1. Angela Kosarek, PGY-3 August 19, 2010
Evidence Based Medicine: In young children with first UTI, is DMSA scan effective in diagnosing VUR?
Angela Kosarek, PGY-3
August 19, 2010

2. 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.

3. 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.

4. 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

5. 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

6. 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

7. 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

8. Primary vs. 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

9. 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 months to determine whether VUR has resolved

10. 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

11. 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

12. 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

13. 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

14. 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?

15. 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

16. 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

17. 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

18. 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:

19. 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

20. 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

21. 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%

22. 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

23. 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%)

24. 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 II 21 15 6
Low 24
15 (62.5%) 9
III 11 2 IV 20 V 12
High 43
41 (95.3%)
21 follow up
19 resolved or down-graded

25. 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
Follow-up not reported for 3 children

26. 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

27. 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
83.6
Specificity
71.2
76.5
56.9
Positive Predictive Value
51.6
56.6
45.9
Negative Predictive Value
84.5
85.4
88.8

28. 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

29. 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

30. 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

31. Comparison of Parameters of US and DMSA scan for Detection of VUR
Article 1 (grades I-V)
Article 2 (grades III-V)
Sensitivity
83.6
73.9
Specificity
56.9
56.0
Positive Predictive Value
45.9
23.6
Negative Predictive Value
88.8
92.1

32. 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):
Hoberman A et al: Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics 1999; 104(1):