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Vesicoureteral Reflux
Pediatric Conference 9/18/2006
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Vesicoureteral Reflux (VUR)
Definition Retrograde flow of urine from the bladder through the incompetent UV valve Low-pressure reflux VUR that occurs during bladder filling High-pressure reflux VUR that occurs during micturition May occur during bladder filling, voiding or both
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Incidence Estimated at >10% Incidence of VUR in children with a UTI
Less than 1 year of age: 70% 4 years old: 25% 12 years old: 15% Adult: % Percent decrease likely due to spontaneous resolution, resulting from bladder growth and elongation of the ureteral tunnel 17.2% prevalence in children without UTI hx
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Incidence Infants with antenatally detected VUR show a male preponderance 85% of VUR detected later in life occurs in females Males presenting with UTI are more likely to have VUR Boys tend to present at younger age 25% during the first 3 months of life Often have more severe reflux During first few months of life, uncircumcised males are 10x more likely to have a UTI.
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Incidence As much as 80% of prenatally dx’d VUR occurs in boys
Usually high grade and bilateral in boys Caucasian 10x > African-American Grade and percent who resolve spontaneously equal once diagnosed
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Etiology - Primary VUR Congenital anomaly of the UVJ
Deficiency of the longitudinal muscle of the intravesical ureter results in an inadequate valvular mechanism Length of the intramural ureter to ureteral orifice diameter 5:1 normally Less than 5:1 ratio, reflux occurs
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Etiology - Secondary VUR
Bladder obstruction and increased pressure Anatomic causes Posterior Urethral Valves (50% have VUR) Most common anatomic cause Ureteroceles (can obstruct bladder neck)
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Etiology - Secondary VUR
Functional causes - more common in both sexes Neurogenic bladder Spina bifida, sacral agenesis Nonneurogenic neurogenic bladder Acquired due to abnormal voiding patterns in a neurologically normal child Bladder instability Most common urodynamic abnormality associated with VUR
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International Classification
Based upon contrast in the ureter & renal pelvis during VCUG Grade I: Ureter only Grade II: Ureter, pelvis, calyces, no dilation, normal calyceal fornices Grade III: Mild or moderate dilation and/or tortuosity of the ureter, and mild or moderate dilation of the pelvis, but no or slight blunting of the fornices Grade IV: Moderate dilation and/or tortuosity of the ureter and mild dilation of renal pelvis and calyces; complete obliteration of sharp angle of fornices but maintenance of papillary impressions in majority of calyces, but no or slight blunting of the fornices Grade V: Gross dilation and tortuosity of ureter; gross dilation of renal pelvis and calyces; papillary impressions are no longer visible in majority of calyces
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Grade I- ureter only
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Grade II-Ureter, pelvis, calyces, no dilation, normal calyceal fornices
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Grade III-Mild or moderate dilation and/or tortuosity of the ureter, and mild or moderate dilation of the pelvis, but no or slight blunting of the fornices
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Grade IV- Moderate dilation and/or tortuosity of the ureter and mild dilation of renal pelvis and calyces; complete obliteration of sharp angle of fornices but maintenance of papillary impressions in majority of calyces, but no or slight blunting
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Grade V- Gross dilation and tortuosity of ureter; gross dilation of renal pelvis and calyces; papillary impressions are no longer visible in majority of calyces
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Grade I- ureter only
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Grade II-Ureter, pelvis, calyces, no dilation, normal calyceal fornices
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Grade III-Mild or moderate dilation and/or tortuosity of the ureter, and mild or moderate dilation of the pelvis, but no or slight blunting of the fornices
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Grade IV- Moderate dilation and/or tortuosity of the ureter and mild dilation of renal pelvis and calyces; complete obliteration of sharp angle of fornices but maintenance of papillary impressions in majority of calyces, but no or slight blunting
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Grade V- Gross dilation and tortuosity of ureter; gross dilation of renal pelvis and calyces; papillary impressions are no longer visible in majority of calyces
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VCUG and US in newborn
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VCUG: Bilateral reflux
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Demographics of Reflux
Grade I: 5-8% Grade II: 35% Grade III: 25-35% Grade IV: 15-25% Grade V: 5% 50% of children with reflux will have bilateral VUR
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Secondary VUR Treatment of Secondary VUR often allows spontaneous resolution Treatment goals are to decrease uninhibited contractions and lower pressure Ditropan contributes to resolution and downgrading of VUR in 62%
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Secondary VUR Strong association between intravesical pressures > 40cm H20 and VUR in MM and NGB VUR resolved or decreased in 55% of patients if leak point pressures < 40 If significant PVR is present, bladder emptying is necessary Normal children without NGB Double and timed voiding Relaxation techniques Biofeedback Intermittent catheterization with anticholinergics If medical management fails to decrease pressure, urinary diversion or augmentation may be necessary
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Presentation & Diagnostic Evaluation
Most VUR patients present with infection Newborn: Failure to thrive, lethargy Older children: Fever, dysuria, frequency, lethargy, GI symptoms Urine Culture in any child with fever or malaise Bag: most common, least reliable (high false positive with contamination from skin and rectum) Mid-stream urine: if toilet-trained Catheterization = preferred Suprapubic aspiration = most sensitive
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Etiology of VUR - Lower UTI
Bladder inflammation decreases compliance VUR occurs due to increased pressure and distortion of the UVJ Gram negative endotoxins can cause ureteral atony Some delay VCUG until UTI resolved Avoid false positive Sometimes VUR occurs only with UTI Some perform while on antibiotics VUR seen in % of children with UTI 30% already have evidence of parenchymal scar Scarring can occur after 1 UTI Fever not always present
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Diagnosis VCUG and Renal U/S performed in:
Any child < 5 with documented UTI Any child with febrile UTI regardless of age Any boy with UTI unless sexually active If no anatomic abnormalities are found Reassurance that UTIs do not pose serious threat to upper urinary tract Improve toilet hygiene
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Cystography VCUG Important to evaluate presence of VUR during filling and voiding Evaluate UVJ and urethra, post void, delayed images for drainage Accuracy is improved by repeating several cycles of voiding and filling Nuclear cystography Less anatomic detail than VCUG Helpful during follow-up Less radiation (100-fold less)
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Nuclear Cystography Grade 1,2, and 3 Reflux
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Upper Tract Assessment
Ultrasound Diagnostic study of choice in the initial evaluation of the upper tracts Cannot rule out reflux Assesses bladder and kidneys Renal size Parenchymal thickness Presence of scars, hydro, renal or ureteral anomalies Recommended annually for patients medically managed for VUR, to detect evidence of scarring
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IVP Less commonly used Roughly measures function
Assess presence of scars and parenchymal thinning
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Renal Scan DMSA used to assess for pyelonephritis and cortical renal scars 98% specific 92% sensitive in detection of renal scars Valuable when pyelonephritis is suspected but has not been proved
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DMSA Scan: scarring in right kidney
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Cystoscopy Limited role in diagnosis of VUR
Orifice configuration does not predict VUR Indications for cystoscopy Nonvisualization of entire urethra on cystogram Uncertain about ureteral location or anomaly Inconclusive radiographic definition of lower or upper tracts Localization of paraureteral diverticulum Performed in concert with planned surgical repair Identify location of ectopic ureter Paraureteral diverticulum
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Post-Infectious Scarring
VUR predisposes the kidney to ascending UTI Pyelonephritis often occurs without VUR Patient Age Risk of scarring greatest < 1 year Uncommon > 5 years “Big bang” - most severe renal injury occurs with first infection
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Consequences of Reflux Nephropathy
Hypertension Most common cause of severe hypertension in children and young adults Renal scarring leads to ischemia and elevated renin Hypertension is related to degree of VUR and severity of scarring More profound with bilateral involvement Resolution of VUR does not reverse predisposition to hypertension if scarring is present
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Consequences of Reflux
Renal Growth infection is the most likely cause of altered growth reimplantation can accelerate growth - not to normal size Renal Failure Uncommon due to VUR alone < 1% Implications of recurrent pyelonephritis 15-25% of children with ESRD in earlier studies currently accounts for 2% ESRD cases Somatic Growth Children with VUR are small for age Surgical correction of VUR and medically-controlled VUR can positively affect growth
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Associated Anomalies UPJ Obstruction 5-25% will have VUR
0.8%-14% of VUR patients also have UPJ Can not base management on VCUG alone (obstructed renal pelvis can cause over-grading of VUR) High grade VUR can kink the ureter leading to UPJ When renal scan shows obstruction, pyeloplasty rather than reimplantation Correcting reflux risks amplifying obstruction - edema Improve outflow may increase VUR resolution Re-implantation may be necessary later
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Associated Anomalies Ureteral Duplication
VUR is the most common abnormality associated with complete ureteral duplication VUR is increased with duplication Resolution of VUR appears to be the same as single systems VUR more often in the lower pole ureter Weigert-Meyer rule Lateral and superior position with short submucosal tunnel
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Associated Anomalies Bladder Diverticulum
Lateral and cephalad to the orifice Disrupts UVJ anatomy - VUR Small diverticulum Resolution similar to primary VUR Large diverticulum Less likely to resolve
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Pregnancy and Reflux Pregnancy causes decreased bladder tone and physiologic dilation of upper tracts with increased urine volume and decreased flow. Predisposes to bacteruria with propensity for pyelonephritis In women with h/o reflux, increased risk of infection-related complications Increased risk for HTN With renal scarring, increased risk of preeclampsia
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Spontaneous Resolution
Age- and VUR grade- dependent Elongation of submucosal tunnel Bladder and ureteral growth Change of bladder dynamics Larger capacity Lower intravesical pressure
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Spontaneous Resolution
Low Grade Grade I: 82% at 5 years Grade II:80% at 5 years Intermediate Grade – III: 50% at 5 yrs Grade IV: 25% at 5 yrs Grade V 12% resolution Grade III & IV management presents the most controversy
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Spontaneous Resolution
Age at diagnosis Younger children are more likely to have VUR VUR is more likely to resolve in younger children Intervals of significant growth and beneficial urodynamic change are most likely to effect change Resolution usually occurs within the first few years after diagnosis Rarely resolves if continued reflux after 5 years
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Management Decision Making
Spontaneous resolution of VUR occurs in many infants and children - rarely at puberty More severe grades are less likely to resolve Sterile reflux does not appear to cause significant nephropathy Extended courses of prophylactic antibiotics are well tolerated by children Anti-Reflux surgery is highly successful in capable hands 95-99% success rate
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Management Decision Making
Medical management initially recommended for prepubertal children with I, II, III This also may be true for Grade IV - esp. in younger children with unilateral disease If no trend in improvement is seen in years, surgery is recommended Grade V is unlikely to resolve and surgery is recommended after infancy Observation may be reasonable if diagnosed perinatally
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Management Decision Making
Surgery recommended in most girls with persistent VUR Implications for future pregnancies Especially if recurrent infections or scars present Some discontinue antibiotics at puberty in girls Surgery if UTI occurs Prophylaxis can be stopped at puberty in boys Less likely to develop UTIs
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Medical Management Amoxicillin/Ampicillin Bactrim Macrodantin
Birth - 6 wks Bactrim >6 wks Biliary system matured Macrodantin > 2 months Minimizes fecal resistance Intermittent treatment not effective
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Medical Management Treat dysfunctional voiding
timed voids/double voids constipation Yearly Radiologic Studies U/S and Nuclear Cystography D/C prophylaxis when Cystography shows no VUR Complete reevaluation if develop pyelonephritis
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Surgical Management: Indications for Surgery
Breakthrough UTIs on prophylactic antibiotics Noncompliance with medical management Severe VUR (Grade IV & V), especially with pyelonephrotic changes (evidence of scarring) Failure of renal growth, new renal scars, or deterioration of renal function on serial studies Persistent VUR in girls at puberty Reflux associated with congenital abnormalities at the UVJ (e.g. bladder diverticulum)
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Surgical Management Decreases the incidence of pyelonephritis
50% to 10% UTI’s may persist Bacteriuria in 40% of post-op patients
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Surgical Management Creates valvular mechanism
Ureteral compression with bladder filling and contraction Sufficient length and muscular backing 5:1 length to diameter
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Surgical Management Techniques--infravesical Leadbetter-Politano Cohen
Supra hiatal Intravesical % success rate Cohen Cross-trigonal Useful for correcting VUR in thickened small or neuropathic bladder Procedure of choice with BN reconstruction % success rate Downside is difficulty with catheterizing UO’s Glenn-Anderson: infrahiatal, intravesical; % success Gil-Vernet: infrahiatal; 94% success
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Cohen Cross-trigonal Technique
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Cohen Cross-trigonal Technique: Bilateral Reimplantation
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Glenn-Anderson technique
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Gil-Vernet Technique
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Surgical Management Lich-Gregoir Extravesical 90 - 98% success rate
Advantages are Does not involve urinary contamination Less chance of bladder spasm/hematuria Less invasive, shorter hospital stay Disadvantages include potential for damage to nerves, leading to urinary retention in 4-36% of cases
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Lich-Gregoir Extravesical Technique
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Endoscopic Management
Deflux (Detranomer microspheres with sodium hyaluronan, a polysaccharide) 62-88% success for Grade III and IV reflux, respectively in short term follow-up2 Silicone Microimplants Migration and safety concerns exist Teflon Not widely used due to concerns regarding local and distant migration Collagen Not approved in the US 2 Stenberg and Lackgren. J. Urol, 1995, 154:
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Laparoscopic Management
Advantages Smaller Incisions Less Discomfort Brief Hospitalization Quicker convalescence Disadvantages Learning curve Intraperitoneal vs. extraperitoneal Instrumentation limited for pediatric use Increased operative time Increased cost with length of procedure and disposable equipment
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Post-Operative Care & Evaluation
Renal U/S 6 weeks VCUG 3-6 months Periodic F/U 18 months, 3 years, 5 years check U/A, BP, U/S
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Early Complications Reflux Obstruction
Contralateral or ipsilateral ureter Trigonal edema, bladder dysfunction Majority are low grade Obstruction Edema, spasms, blood clots Most are mild Occur 1-2 weeks post-op - pain, N/V, rarely fever Renal scan shows delay in excretion Nephrostomy tubes or ureteral stents if symptoms persist
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Late Complications Reflux Obstruction Short length to diameter ratio
Weak muscular backing Failure to treat secondary causes of VUR CIC and anticholinergics Treatment of dysfunctional voiding Obstruction Complete obstruction Ischemia or hiatal angulation Intermittent obstruction Lateral placement of orifice obstructs with filling
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Reflux: Conclusions Common
Indications for correction continue to change Natural history of VUR changing with perinatal diagnosis High resolution rate, medical management Surgical interventions highly successful New methods of surgical treatment evolving
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