3 DEFINITION A retrograde flow of bladder urine into the upper urinary tract.
4 DEMOGRAPHICS Prevalence - 10% in general population. - 70% in infants with UTI.- 30% in children with UTI% asymptomatic infants with Antenatal hydronephrosis.
5 GENDAR- VUR usually high grade and bilateral in boys compared with girls.- Seventy six percent of refluxing infants in male( Ring et al, 1993 ).- Even though the great majority (85%) of prevailing reflux in older children occurs in females.
6 DEMOGRAPHICAgeIncidence of Reflux in Patients with Urinary Tract InfectionsAge (yr) Incidence (%)<Adults
7 INHERITANCE AND GENETICS Sibling Reflux - The prevalence of VUR in siblings to be approximately 32% ( Hollowell and Greenfield, 2002 ). - Screening? - 75% are asymptomatic.
8 Reach to 100% in identical twin siblings; (Kaefer et al, 2000 ) INHERITANCE AND GENETICSSibling RefluxReach to 100% in identical twin siblings; (Kaefer et al, )The genetic mode of transmission may be autosomal dominant.
9 INHERITANCE AND GENETICS Genes Involved A prospective screen of the progeny of refluxing patients revealed a 66% rate of reflux in the offspring ( Noe et al, 1992 ),PAX 2 , chromosome 10q: mutations involving renal anomalies (dysplasia, hypoplasia) and VUR.
10 INHERITANCE AND GENETICS Genes Involved Glial-derived neurotrophic factor (GDNF) and it’s receptor RET: over expression of RET in mice leads to abnormal placement of the ureteral bud with 30% VUR at birth.
11 INHERITANCE AND GENETICS Genes Involved Uroplakin III gene (UPK3) depletion: only in animal and fatal in humans. Angiotensin receptor 2 (AGTR2): implicated in renal and ureteral developmental anomalies (UPJ obstruction, Megaureter).
12 FUNCTIONAL ANATOMY OF THE ANTIREFLUX MECHANISM A balance of several factors; 1- functional integrity of the ureter UVJ allow intermittent passage of a urinary bolus fashion from the ureter into the bladder and prevent the retrograde flow of bladder urine back toward the upper tracts during storage and micturition.
13 FUNCTIONAL ANATOMY OF THE ANTIREFLUX MECHANISM 2-anatomic composition of the UVJThe ureter enters the bladder wall with an oblique intramural path (intramural ureter) and extends through a submucosal tunnel of appropriate length (submucosal ureter) to open onto the trigone in a correct location.
14 FUNCTIONAL ANATOMY OF THE ANTIREFLUX MECHANISM 2-anatomic composition 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's sheath. The latter contributes to formation of the deep trigone. The middle circular ureteral muscle ends at the level of the hiatus. The inner longitudinal ureteral fibers form the superficial trigone.
15 FUNCTIONAL ANATOMY OF THE ANTIREFLUX MECHANISM The intramural ureter remains passively compressed by the bladder wall during bladder filling to prevent urine from entering the ureter Flap-valve’ . Adequate intramural length plus fixation of the ureter between its extravesical and intravesical points is required to create this antirefluxing compression valve.
16 The UVJ in children revealed an approximate 5:1 ratio of tunnel length to ureteral diameter in nonrefluxing junctions versus a 1.4:1 ratio in refluxing UVJs ( Paquin, 1959 ).
17 Mean Ureteral Tunnel Length and Diameter in Normal Children Age (yr) I Mean Ureteral Tunnel Length and Diameter in Normal Children Age (yr) I.U.L (mm) S.U.L (mm) U.D at UVJ (mm) From Paquin AJ: Ureterovesical anastomosis: The description and evaluation of a technique. J Urol 1959;82:573.I.U.L: intravesial ureteral lengthS.U.L:submucosal ureteral lengthU.D: ureteral deameter at UVJ
18 FUNCTIONAL ANATOMY OF THE ANTIREFLUX MECHANISM functional compliance of the bladder The existence of local efferent and afferent neuromuscular coordination between the UVJ and the periureteric bladder wall is suggested by neurophysiologic studies that induce an elevation or decrease in intraluminal UVJ pressure during bladder filling ( Shafik, 1996 ).
19 ETIOLOGY OF VESICOURETERAL REFLUX Primary Reflux Represents a congenital defect in the structure and therefore the function of the UVJ Reflux occurs despite an adequately low-pressure urine storage profile in the bladder The length-diameter ratio of the intramural ureteral tunnel is almost always less than 5:1 ratio.
20 ETIOLOGY OF VESICOURETERAL REFLUX Secondary refluxIn normal, mature urinary tract, increasing the intravesical pressure alone does not necessarily induce VUR.
21 ETIOLOGY OF VESICOURETERAL REFLUX Secondary reflux Secondary obstruction can be due to anatomical; ureterocele, uretheral stenosis or PUV. OR functional ; neurogenic bladder, non-neurogenic neurogenic bladder, bladder instability.
22 ETIOLOGY OF VESICOURETERAL REFLUX Secondary refluxAnatomical Causes of Secondary Reflux;PUV:Most common cause,Reflux is present in 48% to 70% of patients with PUVs.Relief of PUV obstruction appears to be responsible for resolution of reflux in one third of patients only.
23 ETIOLOGY OF VESICOURETERAL REFLUX Secondary reflux Anatomical Causes of Secondary Reflux; In females, anatomic bladder obstruction is rare. The most common structural obstruction is from a ureterocele that prolapses into the bladder neck ( Merlini and Lelli Chiesa, 2004 )
24 ETIOLOGY OF VESICOURETERAL REFLUX Secondary reflux Functional causes Poorly compliant bladder along with its abnormal interaction with dyssynergic urinary sphincters can lead to increase interavesical pressures which then weakens and alters the UVJ to cause VUR. McGuire established a strong correlation of bladder pressure more than 40 cmH2O with VUR raised to 80% in patients with neurogenic bladder.
25 ETIOLOGY OF VESICOURETERAL REFLUX Secondary reflux Functional causes Increase in bladder voiding pressures, continence is exchanged for incomplete emptying. Gradual distortion of bladder and UVJ architecture. Structural failure of the UVJ is a critical determinant in creating secondary VUR.
26 ETIOLOGY OF VESICOURETERAL REFLUX Secondary refluxFunctional Causes of Secondary Reflux;UTI: ureteral atonylessens compliance, increases intravesical pressures, distorting and weakening the UVJ ;transient VUR can appear during UTI and resolve after treatment.
27 International Classification of Vesicoureteral Reflux Grade DescriptionI Into a nondilated ureter.II Into the pelvis and calyces without dilatation.III Mild to moderate dilatation of the ureter, renal pelvis, and calyces with minimal blunting of the fornices.IV Moderate ureteral tortuosity and dilatation of the pelvis and calyces.V Gross dilatation of the ureter, pelvis, and calyces; loss of papillary impressions; and ureteral tortuosity.
29 DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX - Antenatal hydronephrosis. - UTI. - Fever; VUR present in 56% of patients less than 6months and temp Renal scarring can occur with a single UTI, even in the absence of a fever.
30 DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX Radiographic investigation for VUR has generally been directed to; - Children with UTI and younger than 5 years, - All children with a febrile UTI regardless of age, - Any male with a UTI regardless of age or fever.
31 DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE LOWER URINARY TRACT Cystographic Imaging The basis of reflux detection lies in demonstrating the retrograde passage of an imaging contrast material from the bladder to the ureter and pelvicalyceal system.
32 DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE LOWER URINARY TRACTCystographic ImagingVCUG-provides information on both the functional dynamics and the structural anatomy of the urinary tract.-Static images record bladder contour, the presence of diverticula or ureteroceles, the grade of reflux, the configuration and blunting of calyces, and intrarenal reflux.-Passive or active reflux is demonstrated dynamically during fluoroscopy while filling and voiding.
36 DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE LOWER URINARY TRACTCystographic ImagingRadionuclide Cystogram:- Reduces radiation exposure.- More sensitive in some cases.- Greater role in follow up.- Bladder wall trabeculation, diverticuli, ureteral duplications and posterior urethral valve cannot be seen.
39 DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE upper URINARY TRACTRenal Sonography- Nonionizing, noninvasive imaging platform- Quantitative assessment of renal dimensions,which can then be used to monitor renal growth over time.
40 u/s Rt. Kidney in pt. with g II reflux In Rt. Duplex system
41 DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE upper URINARY TRACTDi-mercapto-succinic acid (DMSA);- The gold standard for imaging functioning renal parenchyma.- Document congenital dysplasia.- Assessment of renal growth and development- Need 2 studies separated by 8-12 weeks to differentiate pyelonephritis from scar.
45 DIAGNOSIS AND EVALUATION OF VESICOURETERAL REFLUX ASSESSMENT OF THE UPPER URINARY TRACTMagnetic Resonance Imaging:- Used with gadolinium based contrast material.- Diagnose reflux, and assess renal parenchymal scarring.- Catheter to introduce contrast.- Not sensitive.- Need sedation.- Child cannot void during study.
46 Congenital Renal Scarring CORTICAL DEFECTSRenal scarringCongenital Renal Scarring Grade of VUR Normal Slight Damage Severe DamageI-III (100%)IV (53%) (34%) (13%)V (15%) (38%) (46%) Adapted from Marra G, Barbieri G, Dell'Agnola CA, et al: Congenital renal damage associated with primary vesicoureteric reflux. Arch Dis Child Fetal Neonatal Ed 1994;70:F147.
47 CORTICAL DEFECTS Acquired Renal Scarring Reflux provides a mechanical hydrodynamic mechanism that facilitates the ascension of micro- organisms from the bladder to the kidneys. As such, reflux may be considered an accelerant for renal tissue infection after bacterial colonization of the bladder.
48 Factors important for acquired renal scarring; Grade The frequency of scarring itself appears to be directly proportional to the grade of reflux with which it is associated ( Winter et al, 1983 ; Weiss et al, 1992b ). Age The greatest risk for postinfectious renal scarring occurs within the first year of life ( Winberg, 1992 ). The kidney's predilection for postpyelonephritic scarring is inversely proportional to age. Scarring may still occur beyond 5 years of age ( Smellie et al, 1985 ; Benador et al, 1997 ).
49 Factors important for acquired renal scarring; Age scarring in older children is frequently the result of late diagnosis, delayed or inadequate treatment of infection, and social factors that often interfere with patient management. Adults with pyelonephritis and normal urinary tract rarely have scarring.
50 Complication of renal scarring; Hypertension, % of children with reflux nephropathy. - Related to reflux grade, scarring severity and bilaterality. - Correction of reflux alone is unlikely to ameliorate blood pressure ( Wallace et al, 1978 ).
51 Complication of renal scarring; Renal failure and End stage renal disease The incidence of chronic pyelonephritis as a primary cause of end-stage renal disease has fallen from 15% to 25% to less than 2% ( North American Pediatric Renal Transplant Committee, 2004). Reflux remains a leading cause of chronic renal failure in children and young adults in Italy, 25%; mostly > grade III, and 75% are boys.
52 Complication of renal scarring; Reflux Nephropathy It is a radiographic findings: - Focal parenchymal thinning over clubbed calyx. - Calyceal dilation with parenchymal thinning. - Impaired renal growth. - Directly related to grade of reflux.
55 ASSOCIATED ANOMALIES AND CONDITIONS Ureteropelvic Junction Obstruction The incidence of VUR associated with UPJ obstruction ranges from 9% to 18%. Conversely, the incidence of UPJ obstruction in patients with reflux ranges from 0.75% to 3.6%. High-grade reflux being five times more likely than lower grades of reflux to be associated with UPJ obstruction.
56 ASSOCIATED ANOMALIES AND CONDITIONS Ureteral Duplication; - VUR is the most common abnormality associated with complete ureteral duplication. - Weigert and Meyer Role. - Even in the absence of obstruction from a ureterocele or ureteral ectopia, duplication with low-grade reflux may take longer to resolve than in single-system reflux
57 ASSOCIATED ANOMALIES AND CONDITIONS Bladder Diverticula; Cause reflux by 2 ways First, paraureteral diverticulum could compromise the antireflux configuration of the UVJ and cause reflux. Second and more rarely, a large paraureteral diverticulum could expand within Waldeyer's fascia and cause ureteral obstruction.
58 ASSOCIATED ANOMALIES AND CONDITIONS Bladder Diverticula; Reflux associated with paraureteral diverticula resolves at rates similar to those of primary reflux and should be managed according to the prevailing indications for the reflux itself, irrespective of the diverticulum.
59 ASSOCIATED ANOMALIES AND CONDITIONS multicystic dysplastic kidney (MCDK)In the largest series to date, 75 patients with MCDK had a 25% prevalence (19 patients) of contralateral reflux, and half of these were low grade (I to II) ( Miller et al, 2004).Spontaneous resolution occurred in a mean of 4.4 years, regardless of grade.Only one patient had reflux corrected surgically.
60 Pregnancy and Reflux Bladder tone decreases because of edema and hyperemia, changes that predispose the patient to bacteriuria. In addition, urine volume increases in the upper collecting system as the physiologic dilatation of pregnancy evolves.
61 MANAGEMENT Goals of Therapy - Protect upper tract by preventing pyelonephritis. - Preserve existing renal function in children with renal impairment.
62 MANAGEMENT Principles of Management 1 MANAGEMENT Principles of Management 1. Spontaneous resolution of reflux is very common. 2. High-grade reflux is less likely to resolve spontaneously. 3. Sterile reflux is benign. 4. Extended use of prophylactic antibiotics is benign. 5. The success rate with surgical correction is very high.
63 MANAGEMENT Spontaneous Resolution Resolution by Grade Most cases of low-grade reflux (grade I and II) will resolve. 63% of grade II ( Duckett, 1983 ), 80% of grade II ( Arant, 1992 ), 85% of grade II (Edwards et al, 1977)
64 MANAGEMENT Spontaneous Resolution Resolution by Grade - Grade III reflux will resolve in approximately 50% of cases ( Duckett, 1983 ; McLorie et al, 1990 ). - Very few cases of higher-grade reflux (grades IV and V and bilateral grade III) will resolve spontaneously, with not more than 25% ( Weiss et al, 1992 ).
65 MANAGEMENT Spontaneous Resolution Resolution by Age - Resolution rate 20% per year; ( Connolly et al, 2001). - The study by Skoog and associates (1987) observed that reflux resolved in 30% to 35% of subjects each year.
67 No scarring at diagnosis; MANAGEMENTNo scarring at diagnosis;Grade I-II VUR medical managementgrade III-IV VURYounger children medical management.especially with unilateralolder children surgery only if bilateral orif does not improved.
68 No scarring at diagnosis; MANAGEMENTNo scarring at diagnosis;Grade V VURnewborns andyoung children medical management initially if able to stay on antibioticsolder children surgerygirls with persistent VUR surgeryto prevents complications from future pregnancies
69 Scarring at diagnosis; Grade I-II medical management Grade III-IVUnilateral medical managementbilateralyoung children medical managementolder surgeryGrade VNewborns medical manangement initially> 1 year surgery
70 MANAGEMENT In newborn patients, it is reasonable to wait until approximately 5 years of age, assuming that no intercurrent breakthrough infections occur. Beyond this age, the kidneys become less prone to scarring after pyelonephritis ( Olbing et al, 2003 ).
72 Follow up Assessment - Urine C/S every 3months Follow up Assessment - Urine C/S every 3months. - Yearly radiologic studies. - Thompson 2005; proposed that a VCUG every other year for lower grades VUR (I, II); and every 3 years in higher grades VUR (III, IV, V).
73 Follow up Assessment Upper Tract assesment U/S and/or DMSA If there is no symptomatic UTI, it is highly unlikely that new scar will develop.If there is reflux nephropathy, serum creatinine should be assessed regularly.
74 SURGICAL MANAGEMENT indications for antireflux surgery; -breakthrough UTIs despite prophylactic antibiotics. -noncompliance with medical management -severe VUR (grade IV or V) esp. with pyelonephritic changes. -failure of renal growth, new scars, or worsening renal function -VUR persisting in girls. -VUR associated wih congenital abnormalities of the UVJ (bladder diverticulae).
75 Breakthrough UTI Pyelonephritis during antibiotic prophylaxis. Risk OF Breakthrough UTI:- Girls receiving prophylaxis for recurrent UTI.- Refluxing patient with voiding dysfunction.- Uncircumcised boys with reflux.- Children with scarring on DMSA, in both sexes.
76 Breakthrough UTI Breakthrough UTI is an indication of failure of non-surgical management. Surgical therapy should be considered.
77 Surgical Principles of Reflux Correction • Exclusion of causes of secondary VUR. • Adequate mobilization of the distal ureter without tension or damage to its delicate blood supply. • Creation of a submucosal tunnel that is generous in caliber and satisfies the 5:1 ratio of length to width.
78 Surgical Principles of Reflux Correction • Attention to the entry point of the ureter into the bladder (hiatus), the direction of the submucosal tunnel, and the ureteromucosal anastomosis to prevent stenosis, angulation, or twisting of the ureter. • Attention to the muscular backing of the ureter to achieve an effective antireflux mechanism. • Gentle handling of the bladder to reduce postoperative hematuria and bladder spasms.
79 Surgical Principles of Reflux Correction Cystoscopy cystoscopy in the course of conservative management of VUR is indicated only to confirm or manage abnormalities found on other imaging modalities ( Ferrer et al, 1998 ).
80 Surgical Principles of Reflux Correction Cystoscopy Some surgeons choose to perform cystoscopy at the time of surgery after induction of anesthesia. This is helpful in identifying subtle anomalies not detected on preoperative imaging, particularly if an extravesical technique is used and the bladder is not opened.
86 Intravesical approach; Glenn-Anderson Repair Intravesical approach; Glenn-Anderson Repair. - Less obstruction or kinking, as ureter remains in original hiatus. - Best candidates are those whose ureters are laterally positioned.
90 Surgical Management of VUR complications of ureteral reimplantation Early - VUR due to trigonal edema, usually low grade and transient, treated conservatively. - Obstruction due to edema, bleeding, bladder spasms, mucus plugs or clots. Treated with NT or stent if does not resolve.
91 Surgical Management of VUR Complications of ureteral reimplantation Late - VUR - Failure to achieve sufficient submucosal length or failure to provide adequate muscular backing: (the most common cause). - Failure to tailor dilated ureter - Failure to identify and treat secondary causes of VUR. Treatment: intravesical reimplantation, mucosa of old tunnel incised and scars sharply removed.
92 Surgical Management of VUR Complications of ureteral reimplantation Late - Obstruction Due to ischemia, angulation at hiatus, inadvertent passage through peritoneum or viscera.
95 Definition; Ureters wider than 7 to 8 mm can all be considered MGUs ( Hellstrom et al, 1985 ). Primary MGU more common in boys than girls, has a slight predilection (1.6 to 4.5 times) for the left side, and is bilateral in approximately 25% of patients. In up to 10% to 15% of children the contralateral kidney may be absent or dysplastic.
97 Refluxing Obstructed Megaureter A small group of patients have an element of obstruction combined with reflux. Primary refluxing obstructed megaureter occurs in the presence of an incompetent VUJ that allows reflux through an adynamic distal segment.
98 Six-month-old infant with bilateral massive reflux and obstructive.
99 Mild obstructed megaureter, showing fullness of the pelvic ureter, normal proximal ureter, and calyces
100 Two-month-old boy with bilateral megaureters Two-month-old boy with bilateral megaureters. A, DTPA renal scan bilateral hydronephrosis and megaureters;left ureter incompletely filled. B, left retrograde pyelogram immediately prior to surgical correctionNote the sharp cut-off at the distal ureter. C, Following transvesical mobilization of the megaureters.The longitudinal channel vessels are preserved and seen through the periureteral adventitia.D, Postoperative pyelogram following bilateral ureteral plication of the lower half of each megaureter and cross-trigonal ureteroneocystostomy.E, Follow-up radionuclide renal scan.
101 A, Intravenous pyelogram (IVP) at two months of age, moderate left reflux megaureter. B, IVP at seven months of age, progressive ureteral dilation.C, IVP at nine months of age, worsening hydroureteronephrosis.D, Voiding cystourethrogram, massive reflux.E, Postoperative IVP, improved kidney, and ureteral dilatation. Radiologicdeterioration despite maintaining sterile urine.
102 An infant presenting with abdominal distention and uremia. A, IVP shows nonvisualization of the right kidney and severe left hydronephrosis and ureteral tortuosity.B, Cystogram shows bladder trabeculation, right reflux, and outward displacement of the ureterwith filling of a small periureteral saccule.C, Voiding film, urethral valves, and complete bladder emptyingwith residual dye filling the bladder saccules and right reflux.D, IVP following transurethral resection of the valves, bilateral total ureteral tapering ,and reimplantation, a satisfactory result.
103 antenatal hydronephrosis, UTI, abdominal pain,hematuria. Evaluation of the megaureter- Presentation:antenatal hydronephrosis, UTI, abdominal pain,hematuria.- Urine analysis and C/S.- U/S.- VCUG.- MAG3 or DTPA.- Whitaker test.
104 PRINCEBLE OF MANAGMENT When renal function is not significantly affected and UTIs do not become a major problem, expectant management is preferred Antibiotic suppression with close radiologic surveillance is appropriate in most cases.
105 PRINCEBLE OF MANAGMENT When Hydroureteronephrosis is severe and shows no signs of improvement In cases in which there is a documented decrease in renal function In patients with recurrent febrile infections despite prophylaxis, surgical correction is undertaken when technically feasible, usually between the ages of 1 and 2 years
106 PRINCEBLE OF MANAGMENT For the occasional newborn patientsalternative options includea distal cutaneous loop ureterostomy provides a simple, temporary, low- morbidity solution for poor drainage until the child is old enough to undergo reimplantation.temporary drainage with an internal ureteral stent.
107 Management Refluxing, non-obstructed primary medical management for infants, continued if trend towards improvement seen surgery for older with persistent high-grade reflux endoscopic subureteric injection is recommended. secondary treat secondary cause.
108 Management Non-obstructed, non-refluxing primary Medical management as long as renal function is not affected as UTIs not a problem US q3-6mo surgical correction by age of 1-2 if no improvement or severe hydronephrosis. secondary Treat secondary cause. Antenatal MGU Observe: most will resolve.
109 Surgical correction of MGUs - Plication or infolding techniques(Starr and Kalicinski). useful for moderately dilated ureter increased complications if plicate ureter > 1.75cm in diameter. - Excisional techniques useful for severely dilated or thickened ureter.
110 Technique of ureteral plication and cross-trigonal reimplantation. A, Transvesical mobilization of megaureter.B, Following ureteral plication.C, Placement of the plicated ureter in a submucosal tunnel.D, Fixation of the ureter to contralateral wall of bladder.E, Method of ureteric plication (Starr).
113 Complication Complications can occur regardless of whether excisional tapering or a folding technique is used - Stenosis - Reflux
114 Ureteral obstruction related to postoperative edema percutaneous nephrostomy and antegrade stenting). If persistent, the usual cause is ureteral ischemia, revision and excision of the ischemic segment followed by reimplantation.