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Vesicoureteral Reflux:
Updates and Guidelines
Hiep T. Nguyen, MD FAAPTrans: Joao ABA Barbosa, MD
Department of Urology
Childrens Hospital Boston/ Harvard Medical School
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Over 30 years ago
In 1974, when askedabout Reflux, Sir DavidInnes Williams replied :
Reflux is old hat : now that wehave a reliable operation tofix it, it is a boring subject to
talk about!
Courtesy of S. Bauer, M.D.
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Vesicoureteral Reflux in 2011
Historical perspective
Categories of VUR
The link between UTIs and VUR
Evaluation of VUR
Goals of VUR management
How to measure success in managing VUR
Current approaches to VUR The future of VUR
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Past History of VUR
Galen recognized the valvular action of the UVJ.
1903: Sampson described ascending infections from bladder to kidneydue to reflux, later confirmed by Bompus (1924).
1916: Kretschmer study on cystography, reflux present in 4/11 children.
1930: MF Campbell noted VUR present in 12% of children studied with
cystogram. 1950-1960s: Hutch, Paquin, Litch, Gregoire, Politano etcTechniques
for surgical correction of VUR.
1960: Association of VUR with Chronic Pyelonephritis described byHodson.
1965: Recognition of intrarenal reflux by Brodeur. 1984: Ransley/Risdon Big-Bang theory confirmed experimentally in
piglet model.
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Recent History of VUR
1960s and 1970s: recognition of spontaneous VUR resolution withage (Baker et al. 1966, Edwards et al. 1977).
1960s: control of UTIs with low-dose antibiotic therapy, Smellie et al.
1979: Koff, Lapides et al. observe association of VUR and bladder
dysfunction. 1980: Merrick, use of DMSA for renal imaging.
Early 1980s: Birmingham Reflux study and IRS.
1984: Bouton, distinction between dysplasia and chronicpyelonephritis aka renal scarring.
1980s: International grading system for VUR. 1984: Puri-ODonell popularize the STING
1997:AUA VUR Guidelines.
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UVJ
Kidney
Bacteria
VUR
Embryology
(dysplasia)
Voiding dysfunction
GeneticsAge
Anatomy
(intrarenal reflux)
Host factors Virulence Resistanc
Antibiotics
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So What is Vesicoureteral Reflux?
Familial, polygenic condition characterized byregurgitation of urine from bladder up into the upper
urinary tract as demonstrated by VCUG or RNC
May be associated with a spectrum of renal parenchymallesions with or without a history of infection
Several categories of VUR seem to exist
25,000 patient visits to urologists per year
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Categories of Primary Reflux
Neonatal VUR (prenatal hydro, males, high-grade,rapid resolution, renal lesions; ?CAKUT)
Young girl VUR (UTIs, females, lower grades,variable resolution rates, voiding dysfunction, renallesions rare)
Sibling VUR (screening, UTIs and renal lesionsrare, spont. resolution)
VUR in duplex systems (CAKUT)
Megacystis-megaureter complex(CAKUT)
Each one may need to be managed differently
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UTI, VUR and Renal Injuries
9
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Sequelae of Renal Injury
10
Renal dysfunction/
failure
Hypertension
most common cause(Dillon, 1975)
23-30% with scarring
develops
hypertension
pathogenesis: renin-
angiotensin system
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UTI, VUR and Renal Injury Association between UTI and VUR recognized
but not cause and effect
UTI may cause renal lesions but these are knownto occur without VUR
Pyelonephritis is not always associated with renallesions
Renal lesions may be present with no history ofUTIs
Can patients at risk, i.e. prone to renal lesions inthe face of UTIs and VUR be identified?
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So What is the Controversy? Not all children who develop a UTI have VUR
Approximately 25-35%
Work up many to find a few?
VUR resolve on its own Dependent on patient characteristics and
genetics
Evaluation for VUR is not completely benign
12
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Evaluation of VUR
VCUG or RNC only modalities to diagnose VUR Indications for evaluation in flux
Invasive and difficult studies esp. in older children
Timing of follow-up study not well established
Radiation exposure
Risk of iatrogenic infection
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Current Management of VUR
Options include:
non-surgical approach with prevention of UTIs,with or without antibiotic prophylaxis.
Surgical options, open or endoscopic.
VS. VS.
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Current Management of VUR
No consensus but AUA guidelines published in1997 and updated 2011.
There have been NO prospective randomizedtrials comparing efficacy and risk-benefit ratios foreach options.
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VUR and the Urologist:
What do I do Now?
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Spontaneous Resolution of VUR
17
?
?
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VUR and Resolution Rates Based upon patient characteristics/ genetics
18
Estrada et al., 2009
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Goals of VUR Management
Improve voiding to prevent urinary stasis and high
intravesical pressures
Prevention of ascending infections and/or
pyelonephritis
Prevent renal scarring Prevent HTN and renal failure
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Goals of VUR Management
How successful have we been so far?
Can we do better?
The answers depends on what
are the outcomes we are
looking for/ measuring.
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What are the Outcomes Measures
for VUR studies ?
Eradication of VUR
Is that really the issue?
Prevention of UTIs/pyelonephritis.
Requires long-term F/U to ascertain true results.
Prevention of potentially severe consequencesof VUR (renal lesions, chronic HTN and ESRD).
Requires very long-term, longitudinal studies.
Identification of those patients at risk for long-term consequences.
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Risks and VUR
Failure to recognize and treat VUR can lead to seriousconsequences in (relatively) small number of patients.
Evaluation and treatment of VUR does offer some risks
(allergic reaction, UTI, radiation, anesthesia, surgical
complications etc). Proactive value of screening for VUR in selected patients.
Has the treatment of VUR had a positive impact on
children over the last 40 years?
YES, but impact is hard to quantitate. But can we do better?
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Current Management of VUR
Depends on clinical setting. Identification of patients at risk for renal lesion
Requires proper evaluation (cystogram, DMSA
scan).
Recognition and treatment of voiding
dysfunction and constipation.
Thorough discussion with parents/care givers of
options. Follow-up mandatory
Id tifi ti f P ti t t Ri k
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Identification of Patients at Risk
for Renal Lesions
Family history of UTIs and VUR
Higher grades of VUR
Renal lesions on DMSA scan
Young age History of recurrent UTIs/pyelonephritis
Carriers of chromosomal anomalies (ACE
DD genotype, KLK1, TNF polymorphism)associated with renal scarring
Other features yet to be defined
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Options in the Treatment of VUR
Watchful Management
Antibiotics Therapy
Open Surgical Correction Endoscopic Correction
25
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Watchful Management of VUR Protocol:
No antibiotic prophylaxis Careful and consistent toileting with prevention
of disorders of elimination
Yearly monitoring with renal U/S
Who: Reasonable for older, toilet-trained children with
lower grades of VUR I- III
Family must be compliant
Switch to other modality of management ifUTIs
Duration of Treatment: ????
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Chemoprophylaxis for VUR Protocol:
Low dose antibiotics Advantages:
Time tested
Low rates of complications
Risk-benefit ratio low
Low cost
Disadvantages:
Not always well tolerated
Issues of compliance
Antimicrobial resistance (how often?)
Addition of probiotics
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Chemoprophylaxis for VUR
Who: Grade II-III: Controversial
Grade IV-V: Likely benefits
Family must be compliant
Switch to other modality of management if UTIs
Duration of Treatment: When to stop?
Open Surgical and Laparoscopic
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Open Surgical and Laparoscopic
Therapy for VUR
Protocol: Several Techniques: Open and laparoscopic
Advantages:
Time tested
Good efficacy in eradicating VUR Low complication rates
Disadvantages:
Complications can be severe
Requires anesthetic/ hospital stay Expensive
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Open Surgical and Laparoscopic
Therapy for VUR Who:
Grade 2-5 with
Breakthrough UTI
Non-compliance with other therapy
Progressive US or DMSA changes Non-resolution (>3 yrs ?)
? Family / Surgeons Preference
Duration: finite treatment time but need follow up
Long-term outcomes:
? Rate of infection may not be completely reduced
? Long-term benefits/ problems
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Endoscopic Treatment for VUR
Protocol: Injection of Deflux/ Macroplastique
Advantages:
Technically straight forward
Very low complication rates Complications are minimal
No hospitalization
Disadvantages:
Less efficacious in eradicating VUR than open surgery(especially in higher grades)
Expensive
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Endoscopic Treatment for VUR
Who:
Same indication as open/ laparoscopic surgery
Duration: finite treatment time
Long-term outcomes: No long-term studies demonstrating durability
requires F/U cystogram
Impact on long-term consequences of VUR
unknown
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Conclusions
The evaluation and treatment of VUR is evolving Long-term, prospective, randomized studies are
needed comparing various therapeutic options
Current management guide-lines should to be
updated
Parents and patients should be made aware of
all therapeutic options, advantages and
disadvantages, risks and complications Long-term follow-up is mandatory for all patients
with evidence of renal involvement
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The Future
Genetic basis of VUR better defined(chromosomal loci)
Reclassification of VUR based on genetics
Identification of renal markers associated withrenal lesions (urine proteomics)
Determination of risk factors for UTI
predisposition and/or renal damage allowing for
better patient selection for Rx Refinement in therapeutic approaches targeted
towards patients at risk
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