Evidence Based Medicine:
In young children with first UTI, is DMSA scan
effective in diagnosing VUR?
Angela Kosarek, PGY-3
August 19, 2010
Our patient
• Patient is a 17 month old male with Trisomy 21
admitted for repair of an unbalanced AV canal.
• One week prior to admission at Children’s
Hospital, he presented to an outside hospital
with c/o fever.
• Urine culture (from transurethral
catheterization) was positive for >100,000
cfu/ml of E. coli.
Our patient
• He completed a 14 day course of antibiotics
based on bacterial antibiogram.
• Renal ultrasound was normal.
• Patient’s mother refused further evaluation for
VUR with VCUG due to the invasive nature and
anticipated discomfort of the procedure.
Recommended Imaging Studies for
Culture-Positive UTI
• Renal ultrasound & voiding cystourethrogram
▫ Indicated for all male patients with their 1st UTI,
all female patients < 5 years of age, and all
children with recurrent UTI
• Renal ultrasound
▫ Noninvasive, nonionizing evaluation for gross
structural defects, obstructive lesions, positional
abnormalities, and renal size and growth
Recommended Imaging Studies for
Culture-Positive UTI
• Voiding Cystourethrogram (VCUG)
▫ Obtained by the use of fluoroscopy and a contrast
agent introduced through a catheter in the bladder
▫ Performed when asymptomatic and cleared of
bacteriuria
▫ Visualizes bladder and urethral anatomy
▫ Diagnostic of vesicoureteral reflux (VUR) upon
the demonstration of urine refluxing from the
bladder to the upper urinary tract
Grading Classification of VUR
• I: reflux only fills ureter without dilation
• II: reflux fills ureter & collecting system without dilation
• III: filling and mild dilation of ureter & collecting system with mild blunting
of calyces
• IV: filling & gross dilation of ureter & collecting system with blunting of
calyces; some ureteral tortuosity
• V: gross dilation of collecting system; calyceal blunting with loss of papillary
impression; significant ureteral dilation & tortuosity
Primary vs. Secondary VUR
• Primary VUR
▫ Most common form
▫ Normally reflux is prevented during bladder
contraction by fully compressing the
intravesicular ureter and sealing it off with the
surrounding bladder muscles
▫ Results from incompetent or inadequate closure of
the ureterovesical junction (UVJ)
▫ Spontaneous resolution can occur with growth
Primary vs. Secondary VUR
• Secondary VUR
▫ Abnormally high pressure in the bladder causes
failure of closure of the UVJ during bladder
contraction
▫ Often associated with anatomic (e.g., posterior
urethral valves) or functional bladder obstruction
(e.g., dysfunctional voiding & neurogenic bladder)
▫ Management: initial treatment of the associated
abnormality followed by surgical correction of the
VUR, if necessary
Nonsurgical management of VUR
• Antimicrobial prophylaxis
▫ Amoxicillin in first 2 months of life
▫ Otherwise trimethoprim-sulfamethoxazole or
nitrofurantoin
• UTI Surveillance
▫ Urine cultures every 4 months and when febrile
▫ Change antibiotic therapy if breakthrough UTI
• VUR follow-up
▫ Repeat VCUG in 12-18 months to determine
whether VUR has resolved
Indications for Surgical Management
• Grade V reflux with scarring in children > 1 year
of age
• Grade V reflux in children > 6 years of age
• Grade IV reflux with either bilateral reflux or
renal scarring in children > 6 years of age
• Children with breakthrough pyelonephritis while
on prophylaxis
Why do we care about VUR?
• Current management is based upon premise that
VUR predisposes to acute pyelonephritis
▫ VUR allows transportation of bacteria from the
bladder to the kidney
▫ Resulting infection may lead to renal scarring, the
loss of renal parenchyma between the calyces and
the renal capsule
▫ Effects of extensive scarring include HTN,
decreased renal function, proteinuria, and
sometimes ESRD
Should we care about VUR?
• Alternate viewpoint of primary VUR:
▫ Does not play a causative role in chronic kidney
disease (CKD)
▫ Serves as marker for abnormal renal development
▫ Disruption in renal development leads to
decreased formation of normal parenchyma,
resulting in increased risk of poor renal outcome
• Limited data comparing the effect of VUR
treatment versus no treatment (i.e.,
surveillance) upon CKD and renal scarring
RIVUR Study
• Randomized Intervention for Children with
Vesicoureteral Reflux Study
▫ 2 year multicenter, double-blind, randomized,
placebo-controlled trial
▫ Objective: to determine if prophylaxis with
trimethoprim-sulfamethoxazole prevents
recurrent UTI and renal scarring with VUR
Clinical Question
• In young children after a first febrile urinary
tract infection, is a dimercaptosuccinic acid
(DMSA) scan, in combination with renal
ultrasound, as sensitive and specific in
diagnosing VUR as a VCUG?
DMSA scan
• Evaluates the size, shape, and position of the
kidneys
▫ Does not visualize urethral anatomy
• Detects areas of decreased uptake that may
represent acute pyelonephritis or renal scarring
• Limitations
▫ Not sensitive for low-grade reflux
▫ Cannot grade reflux
DMSA scan
• Requires injection of a radioisotope (tracer)
through an IV catheter
• 2-4 hour lag time between injection of tracer and
imaging
• Study does not permit any movement and may
take up to 1 hour to perform
• 1/100 the radiation exposure of VCUG
DMSA scan
• normal: homogenous uptake of the radioisotope
throughout the kidneys with preservation of the renal
contour
• with acute pyelonephritis or renal scarring: focal or
diffuse areas of decreased uptake
The efficacy of ultrasound and
dimercaptosuccinic acid scan in
predicting vesicoureteral reflux in
children below the age of 2 years with
their first febrile urinary tract infection
Hye-young Lee, Byung Hyun Soh, Chang Hee
Hong, Myung Joon Kim, Sang Won Han
Pediatric Nephrology (2009) 24:2009-2013
Patients and Methods
• Retrospective analysis
▫ Medical records and radiological imaging studies
• Children younger than 2 years diagnosed with 1st
febrile UTI from January 2001 to May 2007
▫ Febrile UTI: temp > 38.5° C with significant
bacteriuria ( > 105 cfu/ml)
▫ Urine samples: Midstream clean catch in boys &
transurethral catheter in girls
Patients and Methods
• All patients underwent renal US, DMSA scan, &
VCUG
▫ US performed immediately after diagnosis
▫ DMSA & VCUG performed after resolution of
fever & confirmation of a negative urine culture
• Excluded patients
▫ Neurological abnormalities that might have effect
on voiding function
▫ Obstructive diseases of the urinary tract
▫ History of previous UTI
Patients and Methods
• Abnormal findings suggestive of VUR:
▫ US:





Dilatation of renal pelvis or ureter
Increase of renal echogenicity
Reduction in thickness of renal parenchyma
Irregularity of kidney margin
Loss of corticomedullary differentiation
▫ DMSA scan:
 More than one cortical photon defect
 Reduction in uptake of radioisotope
 Split renal function lower than 45%
Patients and Methods
• VUR was graded in accordance with grading
system as defined by International Reflux Study
Committee
▫ Grades I-II: classified as low grade reflux
▫ Grades III-V: classified as high grade reflux
• Prophylactic antibiotics
▫ Low grade reflux with persistent pyuria
▫ High grade reflux
• Patients followed for mean of 23.2 months
Results
• Among 220 children diagnosed with UTI:
▫
▫
▫
▫
162 (73%) boys & 58 (27%) girls
212 (96.4%) younger than 1 year
Mean age 4.5 months (range 0.1 – 21 months)
67 children (30.4%) diagnosed with VUR by
VCUG
 Low grade: 24 cases (35.8%)
 High grade: 43 cases (64.2%)
Findings suggestive of VUR on US and
DMSA scan according to grade of VUR
VUR grade
Total
+ Findings on
US or DMSA
- Findings on
US and DMSA
I
3
0
3
II
21
15
6
Low
24 21 follow up
15 (62.5%)
9
III
11
9
2
IV
20
20
0
V
12
12
0
High
43
41 (95.3%)
2
19 resolved or down-graded
Follow-up for low grade VUR
• 24 children:
▫ 8 with negative US & DMSA scan
 Spontaneous resolution or down-grading of VUR
 No complications related to VUR
▫ 13 with positive US or DMSA scan
 12 had spontaneous resolution or down-grading of
VUR
 1 showed no change
 No complications related to VUR
▫ Follow-up not reported for 3 children
Follow-up for high grade VUR
• Grade III detected on US or DMSA scan
▫ 1 patient down-graded to grade II VUR
▫ Remaining 8 children underwent anti-reflux
surgery
(Follow-up not reported for the 2 undetected cases)
• Grade IV
▫ 2 patients down-graded to low grade VUR
▫ 2 patients with resolution of VUR
▫ Remaining 16 underwent anti-reflux surgery
• Grade V
▫ All 12 underwent surgical correction
Sensitivity, specificity, and positive
and negative predictive values of US,
DMSA, and US with DMSA for detection
of VUR
Parameter
US (%)
DMSA (%)
US and DMSA
(%)
Sensitivity
70.1
70.1
83.6
Specificity
71.2
76.5
56.9
Positive Predictive 51.6
Value
56.6
45.9
Negative
Predictive Value
85.4
88.8
84.5
Discussion
• Retrospective evaluation
▫ The preferred study to evaluate efficacy of a
diagnostic test: a prospective, blind comparison
to a gold standard study
▫ Efficacy of US and DMSA scan were evaluated
only in VUR-positive individuals
Discussion
• In this study, 95.3% (41/43) of high grade VUR
could be predicted by US and DMSA scan
▫ 2 patients in whom VUR could not be detected
had Grade III VUR and showed spontaneous
improvement
• Limited in detection of low grade reflux (62%)
▫ Spontaneous resolution or down-grading of VUR
in 19/21 children during follow-up
▫ No complications related to VUR
DMSA Scan for Revealing
Vesicoureteral Reflux in Young
Children With Urinary Tract Infection
Sotirios Fouzas, Erifyli Krikelli, Pavlos Vassilakos,
Despoina Gkentzi, Dimitrios A. Papanastasiou
and Christos Salakos
Pediatrics published online Aug 2, 2010
Comparison of Parameters of US and
DMSA scan for Detection of VUR
Parameter
Article 1 (grades I-V)
Article 2 (grades IIIV)
Sensitivity
83.6
73.9
Specificity
56.9
56.0
Positive Predictive Value
45.9
23.6
Negative Predictive
Value
88.8
92.1
References
•
•
•
•
www.uptodate.com
www.hsl.unc.edu
www.chop.edu
Keren R et al: Rationale and Design Issues of the Randomized
Intervention for Children with Vesicoureteral Reflux (RIVUR)
Study. Pedatrics 2008; 122(Suppl 5): S240-S250.
• American Academy of Pediatrics, Committee on Quality
Improvement, Subcommittee on Urinary Tract Infection:
Practice parameter: The diagnosis, treatment, and evaluation
of initial urinary tract infection in febrile infants and young
children. Pediatrics 1999; 103(4): 843-852.
• Hoberman A et al: Oral versus initial intravenous therapy for
urinary tract infections in young febrile children. Pediatrics
1999; 104(1): 79-86.