approach is based on the greater morbidity from recurrent urinary tract infections found in this population. Greater likelihood of BBD
Lower probability of spontaneous resolution of VUR
Lower risk of acute morbidity from febrile UTI
Greater ability of the child to verbally complain of symptoms to indicate acute infection
Management decision should be made with recognition of the clinical context, including the presence of BBD, patient age, VUR grade, the presence of scarring, and parental preferences

Associated Abnormalities UPJ PUV BBD UTI Duplication Bladder Diverticuli Renal Anomalies VUR associated with UPJ obstruction ranges from 9% to 18%

High-grade reflux is five times more likely than lower grades of reflux to be associated with UPJ obstruction
1) Pelvis shows little or no filling whereas the ureter is dilated by contras; may indicate a point of kinking secondary to reflux, or it may occur as a result of primary UPJ obstruction itself (image next slide).
2) Contrast that enters the pelvis may be poorly visualized because of dilution in a large pelvic volume, and the pelvis will exhibit markedly reduced radiodensity in comparison to the ureter or bladder.
3) A large pelvis that fails to exhibit prompt drainage but retains contrast Most common anatomic obstruction of the bladder in the pediatric population is posterior urethral valves (PUVs).
Reflux is present in 48% to 70% of patients with PUVs
Relief of PUV obstruction appears to be responsible for resolution of reflux in about a third of patients.
In older children, acquired abnormalities in voiding parameters, commonly known as dysfunctional voiding or dysfunctional elimination, have been associated with reflux. Reflux is not a general cause of UTI.

Reflux facilitates pyelonephritis UTI is present in only 5% of children with fever.

Microbial contamination of bagged specimens is common (useful if the resulting urine culture is negative).

Catheterized specimen is most sensitive (less acurate if preputial skin is not yet retractable) Radiographic investigation for VUR has generally been directed to children younger than 5 years, all children with a febrile UTI, and any male with a UTI regardless of age or fever, unless sexually active.

There is little correlation between the degree of antenatal hydronephrosis and the existence of reflux VUR is the most common abnormality associated with complete ureteral duplication.

The embryologic origin of the duplicated ureter supports the observation that reflux occurs most commonly into the lower pole. Reflux associated with paraureteral diverticula resolves at rates similar to those of primary reflux and should be managed according to the prevailing indications for the reflux itself, irrespective of the diverticulum. The cardinal renal anomalies associated with reflux are multicystic dysplastic kidney (MCDK) and renal agenesis, and the presence of either condition mandates a VCUG. Age & Gender Unilateral vs. Bilateral Bladder Dynamics Grade In patients presenting with UTIs, the majority are female.

VUR presenting as antenatal hydronephrosis: Boys are more commonly affected than girls.

VUR presenting as UTI: female >> male

Boys more often have bilateral and higher grade VUR at presentation.

Breakthrough infections are more common in females than males.

While in general the resolution rates for males and females with a given grade and laterality of VUR are similar, there have been studies that show a slightly better rate for resolution of low-grade VUR in males over time.

Boys with VUR who present in the first year of life have significantly better rates of resolution for high grades (IV and V) compared with older children and females

In predicting early resolution of VUR (within 2 years of diagnosis), age younger than 2 years has been shown to be a significant factor independent of grade. In patients who present with initial unilateral VUR, approximately 10%–20% will be found to have bilateral VUR on subsequent voiding cystourethrogram (VCUG) studies Rarely are bladder dynamics of children with VUR considered or evaluated during the routine evaluation of children with VUR. AUA Reflux Guidelines panel found laterality was only significant for grades III and IV, where the presence of bilateral VUR was significantly less likely to resolve. Bilateral VUR is often reported not to be an important factor in predicting resolution for lower grades of VUR The bladder volume at the onset of VUR or timing of VUR (VUR during filling vs voiding only) are factors that influence the possibility of spontaneous resolution of VUR. Reflux, which occurs either early in filling or at low pressures, should be reflective of a more severe defect at the ureterovesical junction, and thus a lower likelihood for spontaneous resolution. Bladder pressure at the onset of VUR has been shown to be significantly lower in patients with persistent VUR than in those in whom it resolves, independent of grade. VUR, which occurs only during voiding, has a much better chance to resolve than passive VUR during filling. Grading System
Weaknesses Cystoscopy PICC The entire reflux literature itself, which historically reports results in terms of five separate grades, must be considered with some circumspection because the veracity of grade at the time of the contrast study may, to some extent, be arbitrary. Expected concordance between ureteral and calyceal dilation does not always occur It is rare for cystoscopy to add any information that will alter management of a patient with reflux, either at the time of initial diagnosis or during follow-up. Purports to detect reflux under general anesthesia in patients with febrile UTIs but a normal VCUG

Rubenstein et al (2003), 5 of 39 renal units from control patients without infection or bladder abnormalities and with normal VCUGs nevertheless showed reflux on PIC cystograms Given these data, patients with the highest likelihood of spontaneous resolution are young male children, younger than the age of 2, with normal kidneys. Knudson M.J., Austin J.C., McMillan Z.M., et al: Predictive factors of early spontaneous resolution in children with primary vesicoureteral reflux. J Urol 178. 1684-1688.2007; Positioning the Instillation of Contrast at the ureteral orifice at the time of Cystoscopy VUR SASP 2006
Antenatally discovered VUR differs from VUR discovered in older symptomatic children, because in antenatal VUR:

A. grades I - IV show mid-kidney scars.
B. function of the refluxing kidney is diminished.
C. severe damage is mostly in males.
D. kidney damage is usually left sided.
E. resolution rates are slower. C. Severe damage is mostly in males.

Antenatally discovered VUR seems to be different from VUR discovered in a symptomatic older child. It is most commonly seen in males and is associated with high pressure voiding due to increased urethral resistance that resolves with time. Severe renal damage is more often seen in males with grade V VUR. The majority of kidneys with grades I - IV VUR show normal function and morphology. When renal damage occurs it is usually a global reduction of renal parenchyma. Resolution rates in antenatally discovered VUR are the same and possibly slightly better than that discovered in older symptomatic children. 2010 SASP: A healthy newborn boy has bilateral Grade 4 VUR. This is most commonly associated with:
A. low outlet resistance.
B. uninhibited detrusor contractions, coordinated voiding.
C. poor bladder compliance.
D. high pressure voiding with high residual.
E. lack of detrusor contractility. ANSWER=D. High pressure voiding with high residual.

Reflux in newborn boys is commonly high grade and associated with uninhibited detrusor contractions during filling, high pressure voiding due to elevated outlet resistence, detrusor­sphincter dyssynergy, and high postvoid residuals. Uninhibited detrusor contractions associated with coordinated voiding is normal in infants and not associated with high grade VUR. Compliance and contractility are generally within the range of normal for these boys. The best treatment for infant boys with high grade VUR is prophylactic antibiotics and observation. Most of these infants will decrease their outlet resistance and resolve their VUR with neurourologic maturation during the first year of life. A nine-year-old girl with a history of documented asymptomatic bacteruria changes pediatricians. The new physician treats her bacteruria with multiple courses of antibiotics. She then develops pyelonephritis twice in a six month period. Her VCUG, renal ultrasound, and toilet habits are normal. Her pyelonephritis is likely due to:

A. intermittent VUR.
B. change in bacterial strain.
C. menarche.
D. subclinical constipation.
E. detrusor sphincter dyssynergia. 2008 SASP: B

The most likely etiology of her new symptomatic UTI's is a change in the bacterial strain resident in her bladder. This is often due to misdirected efforts to eradicate her asymptomatic
bacteruria with antibiotics thus leading to a more virulent bacteria strain. The risk for development of pyelonephritis in a girl over four years of age with untreated asymptomatic
bacteruria is small and seems to be associated with a change in bacterial strain. A four-year-old girl with bilateral grade 3 VUR has two breakthrough UTls in six months. She has three to four episodes of urinary incontinence per day and two hard bowel movements per week. She is neurologically normal. A DMSA renal scan is normal. The next step is:
A. bilateral subureteric injection.
B. bilateral reimplantation.
C. oxybutynin and timed voiding.
D. treatment of constipation and bilateral subureteric injections.
E. treatment of constipation and timed voiding. 2010 SASP. ANSWER=E

The likely cause of this child's breakthrough infections is dysfunctional elimination syndrome, which may be present in as many as 20% or more of children with VUR. The enuresis and constipation are indicative of abnormal function. While she may ultimately need reimplantation, it is prudent to attempt to control her voiding dysfunction before undertaking surgical repair. Correction of VUR will not treat the underlying pathology. Her voiding dysfunction includes both bladder and bowel components and both need to be addressed with a timed voiding regimen and effective treatment of constipation. Oxybutynin will exacerbate the constipation and should be used only in refractory cases unresponsive to timed voiding and bowel management. A four-year-old girl undergoes a left cross trigonal ureteroneocystostomy with ureteral tapering for grade 5 VUR. A left renal ultrasound six weeks following surgery shows significant hydroureteronephrosis. The next steps are to continue prophylactic antibiotics and:

A. repeat ultrasound in four weeks.
B. MAG-3 renal scan.
C. percutaneous nephrostomy.
D. ureteral stent placement. There is considerable postoperative edema at the level of the bladder four to six weeks' following a tapered ureteroneocystostomy. In addition, high grade VUR results in diminished compliance of the ureter and renal pelvis. Prior to surgery, it is common to see a normal upper' tract on renal ultrasound or only minimal hydroureteronephrosis. After surgery the combination of the resistance from the ureteral tunnel and operative edema can unmask the poor compliance of the ureter and kidney resulting in the appearance of significant hydroureteronephrosis. This should not be interpreted as obstruction. When evaluating the immediate post operative ultrasound it is necessary to put it into perspective with the initial degree of ureteral and renal dilation noted on the VCUG and not directly compare it to the preoperative renal ultrasound. In general, there is no major concern for obstruction if the' degree of hydronephrosis on the post operative ultrasound correlates with the degree of; dilation of the collecting system seen on the preoperative VCUG. Increased dilation due to; edema and a poorly compliant system will begin to improve after six weeks. If this dilation persists after several months, a MAG 3 renal scan should be performed to aid in determining if post operative obstruction exists. All of the other options would be too premature at this point in time. R: In siblings of children with VUR, a voiding cystourethrogram or
radionuclide cystogram is recommended if there is evidence of renal cortical abnormalities or renal size asymmetry on ultrasound or if there is a history of urinary tract infection in the sibling who has not been tested. O: Given that the value of identifying and treating VUR is unproven, an observational approach without screening for VUR may be taken for siblings of children with VUR, with prompt treatment of any acute urinary tract infection and subsequent evaluation for VUR O: Sibling screening of older children who are toilet trained may be offered, although the value of identification of VUR is undefined. O: Ultrasound screening of the kidneys in the sibling of a child with VUR may be performed to identify significant renal scarring and to focus attention on the presence and potential further risk of VUR. O: Ultrasound screening of the kidneys in the sibling of a child with VUR may be performed to identify significant renal scarring and to focus attention on the presence and potential further risk of VUR. R: Voiding cystourethrogram is recommended for children with high-grade ((Society of Fetal Urology grade 3 and 4) hydronephrosis, hydroureter or an abnormal bladder on ultrasound (late-term prenatal or postnatal), or who
develop a urinary tract infection on observation. O: An observational approach without screening for VUR, with prompt treatment of any urinary tract infection, may be taken for children with prenatally detected hydronephrosis (Society of Fetal Urology grade 1 or 2), given the unproven value of identifying and treating VUR. It is also considered an option to perform a voiding cystourethrogram in these patients to screen for VUR R: Treat BBD before surgical intervention for VUR is undertaken.
R: CAP is recommended for the child with bladder/bowel dysfunction and VUR due to the increased risk of urinary tract infection while bladder/bowel dysfunction is present and being treated.

O: CAP may be considered for the child over one year of age with a history of urinary tract infections and VUR in the absence of bladder/bowel dysfunction

O: Observational management without continuous antibiotic prophylaxis, with prompt initiation of antibiotic therapy for urinary tract infections, may be considered for the child with VUR in the absence of bladder/bowel dysfunction, recurrent febrile urinary tract infections, or renal cortical abnormalities.
While this approach is currently under investigation and therefore no firm recommendation can be made, preliminary data suggest that some groups of patients with VUR may do as well with this approach as with continuous antibiotic prophylaxis.
O: Surgical intervention for VUR, including both open and endoscopic methods, may be used. Prospective randomized, controlled trials have shown a reduction in the occurrence of febrile urinary tract infections in patients who have undergone open surgical correction of VUR as compared to those receiving continuous antibiotic prophylaxis.

R: In the absence of a history of febrile urinary tract infections,
continuous antibiotic prophylaxis is recommended for the child less than one year of age with VUR grades III–V who is identified through screening. O: In the absence of a history of febrile urinary tract infections, the child less than one year of age with VUR grades I–II who is identified through screening may
be offered continuous antibiotic prophylaxis. O: Circumcision of the infant male with VUR may be considered based on an increased risk of urinary tract infections in boys who are not circumcised compared to those who are circumcised. Although there are insufficient data to evaluate the
degree of this increased risk and its duration, parents need to be made aware of this association to permit informed decision-making.
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