Vesicoureteral reflux

VUR DIAGNOSIS AND MANAGEMENT

1. Vesicoureteral Reflux evaluation and management 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 The prevalence of reflux was estimated to be approximately 30% for children with UTI and 17% without infection. Reflux may be present in up to 70%of infants who present with UTI 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 76% of refluxing infants are male (Ring et al, 1993). In later life, the likelihood of having reflux, presenting with a UTI is higher in male than female. 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 One difference established over several studies is the relative 10-fold lower frequency of reflux in female children of African descent. 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.

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

26. 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.

27. 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.

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

29. 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.

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

31. 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.

32. 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

33. 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

34. 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.

35. 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 .

36. 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 .

37. 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.

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

39. Associated anomalies 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

40. 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.

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

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

43. 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

44. 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%

45. 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.

46. 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.

47. 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 .

48. 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

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

50. 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

51. 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 .  -

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

53. 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.

54. I nfrahiatal 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.

55. 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

56. 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.

57. 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)

58. 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 .

59. 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

60. 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

61. 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%.

62. 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

63. Deflux Dextranomer / Hyaluronic Copolymer (DX/HA) is formed of crosslinked dextranomer microspheres (80 to 250 μ m 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.

64. 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 10-100 μ m. Malizia demonstrated in experimental studies that the particles can migrate to regional lymph nodes and to distantorgans including the lung and the brain

65. 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 ,

66. 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%.

67. Thank You