1. Deflux® clinical update
April 17, 2017
Deflux® clinical update

2. List of key references (1)
April 17, 2017
List of key references (1)
Safety
Stenberg et al. Injectable dextranomer-based implant: histopathology, volume changes and DNA-analysis. Scand J Urol Nephrol 1999; 33: 355–61
Stenberg et al. Endoscopic treatment with dextranomer-hyaluronic acid for vesicoureteral reflux: histological findings. J Urol 2003; 169: 1109–13
Stenberg et al. Lack of distant migration after injection of a 125iodine labelled dextranomer based implant into rabbit bladder. J Urol 1997; 158: 1937–41
Efficacy
Kirsch et al. The modified STING procedure to correct vesicoureteral reflux: improved results with submucosal implantation within the intramural ureter. J Urol 2004; 171: 2413–6
Yu and Roth. Treatment of vesicoureteral reflux using endoscopic injection of nonanimal stabilized hyaluronic acid/dextranomer gel: initial experience in pediatric patients by a single surgeon. Pediatrics 2006; 118: 698–703
Efficacy: long term
Läckgren et al. Long-term followup of children treated with dextranomer/hyaluronic acid copolymer for vesicoureteral reflux. J Urol 2001; 166: 1887–92
Stenberg and Läckgren. Treatment of vesicoureteral reflux in children using stabilized non-animal hyaluronic acid/dextranomer gel (NASH/Dx): a long-term observational study. J Pediatr Urol 2007; 3: 80–85
This slide kit is designed to summarise key clinical data relating to the use of Deflux for vesicoureteral reflux (VUR) in children.
This slide shows a list of articles included in the slide kit.
Supporting notes
Use the arrow buttons to hyperlink directly to the slides relating to that reference.
Use the ‘home’ button on the conclusions slides to hyperlink back to the list of key references.

3. List of key references (2)
April 17, 2017
List of key references (2)
Antibiotics vs endoscopic injection
Capozza and Caione. Dextranomer/hyaluronic acid copolymer implantation for vesico-ureteral reflux: a randomized comparison with antibiotic prophylaxis. J Pediatr 2002; 140(2): 230–4
Koyle et al. Critical appraisal: antibiotic prophylaxis and endoscopic injection for VUR. Issues in Urology 2006; 18(3): 123–30
Complicated cases
Läckgren et al. Endoscopic treatment of vesicoureteral reflux with dextranomer/hyaluronic acid copolymer is effective in either double ureters or a small kidney. J Urol 2003; 170: 1551–5
Perez-Brayfield et al. Endoscopic treatment with dextranomer/hyaluronic acid for complex cases of vesicoureteral reflux. J Urol 2004; 172: 1614–6.
Läckgren et al. Endoscopic treatment with stabilized nonanimal hyaluronic acid/dextranomer gel is effective in vesicoureteral reflux associated with bladder dysfunction. J Urol 2007; 177:1124–8.
Parental preference
Capozza et al. Treatment of vesico-ureteral reflux: a new algorithm based on parental preference. BJU Int 2003; 92: 285–8
Resolution
Schwab et al. Spontaneous resolution of vesicoureteral reflux: a 15 year perspective. J Urol 2002; 168: 2594–9
This slide shows a list of articles included in the slide kit.

4. April 17, 2017
Safety

5. Stenberg et al. 1999, histopathology, volume, DNA – introduction
April 17, 2017
Stenberg et al. 1999, histopathology, volume, DNA – introduction
Article type
Original research – Deflux safety study
Objective
Monitor any changes in the tissues (histopathology), implant volume and DNA profile of invading cells after Deflux injection into pigs and rats
Methods
Preclinical (animal)
Pigs: n=9, follow-up 2 weeks to 3.5 months; rats: n=34, follow-up 3 weeks to 16 months
Deflux injection into the bladder (pigs) or subcutaneous tissue (rats)
Histopathological analysis: 16 pig, 63 rat implants
DNA profile: 31 rat implants
Changes in implant volume over time: 51 rat implants analysed for up to 12 months after implantation
Full citation
Stenberg ÅM, Larsson E, Lindholm A, Ronneus B, Stenberg A, Läckgren G. Injectable dextranomer-based implant: histopathology, volume changes and DNA-analysis. Scand J Urol Nephrol 1999; 33: 355–61.
Article type
Original research – this is an original research manuscript reporting a preclinical Deflux histolopathology, volume change and DNA analysis.
Objective
To monitor the tissue reaction in and around the Deflux implant after injections into pig bladder and subcutaneous tissue in rats, measure changes in implant volume over time and study the DNA profile of cells in and around the implants.
Methods
The study included 9 pigs (follow-up 2 weeks to 3.5 months) and 34 rats (follow-up 3 weeks to 16 months).
Pigs received Deflux injections into the bladder and rats into subcutaneous tissue.
Tissue analysis (histopathology) was performed in 16 pigs and 63 rat implants.
DNA profile was analysed in 31 rat implants.
Changes in implant volume over time were estimated in 51 rat implants over 12 months post-implantation.

6. Stenberg et al. 1999, histopathology, volume, DNA – results
April 17, 2017
Stenberg et al. 1999, histopathology, volume, DNA – results
Histopathology
A mild inflammatory response of the foreign body type (identification of giant cells, macrophages and lymphocytes) was observed
No cell death was identified in the tissues surrounding the implant
Volume change
Implant volume decreased by 23% at 12 months post-injection
DNA profile
No changes in the cells that would indicate tumour formation were seen and no change in the DNA profile was observed
Immune cells that indicate a mild, foreign body type inflammatory reaction (macrophages, lymphocytes and giant cells) were seen.
There was no evidence of cell death (tissue necrosis) around the implant.
Implant volume decreased by 23% over the 12 months post-injection; the Deflux implant remained in situ during this period.
There was no change in the DNA pattern during the study period in either species.
No pathological changes such as tumour formation or enlarged lymph nodes were observed in either the pigs or rats at autopsy.

7. Stenberg et al. 1999, histopathology, volume, DNA – conclusions
April 17, 2017
Stenberg et al. 1999, histopathology, volume, DNA – conclusions
Deflux does not induce any major tissue changes in and around the implant
Deflux treatment is associated with a foreign body reaction, as expected
The volume of the implant remained stable over 12 months
Deflux is not associated with any signs of malignant transformation (risk of cancer) or tissue necrosis
This study demonstrates that Deflux does not induce any major tissue changes in and around the implant.
There is good tolerance in response to implantation in experimental animals, with an expected foreign body reaction at the injection site.
The implant underwent a slight decrease in volume over 12 months (23%), indicating that it remains stable over time.
Investigations under the microscope, together with DNA measurements over the 16-month study revealed no signs of an increased risk of cancer or tissue necrosis.
“After injection of DiHA [Deflux] into the experimental animals no unexpected adverse events were noted and no safety concerns were raised”

8. Stenberg et al. 2003, histological findings – introduction
April 17, 2017
Stenberg et al. 2003, histological findings – introduction
Article type
Original research – Deflux histological study
Objective
Evaluate any changes in the tissues (histology) associated with Deflux injection in children with VUR
Methods
Retrospective
Children (n=13) aged 0–7 years at diagnosis of VUR
Persistent reflux grades III–V following treatment with Deflux
Deflux implant and surrounding tissue removed during surgical treatment (ureteral reimplantation) for VUR and fixed for analysis
Patients (n=10) with similar grade VUR, but no previous endoscopic treatment included as controls
Full citation
Stenberg A, Larsson E, Läckgren G. Endoscopic treatment with dextranomer-hyaluronic acid for vesicoureteral reflux: histological findings. J Urol 2003; 169: 1109–13.
Article type
Original research – this is an original research manuscript reporting a Deflux histological study.
Objective
To evaluate any changes in the tissues (histology) surrounding the implant following injection of Deflux in children with VUR.
Methods
Retrospective analysis.
A total of 13 children received 1–3 Deflux treatments using the subureteric transurethral injection (STING) technique.
The children:
were aged between 0 and 7 years at the time of VUR diagnosis
had persistent reflux grade III to V following Deflux treatment
were referred for open surgery (ureteral reimplantation).
At ureteral reimplantation, the implant and surrounding ureteral tissue was removed and prepared for histopathological analysis under the light microscope.
Patients (n=10) with a similar reflux grade, but no previous endoscopic treatment, were included as controls.
VUR, vesicoureteral reflux

9. Stenberg et al. 2003, histological findings – results
April 17, 2017
Stenberg et al. 2003, histological findings – results
Location of implant
The implant remained in situ for 13–39 months (mean 22 months)
The implant was located at the site of injection in 12/13 patients (92%)
Distal ureter
A mild inflammatory reaction (presence of multinucleated giant cells) was observed at the implantation site
the degree of fibrosis and mast cell infiltration was similar in treatment and control groups
Implantation site
Implant pseudo-encapsulation (development of a capsule of fibrous material surrounding the implant) and calcification was present in 9 implants
The Deflux implant remained in situ for 13–39 months (mean 22 months) and was located at the site of the injection in 92% of patients (12/13).
A mild granulomatous inflammatory reaction was indicated by giant cell infiltration and other inflammatory cells (e.g. lymphocytes and plasma cells).
Fibrosis and mast cell infiltration were observed in all cases, with no differences between the treatment and control groups.
A fibrotic pseudocapsule was observed surrounding 9 implants, with calcification also evident in 9 ureters.

10. Stenberg et al. 2003, histological findings – conclusions
April 17, 2017
Stenberg et al. 2003, histological findings – conclusions
A long duration of implant persistence after Deflux treatment is consistent with the clinical findings (long-term resolution of reflux)
As expected, Deflux treatment is associated with a mild inflammatory reaction at the implantation site
The histological findings are typical following implantation of a foreign material
The long duration of implant persistence revealed in this study is consistent with the clinical findings with Deflux (i.e. long-term resolution of reflux in children with VUR).
Deflux treatment is associated with a granulomatous inflammatory reaction at the implantation site, which is as expected.
Inflammatory reactions are typical following implantation of a foreign material and have also been observed with other bulking agents (e.g. polytetrafluoroethylene; PTFE).
The degree of fibrosis and mast cells was similar in the treated and control groups suggesting that these responses are a feature of VUR, rather than due to the implant.
“Dextranomer-hyaluronic acid co-polymer was well tolerated and remains a safe and effective bulking agent for vesicoureteral reflux”

11. Stenberg et al. 1997, lack of migration – introduction
April 17, 2017
Stenberg et al. 1997, lack of migration – introduction
Article type
Original research – Deflux safety study
Objective
Investigate any possible migration of dextranomer particles after implantation of a radioactive Deflux implant
Methods
Preclinical (animal)
125Iodine-labelled dextranomer particles were mixed with a nonradioactive Deflux solution
Labelled detranomer microspheres injected into rabbit bladder wall (n=6)
Samples of blood and various tissues were examined for radioactivity over 28 days
The whole body was examined on day 1 and weeks 1 and 4 post-injection
Full citation
Stenberg ÅM, Sundin A, Larsson BS, Läckgren G, Stenberg A. Lack of distant migration after injection of a 125iodine labelled dextranomer based implant into the rabbit bladder. J Urol 1997; 158: 1937–41.
Article type
Original research – this is an original research manuscript reporting a Deflux preclinical study.
Objective
To investigate any possible migration of detranomer particles after implantation of a radioactively labelled Deflux implant into rabbits.
Methods
Dextranomer microspheres were radiolabelled with 125iodine and mixed with a nonradioactive Deflux solution.
Labelled detranomer microspheres were injected the submucosal space of rabbit bladders (n=6).
Samples of blood and various tissues were examined for radioactivity at scheduled intervals over 28 days.
Whole body autoradiography was performed on day 1 and weeks 1 and 4 post-injection.

12. Stenberg et al. 1997, lack of migration – results
April 17, 2017
Stenberg et al. 1997, lack of migration – results
Injection of radioactively labelled dextranomer into the bladder wall
Leakage in urine
Bladder wall – 45% remaining
Blood, brain, spleen, lung, liver – background levels
In the bladder, 45% of the radioactivity remained in the wall after 28 days.
Radioactivity in the blood was low at all timepoints investigated (<11% above background).
Other organs had levels only 0% to 8% above background.
Radioactivity in the tissues also remained at background levels in all samples except the thyroid where uptake of free 125iodine was detected.
It is likely that the remainder of the dose disappeared from the bladder wall by leakage into the urine shortly after deposition.

13. Stenberg et al. 1997, lack of migration – conclusions
April 17, 2017
Stenberg et al. 1997, lack of migration – conclusions
Almost half of the injected dose of radioactivity remained in the bladder wall after 28 days
Levels of radioactivity in the blood and other organs were very low
These findings confirm the lack of migration of dextranomer particles from the injection site
“Judging by the findings of only background levels of radioactivity in organs and the circulation, there was no migration of particles from the implant in our study”
Almost half (45%) of the injected dose of radioactivity remained in the bladder wall after 28 days.
Levels of radioactivity were very low in the blood and other organs.
These findings confirm the lack of migration of dextranomer particles from the injection site.

14. April 17, 2017
Efficacy

15. Kirsch et al. 2004, modified STING procedure – introduction
April 17, 2017
Kirsch et al. 2004, modified STING procedure – introduction
Article type
Original research – Deflux clinical study
Objective
Assess the efficacy of Deflux injection using two implantation techniques: STING and HIT
Methods
Prospective comparison of surgical methods
STING, n=52 patients; HIT, n=70
Children aged 7 months to 15 years
Reflux grades II–IV (and grade I contralateral reflux)
One treatment with Deflux
Follow-up VCUG at 3 months post-treatment
Full citation
Kirsch AJ, Perez-Brayfield M, Smith EA, Scherz HC. The modified STING procedure to correct vesicoureteral reflux: improved results with submucosal implantation within the intramural ureter. J Urol 2004; 171: 2413–6.
Article type
Original research – this is an original research manuscript reporting a Deflux clinical study.
Objective
To assess the efficacy of Deflux injection for VUR using two implantation techniques: the procedure currently used as standard, STING, and a modified technique known as the hydrodistention implantation technique (HIT).
Methods
A prospective comparison of surgical techniques for endoscopic treatment of VUR.
A total of 52 children were treated using the STING technique, and 70 using the HIT.
The children:
were aged between 7 months and 15 years
had reflux grade II to IV in one or both ureters before treatment. If grade I reflux was identified in the second ureter (i.e contralateral reflux), this was also treated
received a single Deflux treatment (i.e. one injection) between October 2001 and October 2003
were followed for up to 24 months: VUR status was investigated by voiding cystourethrogram (VCUG) 3 months post-treatment.
Supporting notes
The HIT is based on the standard STING procedure, but with the following adaptations:
a pressurised stream of irrigation fluid is directed into the ureter to aid visualisation of the ureteral tunnel
the implant is positioned within the submucosa of the ureter to increase closing or coaptation of the ureteral tunnel (STING involves injection just below the ureter).
STING, subureteric transurethral injection; HIT, hydrodistention implantation technique; VCUG, voiding cystourethrogram

16. Kirsch et al. 2004, modified STING procedure – results
April 17, 2017
Kirsch et al. 2004, modified STING procedure – results
p<0.05
Cure rate (patients, %)
Overall, 76% of children were cured of reflux (defined as reflux grade 0 following treatment) with a single Deflux injection.
The cure rate was significantly higher with the HIT compared with the standard STING procedure (89% vs 71%, p<0.05).
Both implantation techniques were well tolerated: there were no cases of hydronephrosis (collection of urine in one or both of the kidneys leading to swelling) up to 24 months’ follow-up.
No significant short-term complications were introduced by using the HIT technique.
STING, subureteric transurethral injection; HIT, hydrodistention implantation technique

17. Kirsch et al. 2004, modified STING procedure – conclusions
April 17, 2017
Kirsch et al. 2004, modified STING procedure – conclusions
The majority of children can expect to be cured following a single injection of Deflux
Improvements in cure rate can be achieved using a modified implantation technique, the HIT
Both implantation techniques are well tolerated (no significant short-term adverse events)
“The modified STING [HIT] is our preferred method of implant injection for the correction of VUR and in our hands produces a resolution rate of 89%”
This study demonstrates that, regardless of the technique used, most children will be cured of VUR following a single Deflux treatment (overall cure rate of 76%).
Introduction of the HIT has further improved success rates with Deflux injection.
The HIT does not appear to raise the risk of complications associated with treatment. Increased experience with the HIT will help identify any further benefits or risks associated with this adapted procedure.
STING, subureteric transurethral injection; HIT, hydrodistention implantation technique; VUR, vesicoureteral reflux

18. Yu and Roth 2006, experience by a single surgeon – introduction
April 17, 2017
Yu and Roth 2006, experience by a single surgeon – introduction
Article type
Original research – Deflux clinical study
Objective
Assess the efficacy and safety of Deflux injection during the centre’s first 18 months of using the treatment
Methods
Open, prospective
Children (n=107) aged 6 months to 15 years
Primary reflux grades I–V (unilateral or bilateral)
One or two treatments with Deflux; STING or HIT injection
Follow-up VCUG ≥2 weeks post-treatment
Full citation
Yu R and Roth D. Treatment of vesicoureteral reflux using endoscopic injection of nonanimal stabilized hyaluronic acid/dextranomer gel: initial experience in pediatric patients by a single surgeon. Pediatrics 2006; 118: 698–703.
Article type
Original research – this is an original research manuscript reporting a Deflux clinical study.
Objective
To assess the efficacy and safety outcomes for all patients treated with Deflux during the centre’s first 18 months of administering the treatment.
Methods
Open, prospective design.
A total of 107 children received Deflux, administered with either the subureteric transurethral injection (STING) procedure or the hydrodistention-implantation technique (HIT).
The children:
were aged between 6 months and 15 years
had primary reflux grade I to V (unilateral or bilateral). VUR was diagnosed by VCUG
received one or two Deflux treatments between June 2003 and January 2005
returned for a VCUG assessment ≥2 weeks post-treatment.
Resolution of reflux was defined as grade 0.
STING, subureteric transurethral injection; HIT, hydrodistention implantation technique; VCUG, voiding cystourethrogram

19. Yu and Roth 2006, experience by a single surgeon – results
April 17, 2017
Yu and Roth 2006, experience by a single surgeon – results
No. of Deflux injections
Resolution rate
First injection
Patients (n=107)
82.2%
Ureters (n=162)
86.9%
Second injection
Patients (n=14)
64.3%
Ureters (n=20)
Overall (1–2 injections)
90.7%
92.6%
VUR was resolved in 82.2% of children and 86.9% of ureters after a single Deflux injection.
The overall resolution rate increased to 90.7% after a second injection (required in 14 patients).
For the first 50 patients treated, resolution rate was 85.0%, which changed little for the second 50 patients (83.9%).
Deflux was well tolerated with mild and transient flank pain being the only adverse event (reported in two patients).

20. Yu and Roth 2006, experience by a single surgeon – conclusions
April 17, 2017
Yu and Roth 2006, experience by a single surgeon – conclusions
Deflux treatment can be successfully administered to children with VUR by a surgeon without previous experience of the technique
VUR can be cured using Deflux in the majority of children
Repeat injection of Deflux is viable and effective
“Endoscopic treatment with NASHA/Dx gel [Deflux]… should be considered as a first-line treatment in place of antibiotic prophylaxis”
This study demonstrates that Deflux treatment can be administered successfully to children with VUR, even if the physician has no previous experience of the technique.
The findings show that Deflux can cure VUR in a high proportion of patients, even those with high-grade reflux.
Repeat treatment with Deflux proved viable in the study, with reflux being resolved in >90% of patients and ureters after one or two treatments. Indeed, no children underwent open surgery during the study period.
Deflux should be considered an appropriate first-line treatment option for the majority of children with persistent VUR.
VUR, vesicoureteral reflux

21. April 17, 2017
Efficacy: long term

22. Läckgren et al. 2001, long-term follow-up – introduction
April 17, 2017
Läckgren et al. 2001, long-term follow-up – introduction
Article type
Original research – Deflux clinical study
Objective
Assess the long-term efficacy and safety of Deflux treatment in children with VUR
Methods
Open, prospective
Children (n=221) aged 1–15 years
Reflux grades III–V (unilateral or bilateral)
1–3 Deflux treatments; STING injection
Follow-up VCUG at 3 months and 1 year post-treatment
Mean follow-up 5 years; range, 2.0–7.5 years
Late VCUG at 2–5 years in select patients (n=49)
Full citation
Läckren G, Wåhlin N, Sköldenberg E, Stenberg A. Long-term followup of children treated with dextranomer/hyaluronic acid copolymer for vesicoureteral reflux. J Urol 2001; 166: 1887–92.
Article type
Original research – this is an original research manuscript reporting a long-term Deflux clinical study.
Objective
To assess the long-term efficacy and safety of Deflux treatment in children with VUR.
Methods
Open, prospective design.
A total of 221 children received Deflux injection using the STING technique.
The children:
were aged between 1 and 15 years
had reflux grade III to V in one or both ureters before treatment
received a follow-up VCUG at 3 months and 1 year post-injection.
Children with reflux grade ≥III at 3 months were offered retreatment; 1–3 treatments were performed.
Patients were followed for 2.0–7.5 years (mean 5 years).
STING, subureteric transurethral injection; VCUG, voiding cystourethrogram; VUR, vesicoureteral reflux

23. Läckgren et al. 2001, long-term follow-up – results
April 17, 2017
Läckgren et al. 2001, long-term follow-up – results
Baseline reflux grade
Ureteral response (%) 10 20 30 40 50 60 70 80 90
100
III (n=208)
IV (n=80)
V (n=6)
Cured
Improved
Unchanged
96% of ureters free from reflux at 3–12 months remained free from dilating reflux (grade ≥III) at 2–5 years.
At their last VCUG, 68% of patients showed a positive response (grade 0 or I) and 81% had no dilating reflux.
favourable results were seen for all grades of reflux.
When outcomes were examined for ureters, 77% of those with grade III reflux at baseline had a positive response at the last VCUG, and 66% of those with grade IV or V reflux.
Good response rates were observed with the second (43%) and third (50%) implantations compared with the first procedure (54%).
Very little deterioration was observed after the initial response to Deflux:
96% of ureters without reflux at 3–12 months post-treatment remained free from dilating reflux (grade III or above) at 2–5 years.
Of the 221 children who received Deflux treatment during the study, only 27 (12%) were referred for open surgery.

24. Läckgren et al. 2001, long-term follow-up – conclusions
April 17, 2017
Läckgren et al. 2001, long-term follow-up – conclusions
The response to Deflux treatment is sustained long-term
Many children only require a single Deflux treatment, though retreatment is a viable option
Deflux is well tolerated and there are no long-term safety concerns
“We would recommend endoscopic therapy with dextranomer/hyaluronic acid copolymer [Deflux] as first-line treatment for children with long-term VUR”
Patients responding to treatment had no sign of deterioration on a VCUG 2–5 years after treatment, demonstrating a sustained response.
Repeat injections of Deflux are viable in patients not responding to an initial treatment.
There are no long-term safety concerns with Deflux and the potential for immediate cure offered by the treatment offers several advantages over prophylactic antibiotics. For example, the continued therapy necessitated by the latter treatment may encourage emergence of bacterial resistance, breakthrough infection and poor compliance.
The findings of the study suggest that Deflux treatment should be recommended as first-line treatment for children with VUR.
VUR, vesicoureteral reflux

25. Stenberg and Läckgren 2007, observational study – introduction
April 17, 2017
Stenberg and Läckgren 2007, observational study – introduction
Article type
Original research – a long-term observational study of Deflux treatment
Objective
Investigate long-term outcomes and experiences of Deflux
Methods
Retrospective
Questionnaire sent to children (n=231) 7–12 years following Deflux treatment
Questionnaire assessed clinical outcome and patient/parental attitudes to treatment
Children aged 6 months to 23 years at the time of treatment
Reflux grades III–V before treatment, 0–II after treatment
Endoscopic injection; one (72%), two (20%) or three (4%) Deflux treatments
Full citation
Stenberg A and Läckren G. Treatment of vesicoureteral reflux in children using stabilized non-animal hyaluronic acid/dextranomer gel (NASH/Dx): a long-term observational study. J Pediatr Urol 2007; 3: 80–5.
Article type
Original research – this is an original research manuscript reporting a long-term Deflux observational study.
Objective
To investigate long-term outcomes and experiences of Deflux treatment.
Methods
Retrospective design.
A questionnaire was sent in 2005 to 231 children who received Deflux treatment between 1993 and 1998 (i.e. the questionnaire was sent 7 to 12 years after Deflux treatment).
The questionnaire assessed clinical outcome (incidence of urinary tract infections [UTIs]) and patient and parental attitudes to Deflux treatment).
The children:
were aged between 6 months and 23 years at the time of treatment
had reflux grade III to V before and grade 0 to II after treatment
received one (72%), two (20%) or three (4%) Deflux treatments.

26. Stenberg and Läckgren 2007, observational study – results
April 17, 2017
Stenberg and Läckgren 2007, observational study – results
Response rate
Questionnaire returned by 179 patients (77.5%)
UTIs post-treatment
UTI without fever: 21.8% (n=39)
UTI with fever: 3.4% (n=6)
Worst aspect of VUR treatment
Deflux treatment: patients, 9%; parents, 19%
Medication: patients, 19%; parents, 24%
VCUG: patients, 72%; parents, 57%
The questionnaire was returned by 179 patients, a response rate of 77.5%
A total of 45 patients (25.1%) experienced a UTI post-treatment, of which febrile UTI was confirmed in six cases (3.4%).
Of the patients who remembered how they felt about Deflux treatment (n=49):
discomfort and fear was reported by 47% and 39%, respectively
93.9% felt somewhat or very safe during the procedure.
When asked about the worst aspect of VUR treatment:
patients considered Deflux treatment to be the least bothersome aspect (9%), followed by receiving medication (19%), with VCUG viewed as the worst aspect (72%)
parents also rated VCUG as the worst aspect (57%), followed by receiving medication (24%), with Deflux treatment considered as the least bothersome (19%).
UTI, urinary tract infection; VCUG, voiding cystourethrogram; VUR, vesicoureteral reflux

27. Stenberg and Läckgren 2007, observational study – conclusions
April 17, 2017
Stenberg and Läckgren 2007, observational study – conclusions
Incidence of febrile UTI is low after Deflux
Prevention of febrile UTIs is a primary goal of VUR treatment to reduce the risk of renal damage and long-term consequences
Children view endoscopic injection of Deflux as less bothersome than medication or VCUG
“…there is an excellent long-term success rate in patients initially treated successfully with NASHA/Dx gel [Deflux], with up to 96.6% of patients experiencing no febrile UTIs in the 7–12 years since treatment.”
This study demonstrates that Deflux treatment is associated with a low incidence of febrile UTIs over a follow-up period of 7–12 years, with no confirmed cases in up to 96.6% of patients.
Reduction in the incidence of febrile UTIs is a primary goal of treatment for VUR, to reduce the risk of renal damage and the potential long-term consequences.
Endoscopic injection of Deflux was viewed positively by children and parents alike and was shown to be less bothersome than medication or VCUG.
These findings support the use of endoscopic injection of Deflux as a primary intervention for VUR.
UTI, urinary tract infection; VCUG, voiding cystourethrogram; VUR, vesicoureteral reflux

28. Antibiotics vs endoscopic injection
April 17, 2017
Antibiotics vs endoscopic injection

29. Capozza and Caione 2002, comparison with antibiotics – introduction
April 17, 2017
Capozza and Caione 2002, comparison with antibiotics – introduction
Article type
Original research – Deflux clinical study
Objective
Compare the efficacy and safety of Deflux with antibiotic prophylaxis in children with VUR
Methods
Open, randomised, prospective
1–2 Deflux treatments (STING procedure; n=39) or antibiotic prophylaxis for 12 months (n=21)
Children >1 year of age
Reflux grades II–IV
Follow-up VCUG at 3 and 12 months post-treatment
Full citation
Capozza N and Caione P. Dextranomer/Hyaluronic acid copolymer implantation for vesico-ureteral reflux: a randomized comparison with antibiotic prophylaxis. J Pediatr 2002; 140(2): 230–4.
Article type
Original research – this is an original research manuscript reporting a Deflux clinical study.
Objective
To compare the efficacy and safety of Deflux with antibiotic prophylaxis in children with VUR.
Methods
Open, randomised, prospective design.
A total of 60 children received either Deflux (n=40) or antibiotic prophylaxis for 12 months (n=21).
The children:
were aged >1 years
had VUR grades II to IV
Children receiving Deflux (by STING procedure) received 1–2 treatments; second treatments were received by children with reflux grade ≥II at 3 months (n=11).
A follow-up VCUG was undertaken for all patients at 12 months post-treatment.
STING, subureteric transurethral injection; VCUG, voiding cystourethrogram; VUR, vesicoureteral reflux

30. Capozza and Caione 2002, comparison with antibiotics – results
April 17, 2017
Capozza and Caione 2002, comparison with antibiotics – results
Response rate at month 12 (%)
At month 12, 69% of Deflux patients were cured (reflux grade ≤1) vs 38% in the antibiotic groups (p=0.029)
Response rates at month 12 for ureters with baseline reflux grades of II, III and IV were 95%, 71% and 43% in the Deflux group, vs 37%, 33% and 0% in the antibiotic group.
89% of patients with a positive response at 3 months post-treatment demonstrated a sustained response at month 12.
Only one serious adverse event was observed (fever in the antibiotic group not attributed to study treatment) and there were no safety concerns with either treatment.

31. Capozza and Caione 2002, comparison with antibiotics – conclusions
April 17, 2017
Capozza and Caione 2002, comparison with antibiotics – conclusions
Deflux is more effective than antibiotic prophylaxis for the treatment of childhood VUR
Response to Deflux is sustained for at least 12 months
The benefits of Deflux suggest that it is a useful option for children with VUR
“Patients undergoing successful endoscopic treatment receive immediate protection against further reflux-associated damage”
This study demonstrates that more children can expect to be cured after Deflux treatment than after prophylactic antibiotic treatment.
The study also shows that response to Deflux is sustained over 12 months.
Together with the lack of safety concerns associated with Deflux, the findings of this study show that the therapy is a valuable treatment option for VUR.
VUR, vesicoureteral reflux

32. Koyle et al. 2006, critical appraisal: antibiotics – introduction
April 17, 2017
Koyle et al. 2006, critical appraisal: antibiotics – introduction
Article type
Review – VUR treatment
Objective
Compare antibiotic prophylaxis (long-term use of antibiotics) and endoscopic injection for the treatment of VUR
Points discussed
Clinical efficacy of antibiotic prophylaxis
Implications of long-term antibiotic prophylaxis
Antibiotic resistance
Treatment alternatives for VUR
open surgery
endoscopic injection
Full citation
Koyle MA, Clement M, Cooper CS, Grady R, Kirsch A. Critical appraisal: antibiotic prophylaxis and endoscopic injection for VUR. Issues in Urology 2006; 18(3): 123–30.
Article type
Review article – this is a review article of treatment options for VUR specifically discussing the long-term use of antibiotics (antibiotic prophylaxis) vs endoscopic treatment.
Objective
To compare antibiotic prophylaxis and alternative treatments (open surgery and endoscopic injection) in the treatment of VUR.
Points discussed
The following topics are addressed in the article:
the clinical efficacy of antibiotic prophylaxis
the implications of long-term antibiotic prophylaxis
antibiotic resistance
treatment alternatives for VUR, including open surgery and endoscopic injection.
VUR, vesicoureteral reflux

33. Koyle et al. 2006, critical appraisal: antibiotics – results
April 17, 2017
Koyle et al. 2006, critical appraisal: antibiotics – results
Efficacy of antibiotic prophylaxis
Data supporting the clinical value of antibiotic prophylaxis are limited
Long-term therapy offers no benefit for VUR that fails to respond spontaneously
Implications of long-term antibiotic prophylaxis
Treatment requires serial VCUGs and may still result in surgery or endoscopic intervention
Poor compliance leaves patients vulnerable to infection
Low antibiotic doses used for prophylaxis may promote resistance
Treatment alternatives
Surgery and endoscopic injection are potentially curative
Endoscopic therapy avoids the morbidity and costs associated with surgery
Parents prefer endoscopic treatment over antibiotic prophylaxis or open surgery
Clinical efficacy of antibiotic prophylaxis
Data supporting the clinical value of antibiotic prophylaxis are limited, partly due to ethical considerations concerning the use of a placebo in children (i.e. non-treatment of children at risk of the consequences of VUR).
Antibiotic prophylaxis requires long-term commitment due to the slow resolution of symptoms.
Studies suggest that continuing antibiotic therapy indefinitely offers no benefit for patients in whom VUR fails to respond spontaneously.
Implications of long-term antibiotic prophylaxis
Treatment requires serial VCUGs, yet may still result in surgery or endoscopic intervention if VUR fails to resolve.
Treatment relies on compliance; failure to adhere may leave patients vulnerable to infection.
The low antibiotic doses used for prophylaxis may promote resistance. Previous antimicrobial drug exposure is a major risk factor for infection with drug-resistant pathogens.
Treatment alternatives
Surgery and endoscopic injection are both potentially curative, though surgery is invasive and is associated with high cost and risk of complications (e.g. renal scarring).
Endoscopic therapy addresses many of these concerns, avoiding both the morbidity associated with surgery and the high cost of hospitalisation.
Parental surveys also reveal a preference for endoscopic therapy over both antibiotic prophylaxis and surgery.
VCUG, voiding cystourethrogram; VUR, vesicoureteral reflux

34. Koyle et al. 2006, critical appraisal: antibiotics – conclusions
April 17, 2017
Koyle et al. 2006, critical appraisal: antibiotics – conclusions
Poor compliance and bacterial resistance are concerns with antibiotic prophylaxis for VUR
Endoscopic treatment is a valuable alternative to antibiotic prophylaxis
Endoscopic therapy reduces the need for VCUGs and is associated with minimal morbidity
“The minimally invasive nature of endoscopic therapy offers a viable alternative in the management of VUR”
This review highlights the concerns associated with antibiotic prophylaxis, namely the limited studies supporting its efficacy and the potential of poor compliance to lead to bacterial resistance.
The review explains that endoscopic therapy is a valuable alternative to long-term antibiotic prophylaxis in children with VUR.
The minimally invasive nature of endoscopic therapy suggests that the technique should be used in place of open surgery and antibiotic prophylaxis, and should be considered as the first-line treatment for VUR.
VCUG, voiding cystourethrogram; VUR, vesicoureteral reflux

35. April 17, 2017
Complicated cases

36. Läckgren et al. 2003, double ureters/a small kidney – introduction
April 17, 2017
Läckgren et al. 2003, double ureters/a small kidney – introduction
Article type
Original research – Deflux clinical study
Objective
Assess the efficacy of Deflux for the treatment of primary VUR associated with either double ureters or a small kidney
Methods
Open, retrospective
Children (n=108) aged 7 months to 12.5 years
Primary reflux grade III–V (unilateral or bilateral) associated with either:
double ureter: duplication of a ureter (complete or incomplete separation)
small kidney: one kidney contributing 10–35% of renal function
1–3 Deflux treatments; STING injection
Follow-up VCUG at 3 and 12 months post-treatment
Full citation
Läckgren G, Wåhlin N, Sköldenberg E, Nevéus T, Stenberg Å. Endoscopic treatment of vesicoureteral reflux with dextranomer/hyaluronic acid copolymer is effective in either double ureters or small kidney. J Urol 2003; 170: 1551–5.
Article type
Original research – this is an original research manuscript reporting a Deflux clinical study.
Objective
To assess the efficacy of Deflux for the treatment of primary VUR associated with either double ureters or a small kidney.
Methods
Open, retrospective analysis.
A total of 68 children with double ureters (Group 1) and 40 with a small kidney (Group 2) received Deflux via STING injection between 1993 and 1998.
The children:
were aged between 7 months and 12.5 years
had dilating VUR (unilateral or bilateral reflux grade III or greater) associated with either double ureters (i.e. a duplicated ureter with either complete or incomplete separation) or a small kidney (i.e. one kidney contributing 10–35% of total renal function)
received 1–3 Deflux treatments (Group 1: 2 treatments [41%], 3 treatments [4%]; Group 2: 2 treatments [38%], 3 treatments [10%]).
Follow-up VCUGs were performed at 3 and 12 months post-treatment; long-term follow-up was undertaken over 4–9 years.
STING, subureteric transurethral injection; VCUG, voiding cystourethrogram;
VUR, vesicoureteral reflux

37. Läckgren et al. 2003, double ureters/a small kidney – results
April 17, 2017
Läckgren et al. 2003, double ureters/a small kidney – results
Patients (%)
Group 1 (n=68; double ureters):
overall, 63% of children with double ureters were cured of reflux (defined as reflux grade 0 or I following treatment). There was no correlation between response rate and baseline reflux grade
response rates were 46% for the first procedure and 36% and 67% for the second and third, respectively
only 17 (25%) of patients were referred for open surgery.
Group 2 (n=40; small kidney):
the overall response rate in children with a small kidney was 70%, with no correlation between outcome and baseline reflux grade
response rates were 58% for the first procedure and 33% and 0% for the second and third, respectively
a total of 9 (23%) of patients were referred for open surgery.
A positive response to treatment was sustained throughout follow-up in both groups; of the ureters without reflux at 3 and 12 months, 85% in Group 1 and 86% in Group 2 needed no further treatment.
Deflux was well tolerated in both treatment groups, with no associated complications. UTIs occurred in 14 patients (9 in Group 1 and 5 in Group 2).

38. Läckgren et al. 2003, double ureters/a small kidney – conclusions
April 17, 2017
Läckgren et al. 2003, double ureters/a small kidney – conclusions
Deflux is effective for VUR associated with either double ureters or a small kidney
Results with either double ureters or a small kidney are similar to those observed in patients free from complications
Deflux is a valuable alternative to open surgery for patients with complicated cases of VUR
“Endoscopic Dx/HA copolymer [Deflux] appears to be effective and well tolerated for the treatment of VUR associated with either double ureters or a small kidney”
This study demonstrates that Deflux treatment is effective and well tolerated in complicated cases of VUR associated with either double ureters or a small kidney, a patient group previously considered unresponsive to endoscopic treatment.
Results with double ureters or a small kidney are similar to those previously reported in patients free from complications (63–70% vs 68%; Läckgren et al. 2001)
The findings show that Deflux is a valuable alternative to open surgery, offering immediate and sustained cure without the risks and costs associated with surgical reimplantation.
VUR, vesicoureteral reflux

39. Perez-Brayfield et al. 2004, complex cases – introduction
April 17, 2017
Perez-Brayfield et al. 2004, complex cases – introduction
Article type
Original research – Deflux clinical study
Objective
Assess the efficacy of Deflux for the treatment of complex VUR cases
Methods
Open, prospective
Children (n=72) aged 9 months to 31 years
Mean maximum reflux grade IV/V
1 Deflux treatment using the HIT
Follow-up VCUG at 3 months post-treatment
Full citation
Perez-Brayfield M, Kirsch AJ, Hensle TW, Koyle MA, Furness P, Scherz H. Endoscopic treatment with dextranomer/hyaluronic acid for complex cases of vesicoureteral reflux. J Urol 2004; 172: 1614–6.
Article type
Original research – this is an original research manuscript reporting a Deflux clinical study.
Objective
To assess the efficacy of Deflux for the treatment of complex cases of VUR (i.e. in patients who would otherwise have been referred for open surgery to correct their condition).
Methods
Open, prospective analysis.
A total of 72 children with complex VUR (i.e. VUR with associated complications including persistent reflux after surgery, double ureters and neurogenic bladder) received Deflux treatment between 2001 and 2003.
The children:
were aged between 9 months and 31 years (mean 5.6 years)
had a mean maximum reflux grade of IV or V
had persistent VUR or recurrent VUR despite antibiotic therapy, had failed to comply with antibiotics or had new renal scarring
received 1 Deflux treatment using the HIT.
Follow-up VCUGs were performed at 3 months post-treatment.
HIT, hydrodistention implantation technique; VCUG, voiding cystourethrogram;
VUR, vesicoureteral reflux

40. Perez-Brayfield et al. 2004, complex cases – results
April 17, 2017
Perez-Brayfield et al. 2004, complex cases – results
Response rate (patients, %)
Follow-up data at 3 months post-treatment were available for 69 patients.
Factors complicating the VUR cases were: persistent reflux after surgery (n=17); neurogenic bladder (n=9); double ureters (n=15); retained stump (n=6); Hutch diverticula (n=6); ureterocele (n=5); ectopic ureter (n=7); and posterior urethral valve, epispadias, urogenital sinus and prune belly syndrome (n=1 for each).
The overall success rate (defined as reflux grade 0) was 68%.
A variation in the success rate was observed between the complications. For example, Deflux injection was successful in 88% of patients who had failed open surgery and 73% of patients with a double ureter.
The treatment was well tolerated in all patient groups, with no cases of post-treatment kidney infection or urinary retention reported.
Supporting notes
Neurogenic bladder = a problem with the nerves that control the bladder.
Hutch diverticula = weakness in the bladder wall near the ureter leading to a diverticulum (a bulge or outpouch).
Ureterocele = swelling of one of the ureters near the bladder.
Epispadias = defect in the location of the opening of the urethra.
Urogenital sinus = birth defect in which the urethra and vagina open into a common channel.
Prune belly syndrome = a birth defect associated with physical problems including abnormal development of the urinary tract.
Complicating factors

41. Perez-Brayfield et al. 2004, complex cases – conclusions
April 17, 2017
Perez-Brayfield et al. 2004, complex cases – conclusions
Deflux can be effective in patients with complex VUR
Deflux is well tolerated in children with VUR associated with a range of complications
Deflux provides an alternative to open surgical correction of VUR in patients with complications
“This minimally invasive approach is warranted as an initial step in the management of complex cases of vesicoureteral reflux”
This study demonstrates that Deflux treatment can be effective in patients with complex VUR for whom open surgery would previously have been the only option.
Deflux treatment is well tolerated in such patients.
Deflux treatment is an alternative treatment option for complex cases of VUR – open surgery remains available for patients in whom this less-invasive treatment is unsuccessful.
VUR, vesicoureteral reflux

42. Läckgren et al. 2007, VUR and bladder dysfunction – introduction
April 17, 2017
Läckgren et al. 2007, VUR and bladder dysfunction – introduction
Article type
Original research – Deflux clinical study
Objective
Assess the efficacy of Deflux for VUR with bladder dysfunction
Methods
Open, retrospective
Children with VUR and bladder dysfunction (n=54) aged 2–15 years
Reflux grade II–V
1–3 Deflux treatments using STING
Follow-up VCUG at 3 and 12 months post-treatment
Long-term follow-up for 7–12 years
Full citation
Läckgren G, Sköldenberg E, Stenberg A. Endoscopic treatment with stabilized nonanimal hyaluronic acid/dextranomer gel is effective in vesicoureteral reflux associated with bladder dysfunction. J Urol 2007; 177: 1124–8.
Article type
Original research – this is an original research manuscript reporting a Deflux clinical study.
Objective
To assess the efficacy of Deflux for the treatment of children with VUR associated with bladder dysfunction.
Methods
Open, retrospective study.
A total of 54 children with VUR and bladder dysfunction received Deflux treatment between 1993 and 1998.
The children:
were aged between 2 and 15 years
had VUR grades II–V
received 1–3 Deflux treatments using STING.
Follow-up VCUGs were performed at 3 and 12 months post-treatment.
Patients were followed long term, for 7–12 years after treatment (long-term follow-up data were obtained by communication with parents, primary care physicians and review of patient charts).
A follow-up questionnaire was sent in 2005 asking about patients’ bladder condition, experiences of treatment and number of UTIs occurring post-treatment.
Supporting notes
Resolution of VUR was defined as VUR grade 0 or I at the last VCUG.
Resolution of bladder dysfunction was classified as no problems reported on patient charts and in questionnaire responses.
STING, subureteric transurethral injection; VCUG, voiding cystourethrogram;
VUR, vesicoureteral reflux

43. Läckgren et al. 2007, VUR and bladder dysfunction – results
April 17, 2017
Läckgren et al. 2007, VUR and bladder dysfunction – results
Resolution rate after last Deflux treatment (patients, %)
VUR 83
Bladder dysfunction 59
UTIs
No VUR, bladder dysfunction or UTIs 56
Overall, VUR was corrected (grade ≤1) in 45 patients (83%).
According to patient charts, 32 patients (59%) reported no bladder problems and 45 (83%) had no UTIs after the last Deflux treatment.
Taken together, the most frequent outcome of treatment was resolution of VUR and bladder dysfunction with no UTIs occurring during follow-up (30 patients, 56%).
Questionnaire results were similar to the data obtained from patient charts.
No treatment-related adverse events were reported.
UTI, urinary tract infection

44. Läckgren et al. 2007, VUR and bladder dysfunction – conclusions
April 17, 2017
Läckgren et al. 2007, VUR and bladder dysfunction – conclusions
Deflux appears to be effective and well tolerated in children with VUR and bladder dysfunction
Success rates and number of post-treatment UTIs are comparable in patients with and without bladder dysfunction
These findings suggest that bladder dysfunction should not be considered a contraindication to Deflux treatment
“This study supports treating patients with concurrent bladder dysfunction and VUR with endoscopic injection……”
This study demonstrates that children with bladder dysfunction associated with their VUR can be effectively treated with Deflux.
Compared with previous studies of Deflux in children without bladder dysfunction:
resolution rates in children with VUR and bladder dysfunction are equivalent
there is no notable increase in treatment-related complications or adverse events, and no increase in the number of post-treatment UTIs in children with bladder dysfunction.
UTI, urinary tract infection; VUR, vesicoureteral reflux

45. April 17, 2017
Parental preference

46. Capozza et al. 2003, parental preference – introduction
April 17, 2017
Capozza et al. 2003, parental preference – introduction
Article type
Original research – parental preference study
Objective
Assess informed parental preference when choosing between antibiotic prophylaxis, open surgery and endoscopic treatment for VUR
Methods
Cross-sectional
Parents of children (n=100; mean age 4 years) with reflux grade III
Detailed information provided on antibiotic prophylaxis, open surgery and endoscopic treatment (efficacy, mode of action, potential complications)
Questionnaire circulated asking which treatment they would choose
Full citation
Capozza N, Lais A, Matarazzo E, Nappo S, Patricolo M, Caione P. Treatment of vesico-ureteral reflux: a new algorithm based on parental preference. BJU Int 2003; 92: 285–8.
Article type
Original research – this is a parental preference study.
Objective
To assess informed parental preference when choosing between antibiotic prophylaxis, open surgery and endoscopic treatment for the treatment of their children with VUR.
Methods
Cross-sectional analysis.
Parents of children (n=100) with reflux grade III who had received antibiotic prophylaxis for ≥6 months took part in the study.
The mean age of the children was 4 years (range 1 to 15 years).
Parents were provided with detailed information on antibiotic prophylaxis, open surgery and endoscopic treatment, including modes of action, cure rates, possible complications and advantages and disadvantages.
Parents were presented with a questionnaire to confirm that they understood the treatment options and asking which treatment they would choose.
VUR, vesicoureteral reflux

47. Capozza et al. 2003, parental preference – results
April 17, 2017
Capozza et al. 2003, parental preference – results
Undecided 13%
Antibiotics 5%
Endoscopic
injection 80%
Open surgery 2%
The vast majority of patients preferred endoscopic treatment (80%) over open surgery (2%) or antibiotic prophylaxis (5%) for treatment of their children with VUR; the remaining 13% could not decide.

48. Capozza et al. 2003, parental preference – conclusions
April 17, 2017
Capozza et al. 2003, parental preference – conclusions
The majority of parents would choose endoscopic injection over open surgery or antibiotic prophylaxis to treat VUR in their children
Endoscopic treatment should be considered as first-line therapy for persistent VUR
“We propose a new treatment algorithm for VUR, with endoscopic treatment as first-line therapy for most patients with persistent reflux.”
This study demonstrates that, if given the choice, the vast majority of parents would select endoscopic injection over open surgery or antibiotic prophylaxis to treat VUR in their children, probably due to its less invasive nature.
On this basis, the authors state that endoscopic treatment should be considered as first-line therapy for persistent VUR, with open surgery being reserved for severe cases of VUR, or those not responding to endoscopic treatment.
VUR, vesicoureteral reflux

49. April 17, 2017
Resolution

50. Schwab et al. 2002, spontaneous resolution – introduction
April 17, 2017
Schwab et al. 2002, spontaneous resolution – introduction
Article type
Original research – review of patient records
Objective
Determine the spontaneous resolution rate of VUR
Methods
Retrospective review of 179 girls and 35 boys with VUR during 1981–1984
bilateral reflux n=109; dysfunctional voiding n=60
mean age: 4.2 years (3 months to 15.8 years)
median follow-up: 3 years
Patients categorised by worst grade of reflux and maintained on antibiotic prophylaxis
VCUG undertaken annually until reflux resolved
Spontaneous resolutions rates per reflux grade were calculated using Kaplan-Meier curves
Full citation
Schwab CW, Wu H-Y, Selman H, Smith GHH, Snyder HM, Canning DA. Spontaneous resolution of vesicoureteral reflux: a 15-year perspective. J Urol 2002; 168: 2594–9.
Article type
Original research – this is an original research article reporting data from a review of patient records.
Objective
To determine the spontaneous resolution rate of VUR for each reflux grade by patient.
Methods
Retrospective review of 179 girls and 35 boys presenting with a UTI during 1981–1984 and diagnosed with VUR:
of these patients, 107 had bilateral reflux and 60 had dysfunctional voiding.
Mean age at presentation was 4.2 years (range 3 months to 15.8 years) and median follow-up was 3 years.
Patients were categorised by the worst grade of reflux and were maintained on antibiotic prophylaxis.
Patients were followed until they underwent surgery, discontinued antibiotics or were withdrawn. VCUGs were undertaken annually until reflux was resolved.
Resolution rate per reflux grade was calculated using Kaplan-Meier curves (a well-known, scientific method of analysing data from clinical trials).
VCUG, voiding cystourethrogram; VUR, vesicoureteral reflux

51. Schwab et al. 2002, spontaneous resolution – results
April 17, 2017
Schwab et al. 2002, spontaneous resolution – results
Resolution rate
(patients, %)
Overall, reflux grades I to III resolved at 13%/year for the first 5 years, then decreased to 3.5%/year for the remaining 10 years. Grade IV reflux resolved at 5%/year throughout the study.
The overall resolution rates for reflux grades I, II, III and IV were 83.3%, 76.8%, 68.4% and 35.5%, respectively, with estimated median years to resolution of 2.7, 3.1, 4.5 and 9.5 years, respectively.
Bilateral reflux resolved more slowly than unilateral reflux (p=0.012) and VUR resolved more rapidly in boys than in girls (p<0.0005).
Dysfunctional voiding had no effect on the overall rate of reflux resolution (p=0.47).
Years to resolution:

52. Schwab et al. 2002, spontaneous resolution – conclusions
April 17, 2017
Schwab et al. 2002, spontaneous resolution – conclusions
VUR can take a number of years to resolve, particularly in severe cases
Various factors influence the likelihood of spontaneous resolution of VUR, including:
initial reflux grade (grades I–III tend to resolve more quickly)
unilateral vs bilateral reflux (bilateral reflux can be expected to take longer to resolve)
gender (tendency for VUR to resolve more rapidly in boys)
This study demonstrates that spontaneous resolution of VUR can take many years to occur, during which time, children remain at risk of the potential consequences of a febrile infection (pyelonephritis) in the presence of VUR.
Certain factors affect the chances of spontaneous resolution, these include:
initial reflux grade – mild cases (grade I–III) tend to resolve more quickly than more severe grades
unilateral vs bilateral reflux – bilateral reflux was found to take longer to resolve
gender – reflux resolved more slowly in girls than in boys.
“While resolution can occur at any time, the more important decision is whether a patient remains at risk for morbidity due to renal scarring or pyelonephritis”
VUR, vesicoureteral reflux