1. Vesicoureteral reflux (VUR) occurs when urine flows backward from the bladder into the ureters and kidneys. This document discusses the history, demography, causes, diagnosis, evaluation, natural history and management of VUR. 2. VUR is more common in younger children, males, and those with urinary tract infections. The prevalence is higher in siblings of children with VUR. 3. VUR can be primary due to structural issues or secondary due to bladder dysfunction. Grading depends on extent of reflux during cystography. 4. Management focuses on antibiotics to prevent infections while allowing for spontaneous resolution, which is more likely for lower grades of

1. By Dr Sumit Gupta
Moderator: Prof. Ak.Kaku.singh

2. History
 Vesicoureteral reflux (VUR) represents the retrograde flow
of urine from the bladder to the upper urinary tract
 Galen and da Vinci:
- First references to VUR by Western medicine
- UVJ as a mediator of unidirectional flow of urine
from the kidneys to the bladder
 Hutch(1952): Relationship between VUR and chronic
pyelonephritis in paraplegic patients
 Hodson(1959):UTI and renal scarring carried a high
likelihood of VUR in children

3. Demography
 Prevelance
1. The prevalence of reflux was estimated to be
approximately 30% for children with UTI and 17%
without infection.
2. Reflux may be present in up to 70%of infants who
present with UTI
3. In asymptomatic infants, the prevalence of reflux ranges
from 15% in infants with absent or mild hydronephrosis
on postnatal ultrasound to 38% in a group of neonates
with various postnatal upper tract sonographic anomalies
including hydronephrosis, renal cysts, or renal agenesis.

4.  Gender
1. 76% of refluxing infants are male (Ring et al, 1993).
2. In later life, the likelihood of having reflux,
presenting with a UTI is higher in male than female.
3. Even though the great majority (85%) of prevailing
reflux in older children is in females
 The reason of high incidence in male is high UTI rate
in uncircumcised male

5.  Age
Even in the presence of infection or asymptomatic
bacteriuria, reflux is more common in younger patients
Incidence of Reflux in Patients with Urinary Tract
Infections
 AGE (yr) INCIDENCE (%)
<1 70
4 25
12 15
Adults 5.2

6.  Race
1. One difference established over several studies is the
relative 10-fold lower frequency of reflux in female
children of African descent.
2. In addition, reflux resolved sooner in this
population.

7. Inheritance
Sibling Reflux
 Prevalence of VUR in siblings to be approximately 32%
 However, the prevalence may be as low as 7% in older
siblings or as high as 100% in identical twin siblings.
 This finding supports the notion that VUR can be an
inherited condition and that the genetic mode of
transmission may be autosomal dominant.

8. Now the concern arises if screening should be
done in asymptomatic sibling????
Because it is renal consequences of reflux that are at
issue, rather than reflux itself, siblings may be better
served by noninvasively screening for cortical
abnormalities first, before screening for reflux itself.

9. Top down approach in sibling
 By imaging the kidneys first followed by assessing the
integrity of the ureterovesical junctions.
 Such an approach helps to strike a balance between
the invasive nature of reflux detection versus first
detecting existing renal cortical abnormalities that
might be the result of past or ongoing reflux.
 Considering the age and renal integrity combined, a
possible graded approach to screening is developed for
siblings older or younger than 5 years of age,with or
without renal structural abnormalities

10.  Thus in siblings 5 years or older with normal kidneys,
little would be gained from detecting reflux and is
treated to a febrile UTI in the usual fashion as for the
general pediatric population.
 In siblings 5 years or older with renal abnormalities,
the suggestion would be of past or continuing reflux.
Ruling the diagnosis in or out by cystography could
then be done.

11.  The sibling younger than 5 years of age with normal
kidneys would be managed on the basis of clinical
judgment regarding likelihood for infection rather than an
immediate need to diagnose reflux.
 The sibling younger than 5 years with cortical renal defects
would have the most to lose by a febrile infection in the
face of reflux and risk of additional cortical loss following
reflux-induced pyelonephritis triggered by an infection.
 In this case, knowledge of the potentially higher prevalence
of reflux in siblings would logically obtaining a screening
cystogram.

12. Genes involved
 Probably many genes are involved:
- PAX2
- GDNF-RET
- UPK3
- AGTR2-ACE
 No specific gene product or functional role for these
loci in reflux has yet been identified

13. Functional Anatomy of the
Antireflux Mechanism
 Factors Include the functional integrity of the ureter,
the anatomic composition of the ureterovesical
junction (UVJ), and the functional dynamics of the
bladder.
First, for purposes of reflux prevention, the ureter
represents a dynamic conduit, which adequately
propels the urine presented to it in a bolus fashion,
antegrade, by neuromuscular propagation of
peristaltic activity. In so doing, reflux is actively
opposed.

14. The second component is the anatomic design of the
UVJ.
 At the extravesical bladder hiatus, the three muscle layers
of the ureter separate.
 The outer ureteral muscle merges with the outer detrusor
muscle to form Waldeyer sheath. The latter contributes to
formation of the deep trigone.
 The intramural ureter remains passively compressed by the
bladder wall during bladder filling, preventing urine from
entering the ureter.
 Adequate intramural length and fixation of the ureter
between its extravesical and intravesical points is required
to create this antirefluxing compression valve.

15.  Paquin’s early dissections of the UVJ in childre n
revealed an approximately 5 : 1 ratio of tunnel length
to ureteral diameter in non refluxing junctions
compared with a 1.4 : 1 ratio in refluxing UVJs.

16.  A refluxing ureterovesical junction has the same
anatomic features as a nonrefluxing orifice, except for
inadequate length of the intravesical submucosal
ureter.

17. Causes of VUR
 Primary Reflux:
- fundamental deficiency in the function of the UVJ
- bladder and ureter remain normal or non
contributory.
- reflux occurs despite an adequately low-pressure
urine storage profile in the bladder
- length-diameter ratio is almost always less than that
described by Paquin( ie : 5:1)

18.  Secondary reflux:
- normal function of the UVJ being overwhelmed
- bladder dysfunction : congenital, acquired, or
behavioral.
- considered secondary if absence was documented at
some point before its detection

19. Anatomical causes:
 PUV’s - The most common anatomic obstruction of
the bladder in the pediatric population is posterior
urethral valves (PUVs). Reflux is present in 48% to
70% of PUV patients .
- Ureteroceles
- Ureteral duplication

20.  Neuro-functional causes:
- Neurogenic bladder – Spina bifida
- Infant voiding patterns
- Dysfunctional voiding
- Uninhibited bladder contractions is the most common
urodynamic abnormality associated with reflux in
neurologically normal children. In one study of 37 girls
with “primary” reflux, 75% had uninhibited
contractions.
- Constipation

21. BBD
 In older children, acquired abnormalities in voiding
parameters commonly known as bladder and bowel
dysfunction have been associated with reflux.
 The precise cause of voiding dysfunction is variable
but may evolve from a persistence of the expected early
attempts to suppress bladder contractions during the
toilet training months by volitional contraction of the
external sphincter.
 If this behavior becomes prolonged or intensifies,
bladder voiding pressures increase leading higher UTI
risk and VUR.

22.  American Urological Association (AUA) Panel on VUR
Guidelines now suggests that bladder and bowel
dysfunction (BBD) is by far one of the most critical
and modifiable variables that affect VUR management
and attendant UTIs.
 Various study analysis now indicates that BBD is
associated with a higher incidence of UTIs while on
antibiotic prophylaxis, as well as after surgical
correction of VUR, with less VUR resolution at 24
months from diagnosis and with reduced success of
endoscopic surgery.

23. Grading of VUR

24. Radionuclide Classification(RNC)
 Low grade = grade 1-3
 High grade = grade 4-5
 RNC does not provide discrete images of the ureteral
and calyceal architecture required to assign reflux
grade, classifying reflux by RNC is difficult.

26. Clinical features
 Features of recurrent UTI:
- Fever
- Flank pain
- pyuria.
 Palpable renal mass
 Delayed growth
 Weight loss

27. Diagnosis & Evaluation
Confirmation of Urinary Tract Infection
 Confirming and documenting true UTI is paramount
in the appropriate management of the patient with
reflux.
 Many variables are responsible for the accurate
assessment and interpretation of UTI in the context of
reflux.
 These include clinical history and presence of fever;
age of the patient; circumcision status; method of
urine specimen collection, storage, and delivery; and
the results of urine dipstick and microscopic analyses.

28. Evaluating UTI
 The probability of finding VUR in children with a UTI
is 29% to 50% .
 Radiologic investigation of the patient with UTI is
tailored to those patients who are placed at greatest
renal functional risk from the presence of VUR.
 For this reason, radiographic investigation for VUR has
generally been directed to children younger than 5
years old, all children with a febrile UTI, and any male
with a UTI regardless of age or fever, unless sexually
active.

29.  AAP tightens the recommendation for voiding
cystography to follow second rather than initial febrile
UTI for children under 2 years of age.

30. Assesment of lower urinary tract
Cystographic imaging
 The voiding cystourethrogram (VCUG) and
radionuclide cystogram (RNC) therefore are the two
common forms of direct cystography and constitute
the present-day gold standard approaches to reflux
detection.

31. VCUG
 Provides information on :
- functional dynamics
- structural anatomy
 Parameters observed:
A. Static films
- bladder contour
- presence of diverticula
- ureteroceles
- grade of reflux
- configuration & blunting of calyces
- bladder neck anatomy
- urethral patency.

32. B. Dynamic films:
- active reflux
C. Delayed or postvoid films:
- Crucial in documenting clearance of contrast from
the upper tracts
- Dilated PCS + Retained contrast = PUJO
 Contraindicated in active cystitis
- Exceptions: In children with a h/o recurrent
pyelonephritis and repeatedly negative voiding
studies in the intercurrent periods.

34. Radionuclide cystogram
 Radiation exposure 1% of VCUG
 Little anatomic detail is afforded
 Ideal for:
- screening
- monitoring the natural history of Disease.
- surgical follow-up of reflux
 Greater sensitivity in grades II to V reflux
 Grade I reflux into distal ureter  poorly detected

35. Uroflowmetry & Urodynamic study
 full pressure-volume urodynamic studies of the bladder
are not required in all reflux patients, a minimal survey of
bladder emptying characteristics can be obtained by
uroflowmetry.
 In refluxing patients, it is important to establish whether
the bladder outlet is functioning relatively normally or
harbors more resistive characteristics .
 Lack of smoothness of the flow-velocity curve shows
incomplete relaxation of the bladder outlet that delays the
natural history of reflux resolution or even promots reflux.
 Increased PVR may be a risk factor for UTI

36. Top down approach
 The top-down approach is an interesting concept
based on the notion that only clinically relevant reflux
with potential to cause renal injury is worthy of
uncovering.
 Only a dimercaptosuccinic acid (DMSA) renal scan is
obtained following a febrile UTI, with cystography
reserved only for patients with abnormal scintigraphy.
 Children with a negative DMSA require no further
evaluation unless they develop recurrent UTI, in which
case a VCUG should be obtained.

37. Cystoscopy
 Routine use is not mandated.
 Role immediately prior to surgery for confirming:
- orifice position
- duplication
- proximity of diverticula to the orifice
- urethral patency
- endoscopic Mx(DEFLUX)
 A recently developed, although still controversial
cystoscopic modality termed the PIC technique
(Positioning of the Instillation of Contrast at the UO)
purports to detect reflux under general anesthesia in
patients with a history of febrile UTIs but a normal VCUG.

38. Assessment of the upper urinary
tract.
Renal Sonography
 The mainstay of renal imaging in VUR management is
ultrasonography
 Quantitative assessment of renal dimensions :
- used to monitor renal growth
- impact of any intercurrent febrile episode on renal
growth
- need for further assessment of renal function by
scintigraphy or the need for correction of reflux
 Degree of corticomedullary differentiation .

39.  Modern enhancements in ultrasound technology
permit imaging of perfusion abnormalities in tissue.
 In reflux nephropathy using color Doppler
ultrasound, renal resistive index measurements
derived from blood flow in interlobar and arcuate
arteries are significantly increased in higher grades of
reflux and correlate positively with scintigraphic
findings from the same renal unit.

40. Renal Scintigraphy
 DMSA:
- detection of reflux-associated renal damage
- acute pyelonephritic changes
- follow-up of reflux

41. Associated anomalies
1. PUJ Obstruction
- incidence of VUR associated with PUJO = 9% - 18%
- the incidence of PUJO in patients with reflux = 0.75%
to 3.6%
- incidence with high-grade reflux = five times more
likely than lower grades of reflux

42. Ureteral duplication:
- VUR is the most common abnormality associated
with complete ureteral duplication.
- reflux occurs most commonly into the lower pole.
 This relationship is based on the studies of Weigert
and Meyer, who documented the more lateral and
proximal insertion of the lower pole ureter associated
with a shorter intramural ureter at VUJ.

43. Bladder diverticulae:
- Outpouching of mucosa between detrusor muscle
bundles without any true muscle backing itself
- Cause of reflux:
paraureteral diverticulum

44. 4.Renal anomalies:
- Renal agenesis: 46% association
- MCDK: 28% association
- Presence mandates VCUG
5. Megacystis-Megaureter syndrome:
- More common in males
- Differentiation from PUV

45. Natural history and management
 Spontaneous resolution:
- At birth, the probability of spontaneous resolution of
primary reflux is inversely proportional to the initial
grade
- If a patient is encountered at a later age, resolution
from any point in time forward will depend on the
initial grade of reflux

46.  Resolution by grade:
- Most cases of low-grade reflux (grade I and II) will
resolve : 63-85%
- Grade III reflux will resolve in approximately 50% of
cases
- Higher-grade reflux (grades IV and V and bilateral
grade III) : 9-25%

47.  Resolution with age :
- Age has greater significance than grade
- Most prevalent in neonates and young children and will
demonstrate the greatest tendency to resolve in this group
 The study by Skoog and colleagues (1987) observed that
30% to 35% of subjects resolved their reflux each year.
 Younger patients (<12 months old) resolved more quickly,
with grade 3 requiring slightly more time than grade 2 to
resolve.
 The traditional period of observation for resolution is 5
years, probably because the greatest proportion of growth
and anatomic remodeling of the UVJ is complete.

48. Management
 Principles of management:
1. Spontaneous resolution of reflux is very
common
2. High-grade reflux is less likely to resolve
spontaneously.
3. Extended use of prophylactic antibiotics &
“ Watchful waiting”
4. The success rate with surgical correction is very
high.
5. Sterile reflux is benign.

49.  The classic approach has been to offer daily low-dose
prophylactic antibiotic suppression of infections as the first
line of treatment under the principle that every case of
reflux should be offered time to resolve spontaneously,
despite grade.
 Clearly, age at presentation and grade will factor into
predicting when and if resolution is likely to occur.
 In addition, in patients diagnosed after one or more
episodes of pyelonephritis, the presence of scarring on
renal scintigraphy may temper a decision for extended
prophylaxis and observation, particularly if scarring is
extensive, the reflux is high grade, renal function is already
depressed.

50. Medical management
 “watchful waiting” while maintaining urinary
sterility through the judicious use of single daily low-
dose antimicrobial prophylaxis.
 Often, antibiotics are given as oral suspensions once
per day and preferably at night.
 Nighttime dosing allows for antibiotic concentration
in the bladder urine over the longest period .
 Breakthrough febrile UTIs or pyelonephritis while on
antibiotic prophylaxis are generally considered an
indication for termination of watchful waiting and
correcting the reflux

51.  Once the radiographic resolution of reflux has been
documented,antibiotic prophylaxis is terminated,
usually a few days after the cystogram.
 This also is the precise time for reinforcing a lifelong
adoption of good toileting and bladder behaviors.

52. Surgical management
ABSOLUTE INDICATIONS :
 Breakthrough urinary tract infections
 Failure of medical management
 - patient noncompliance
 - persistance of reflux with prolonged medical management.
 - progressive deterioration in renal function.
 Ureteral obstruction assoc with VUR
 Refluxing ureter opening into bladder diverticulum
 Cystoscopic observation of golf hole orifice
RELATIVE INDICATIONS :
 Presence of massive reflux – gr IV & V
 Reflux associated with paraureteral diverticulum
 In girls whose reflux persists after they have reached the full somatic
growth potential at puberty.
 Parental preference

53. The principles of surgical correction :
- Exclude secondary reflux
- Adequate ureteral mobilization without tension and protection
of the ureteral blood supply
- A generous submucosal tunnel should be fashioned
- Attention should be directed to prevent angulation and twisting
- Bladder tissues must be handled gently
-attention to muscular backing of ureter to achieve effective anty
refux mechanism.
-creation of submucosal tunnel that satisfy 5:1 ratio of length and
width recommended by Paquin.
-

54. According to approach :
 Intravesical
 Extravesical
 Combined
According to the position of the sub mucosal
tunnel in relation to the original hiatus :
 Suprahiatal
 Infrahiatal

55. Supra hiatal tunnel
 Politano-Leadbetter Technique
 The principle behind this technique, which was
originally described by Politano and Leadbetter (1958),
is to bring the ureter in through a new hiatus superior
to the original insertion.
 A submucosal tunnel is created in the direction of the
trigone, medial to the original orifice.
 The advantage of this technique is that a long tunnel
can be created, which is valuable in the higher grades
of reflux.

57. Infrahiatal
 Glenn-Anderson Technique
 In 1967 Glenn and Anderson described their technique
of ureteral reimplantation .
 By using the same hiatus and advancing the ureter
distally toward the bladder neck, the potential
complications associated with thePolitano-Leadbetter
technique, specifically kinking of the ureter, are
avoided
 The distance from the hiatus to the bladder neck limits
the length of the tunnel.

59. Cohens cross trigonal technique.
 Intravesical, infrahiatal procedure
 Simple, safe and most commonly used
 Good for small capacity bladder
 Success > 95%
Problem :
 Difficult retrograde catheterization of ureters

61. Extra vesical procedure.
Lich –Gregoir techique.
 The advantage of the extravesical technique is that the
bladder is not opened; thus postoperative hematuria
and bladder spasms are minimized.
 The technique is simple to learn.
 The main concern with this technique has been the
development of transient voiding inefficiency that is
seen in up to 20% of cases.

62. Follow up
 Discharged on uro-prophylaxis
 Monitoring of pt’s
- BP
- renal function
- urine analysis
 Follow up USG and urine c/s after 6-12 weeks.
 VCUG after 3 mnths
 Discontinuation of uroprophylaxis on resolution of
reflux
 DMSA after 1 yr (not mandatory)

63. complications
Persistent Reflux.
 Early reflux following ureteroneocystostomy is usually not
a significant clinical problem and commonly resolves by 1
year on repeat cystography.
Contralateral reflux
 Seen in 5-11% cases
 There was no difference noted among the various surgical
techniques, but there was a significant trend toward
development of contralateral reflux with the higher grades
of ipsilateral corrected reflux and correction of reflux in
duplex systems.

64.  Prophylactic bilateral reimplantation for unilateral
reflux, to avoid contralateral reflux, is not warranted
on the basis of the high spontaneous resolution rates.
Obstruction
 Due to odema , clot ,twisting or kinking of ureter.
 Diagnosis made by USG showing severe HDUN.
 PCN or stenting has to be done.
 Redo surgery may be required

65. Endoscopic management
 Injection of a bio- compatible bulking agent beneath
intravesical portion of ureter in sub-mucosal tunnel
 Elevates the intra-vesical ureter  narrowing of lumen
 Prevents regurgitation of urine & allows antegrade
flow

67. ADVANTAGES
 OPD based treatment
 less morbidity, no mortality
 No surgical scar
 Success rate almost equivalent to open surgery for
primary reflux.
DISADVANTAGES
 Cost
 Lower success rate compared to surgery for high
grade reflux,upto 90%.

68. Agents used for Endoscopic Correction of Vesicoureteral
Reflux
Nonautologous Materials
 Polytetrafluoroethylene (PTFE)
 Cross-linked bovine collagen
 Polydimethylsiloxane
 Dextranomer hyaluronic copolymer (Deflux)
 Coaptite
Autologous Materials
 Chondrocytes
 Fat
 Collagen
 Muscle

69. Deflux
 Dextranomer/Hyaluronic Copolymer (DX/HA) is formed of
crosslinked dextranomer microspheres (80 to 250 μm in
diameter) suspended in a carrier gel of stabilized sodium
hyaluronate.
 DX/HA is biodegradable, the carrier gel is reabsorbed, and the
dextranomer microspheres capsulated by fibroblast migration
and collagen ingrowth.
 DX/HA loses about 23% of its volume beyond 3 months of
follow-up
 The appeal of Deflux is that it is a natural product that is easily
administered without a ratcheted syringe through a smaller-gauge
needle.
 It is currently the preferred agent for endoscopic correction in
most centers.

70. Polytetrafluoroethylene Paste
(Teflon Paste)
 Teflon paste is relatively inexpensive; it is viscous and
requires a ratcheted syringe for injection.
 Less used now because of concerns regarding distant
migration of the PTFE particles.
 Particle size 10-100μm.
 Malizia demonstrated in experimental studies that the
particles can migrate to regional lymph nodes and to
distantorgans including the lung and the brain

71. Polydimethylsiloxane (Macroplastique)
 Polydimethylsiloxane (PDS) is a solid silicone
elastomer that has been used as a soft tissue bulking
agent.
 The main advantage of PDS is that it is a permanent
material that remains well encapsulated, causing
minimal local inflammatory changes.
 PDS has yet to achieve FDA approval for correction of
VUR possibly because of concerns regarding
migration, particularly particles that are smaller than
80 μm,

72. Laparoscopic Surgical Procedures
Gil-Vernet Procedure
 In this procedure the trigonal mucosa is incised
vertically and themtwo ureters are approximated into
the midline with a single submucosal suture.
 This procedure has been accomplished
laparoscopically transvesically with limited sucees
 Reported success rates of 60%.

73. Thank You