Vesicoureteral Reflux (VUR) in Children




(1)
Pediatric Surgery, AlSadik Hospital, Qatif, Saudi Arabia

 




8.1 Introduction






  • Normally urine travels antegrade in one direction from the kidneys to the bladder via the ureters to the urinary bladder.


  • Backward or retrograde flow of urine from the urinary bladder to the ureters or kidneys is prevented by a one way valve at the ureterovesical junction.


  • The valve is formed by the oblique entrance of the distal ureter through the wall of the bladder. This creates a tunnel of about 1–2 cm into the wall of the urinary bladder.


  • This tunnel is compressed as the bladder fills preventing backflow of urine.


  • Vesicoureteral reflux (VUR) is a retrograde flow of urine from the bladder into the ureters/kidneys (Fig. 8.1).

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    Fig. 8.1
    A micturating cystourethrogram showing sever bilateral vesicoureteral reflux


  • VUR occurs if the submucosal ureteric tunnel is short making the valve defective.


  • VUR is one of the common conditions in infants and children.


  • It has been estimated that 10 % of the population have some degree of VUR.


  • VUR is more common among younger children because of the relative shortness of the submucosal ureteric tunnel.


  • This susceptibility decreases as the child grows. This is as a result of growth and increase in the length of the ureteric tunnel.


  • It has been estimated that in children under the age of 1 year with a urinary tract infection, 70 % of them will have VUR.


  • This frequency decreases to 15 % by the age of 12 years.


  • VUR is more commonly diagnosed in males antenatally, but in later life there is a definite female preponderance with 85 % of VUR cases being diagnosed in females.


  • Overall prevalence of vesicoureteral reflux is unknown because many children are asymptomatic.


  • A frequency of 1–2 % of VUR was reported among healthy children.


  • The prevalence of VUR is higher among children with UTIs ranging from 15 to 70 %, depending on age.


  • Approximately one third of patients diagnosed prenatally with hydronephrosis on ultrasonography, were found postnatally to have VUR.


  • The incidence of reflux clearly is influenced by genetic factors, although the specific modes of inheritance is not defined.



    • Siblings of children with vesicoureteral reflux have a 25–33 % risk of also having VUR.


    • Offspring of parents with VUR have a 66 % risk of also having VUR.


    • This is higher in female offspring than male offspring.


  • There are two distinct presentations of VUR:



    • Hydronephrosis, often prenatally identified using ultrasonography.


    • Clinical urinary tract infection.


  • VUR can occur at any age but the average age at diagnosis of VUR is 2–3 years.


  • It was suggested that early diagnosis of children with VUR may prevent episodes of UTI and renal scarring.


  • Others feel that screening asymptomatic children will result in overtreatment of clinically insignificant VUR.


  • VUR is more common in white children than in those of other races.


  • VUR is less common in black children.


  • VUR is ten times as common in white children as in black children.


  • UTIs are known to be more common in girls than boys.


  • Among all children with UTIs, boys are more likely to have vesicoureteral reflux than girls (29 % of males vs 14 % of females).


  • Boys also tend to have higher grades of vesicoureteral reflux diagnosed at younger ages.


  • Vesicoureteral reflux is more likely to spontaneously resolve in boys when compared to girls.


  • VUR is more common among infants and progressively resolves in a substantial proportion of children.


  • The prevalence of VUR decreases as children age.


  • It was estimated that among patients who presented with UTI:



    • The prevalence of VUR was 70 % in patients younger than 1 year


    • The prevalence of VUR was 25 % in patients aged 4 years


    • The prevalence of VUR was 15 % in those aged 12 years


    • The prevalence of VUR was 5.2 % in adult patients.


  • VUR is more prevalent in male newborns, but VUR seems to be five to six times more common in females older than 1 year than in males.


  • The incidence decreases as patient age increases.


  • Approximately three-quarters of children being treated for reflux are girls.


  • The diagnosis of VUR depends on clinical suspicion and radiological investigations. The indications for radiological evaluation after the first attack of urinary tract infection include:



    • All children younger than 5 years.


    • Children of any age with febrile urinary tract infection.


    • Boys of any age with urinary tract infection.


  • In patients with VUR, there is a close correlation between the frequency of urinary tract infection and the severity of VUR nephropathy.


  • VUR nephropathy is considered the most common cause of childhood hypertension which is caused by increased renin secretion as a result of renal scarring (Figs. 8.2, 8.3, 8.4, and 8.5).

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    Figs. 8.2 and 8.3
    Abdominal ultrasound showing atrophic left kidney secondary to VUR


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    Figs. 8.4 and 8.5
    Clinical photographs showing hydroureters and dysplastic atrophic kidneys secondary to VUR


  • The most devastating complication of VUR nephropathy is renal failure.


  • Vesicoureteral reflux can be primary or secondary.



    • Primary vesicoureteral reflux results from a defect in the “flap valve” effect that normally prevents urine from flowing backward from the bladder into the ureters.


    • Secondary vesicoureteral reflux results from defective micturation secondary to obstruction in the urethra such as posterior urethral valve or stricture or neurogenic bladder.


  • More than 50 % of boys with posterior urethral valves have VUR. This can be unilateral or bilateral (Figs. 8.6 and 8.7).

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    Figs. 8.6 and 8.7
    Micturating cystourethrograms showing posterior urethral valve and VUR. Note the dilated posterior urethra


  • Dysfunctional voiding, with its inherent increase in intravesical pressure also results in VUR, even in otherwise healthy children.


  • The incidence of VUR is much higher in children with febrile UTIs (i.e., 30–70 %).


  • The incidence of prenatally diagnosed hydronephrosis caused by VUR ranges from 17 % to 37 % in the pediatric population.


  • Approximately 20–30 % of children with VUR present with renal lesions (Fig. 8.8).

    A429541_1_En_8_Fig5_HTML.gif


    Fig. 8.8
    A clinical intraoperative photograph showing a duplex system with hydroureter secondary to VUR and dysplastic kidney


  • The incidence of VUR in children and young adults with end-stage renal failure that necessitates dialysis or transplantation is about 6 %.


  • VUR is the fifth-most-common cause of end-stage renal failure in children.


Hydronephrosis Diagnosed Prenatally





  • 50 % are transient and resolve spontaneously.


  • 15 % have hydronephrosis that persists but is not associated with urinary tract obstruction (non-refluxing, non-obstructive hydronephrosis).


  • 35 % have a definite pathological cause for hydronephrosis. These include:



    • Pelvi-ureteric junction obstruction (11 %)


    • Vesicoureteral reflux (9 %)


    • Mega ureter (4 %)


    • Multicystic dysplastic kidney (2 %)


    • Ureterocele (2 %)


    • Posterior urethral valves (1 %)





  • Vesicoureteral reflux (VUR) may be associated with:



    • Urinary tract infection (UTI)


    • Hydronephrosis


    • Abnormal kidney development (renal dysplasia)


    • Increased risk for pyelonephritis, hypertension, and progressive renal failure.


  • VUR with concomitant UTI if not recognized and treated may lead to long-term effects on renal function and overall patient health.


  • The severity of VUR greatly varies and thus may affect patients differently. Some individuals have a genetic predisposition to renal injury.


  • Early diagnosis and vigilant monitoring of VUR are the cornerstones of management.


8.2 Pathophysiology






  • Anatomically, the ureter enters the urinary bladder through a hiatus in the detrusor muscle.


  • The ureter is composed of three muscle layers: inner longitudinal, middle circular, and outer longitudinal.


  • The outer longitudinal layer is enveloped by ureteral adventitia.


  • The inner longitudinal layer of smooth muscle passes through the ureteral hiatus, continues distally beyond the ureteral orifice into the trigone, and intertwines with the smooth muscle fibers of the contralateral ureter, forming the Bell muscle of the trigone and posterior urethra.


  • The middle circular muscle fibers, outer longitudinal muscle fibers, and periureteral adventitia merge with the bladder wall in the upper part of the ureteral hiatus to form the Waldeyer sheath.


  • This sheath attaches the extravesical portion of the ureter to the ureteral hiatus.


  • The normal valve mechanism of the ureterovesical junction includes:



    • Oblique insertion of the intramural ureter


    • Adequate length of the intramural portion of the ureter


    • Strong detrusor support.


  • The distal ureter then passes obliquely through a submucosal tunnel before opening into the bladder lumen via the ureteral orifice.


  • This creates a tunnel of about 1–2 cm long into the wall of the urinary bladder.


  • This tunnel is compressed as the bladder fills and the intravesical pressure increases preventing backflow of urine from the urinary bladder to the upper urinary tract.


  • The length of this submucosal tunnel and the muscular coat is important in creating a one-way valve preventing backflow of urine.


  • If the length of the submucosal tunnel is short or if the muscular backing is inadequate, the one-way valve mechanism becomes incompetent, resulting in reflux.


  • It was found that the ratio of tunnel length to ureteral diameter is important in the one-way mechanism.


  • A ratio of at least 5:1 is important to ensure a competent one-way valve to prevent reflux.


  • An abnormal short intramural tunnel results in a malfunctioning flap-valve mechanism and urine tends to reflux up the ureter and into the collecting system (VUR).


  • It was estimated that refluxing ureters have an intramural tunnel length–to–ureteral diameter ratio of 1.4:1.


  • When this protective mechanism fails, VUR occurs.


  • VUR will lead to ascending infection and pyelonephritis which are the essential causes of reflux nephropathy.

    A429541_1_En_8_Figa_HTML.gif


  • A close correlation was established between the frequency of UTI and severity of reflux nephropathy in patients with vesicoureteral reflux.


  • Renal scarring may result from a single episode of pyelonephritis, especially in very young patients.


  • Most renal scarring tends to occur at the renal poles, where the anatomy of the renal papillae permits backflow of urine into the collecting ducts.


  • This phenomenon is referred to as intrarenal reflux and gives pathogenic bacteria access to the renal tubules.


  • The human kidney contains two types of renal papillae:



    • Simple (convex) papilla


    • Compound (concave) papilla


  • Compound papillae are commonly seen at the polar regions of the kidney, whereas simple papillae are located at nonpolar regions of the kidney.


  • Approximately 66 % of human papillae are simple (convex) and 33 % are compound (concave).


  • Intrarenal reflux or retrograde movement of urine from the renal pelvis into the renal parenchyma is a function of intrarenal papilla.


  • Simple papillae possess oblique, slit like, ductal orifices that close upon increased intrarenal pressure and do not allow intrarenal reflux.


  • Compound papillae possess gaping orifices that are perpendicular to the papillary surface that remain open upon increased intrarenal pressure allowing free intrarenal reflux.


  • Renal scars are often present at initial diagnosis of VUR and usually develop during the first years of life.


  • Persistent intrarenal reflux causes renal scarring and eventual reflux nephropathy.


  • Reflux nephropathy leads to:



    • Impaired renal function


    • Hypertension


    • Proteinuria


    • End stage renal disease


  • These effects depend on the type of urine.


  • Two types of urine may reflux and enter the renal papillae: infected urine or sterile urine.


  • Intrarenal reflux of infected urine is primarily responsible for the renal damage.


  • The presence of bacterial endotoxins (lipopolysaccharides) activates the host’s immune response and a release of oxygen free radicals. The release of oxygen free radicals and proteolytic enzymes results in fibrosis and scarring of the affected renal parenchyma during the healing phase.


  • This initial scar formation at the infected polar region distorts the neighboring papillae and converts simple papillae into compound papillae.


  • Compound papillae, in turn, perpetuate further intrarenal reflux which further increases renal scarring.


  • Compound papillae are most commonly found at the renal poles, where renal scarring is most commonly observed.


  • These focal areas of renal scars can be detected by Renal scan (DMSA).


  • Diffuse lesions on renal scan are believed to be due to renal dysplasia, which results from abnormal kidney development.


  • It is observed in patients who have higher grades of reflux (IV and V) and who have never had any evidence of UTI or pyelonephritis.


  • Intrarenal reflux of sterile urine (under normal intrapelvic pressures) has not been shown to produce clinically significant renal scars.


  • Treatment with long-term low-dose antibiotic prophylaxis to maintain sterile urine appears to inhibit renal scarring in children with uncomplicated VUR.


  • Thus, renal scars appear to develop only in the presence of intrarenal reflux of infected urine.


  • One exception to this is intrarenal reflux of sterile urine in the presence of abnormally high intravesical pressures.


  • Abnormally high intravesical pressure is seen in:



    • Bladder outlet obstruction (functional or anatomical)


    • Nonneurogenic neurogenic bladder, or Hinman syndrome


    • Gastrointestinal dysfunction including chronic constipation


    • Children with overactive bladder (e.g. detrusor hyperreflexia, detrusor instability)


  • Renal lesions are associated with higher grades of reflux.


  • Renal units with low-grade reflux may grow normally, but high grades of reflux are associated with renal growth retardation.


  • Pyelonephritic scarring may, over time, cause serious hypertension due to activation of the renin-angiotensin system.


  • Scarring related to VUR is one of the most common causes of childhood hypertension.


  • It was estimated that hypertension develops in 10 % of children with unilateral scars and in 18.5 % with bilateral scars.


  • Approximately 4 % of children with VUR progress to end-stage renal failure.


8.3 Classification of VUR






  • VUR is classified into two types:



    • Primary VUR:



      • This is the most common type of VUR (Figs. 8.9 and 8.10).

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        Figs. 8.9 and 8.10
        Micturating cystourethrogram showing severe VUR. Note the dilated tortous ureters


      • It is caused by a defect in the development of the valve-like effect at the uretrovesical junction with insufficient submucosal ureteric length relative to its diameter.


      • This type is usually detected antenataly or shortly after birth.


      • Primary reflux is vesicoureteral reflux in an otherwise normally functioning lower urinary tract.


      • This is precipitated by a congenital defect.


      • Lack of longitudinal muscle of the intravesical ureter result in anomaly of the ureterovesicular junction (UVJ).


      • This defect causes inadequacy of the valvular mechanism and failure of its function as a one-way valve leading to backflow of urine from the urinary bladder to the ureters and kidneys.


      • This defect can be unilateral or bilateral (Fig. 8.11)

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        Fig. 8.11
        A micturating cystourethrogram showing bilateral VUR


    • Secondary VUR:



      • Secondary reflux is vesicoureteral reflux that is associated with or caused by an obstructed or poorly functioning lower urinary tract.


      • In this category the valvular mechanism is intact and healthy to start with but becomes overwhelmed by raised intravesicular pressures associated with obstruction.


      • This leads to distortion of the ureterovesical junction and failure of its function as a one-way valve.


      • Secondary VUR can be further divided into anatomical and functional groups.


      • This is seen in those with posterior urethral valves (anatomical) or a neurogenic bladder (functional).


      • The main causes of secondary VUR are:



        • Posterior urethral valves (Figs. 8.12, 8.13, 8.14, and 8.15)

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          Figs. 8.12 and 8.13
          Micturating cystourethrograms showing posterior urethral valve and associated secondary VUR. Note the dilated posterior urethra and the diverticulae from the urinary bladder


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          Figs. 8.14 and 8.15
          Micturating cystourethrograms showing posterior urethral valve without VUR


        • Neurogenic bladder


        • Urethral stricture (Figs. 8.16 and 8.17)

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          Figs. 8.16 and 8.17
          Micturating cystourethrogram showing urethral stricture secondary to hypospadias repair and secondary mild VUR


        • Meatal stenosis


  • VUR is also classified into five grades:



    • Voiding cystourethrography (VCUG) is the criterion standard in diagnosis of VUR, providing precise anatomic detail and allows grading of the reflux.


    • The International Classification System for VUR is based on the radiographic appearance of the ureter, renal pelvis and calyces on a voiding cystogram.


    • It is important to note that the presence of a severe reflux on one side may hide a milder degree of reflux on the other side in those with bilateral reflux.


    • In these cases reflux on the milder side may appear postoperatively following treatment of the more severely affected side.


    • This is one of the causes of appearance of reflux on the contralateral side following successful treatment of the severely affected side.


    • The International Classification System for VUR is as follows:



      • Grade I – Reflux into nondilated ureter (Figs. 8.18, 8.19, and 8.20)

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        Figs. 8.18 and 8.19
        Diagrammatic representation of grade I VUR. The blue color represents urine in the ureter


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        Fig. 8.20
        A micturating cystourethrogram showing grade I VUR


      • Grade II – Reflux into renal pelvis and calyces without dilation (Figs. 8.21 and 8.22)

        A429541_1_En_8_Fig13_HTML.gif


        Figs. 8.21 and 8.22
        Diagrammatic representation of grade II VUR and a micturating cystourethrogram showing grade II VUR


      • Grade III – Reflux with mild to moderate dilation and minimal blunting of fornices (Figs. 8.23, 8.24, and 8.25)

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        Fig. 8.23
        A micturating cystourethrogram showing grade III VUR


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        Figs. 8.24 and 8.25
        Diagrammatic representation of grade III VUR and a micturating cystourethrogram showing grade III VUR. Note the hydronephrotic pelvic right kidney


      • Grade IV – Reflux with moderate ureteral tortuosity and dilation of pelvis and calyces (Figs. 8.26, 8.27, and 8.28)

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        Figs. 8.26, 8.27, and 8.28
        Diagrammatic representation of grade IV VUR and Micturating cystourethrograms showing grade IV VUR


      • Grade V – Reflux with gross dilation of ureter, pelvis, and calyces, loss of papillary impressions, and ureteral tortuosity (Figs. 8.29, 8.30, and 8.31)

        A429541_1_En_8_Fig17_HTML.gif


        Fig. 8.29
        Diagrammatic representation of grade V VUR


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        Figs. 8.30 and 8.31
        A micturating cystourethrogram showing grade V VUR. Note the dilated tortuous ureters


8.4 Etiology of VUR






  • VUR is prevented by a one way valve like effect at the uretero-vesical junction.


  • This is attributed to several factors including:



    • The oblique entrance of the ureter into the urinary bladder


    • The submucosal tunnel through which the ureter enter into the urinary bladder


    • The ureter’s muscular attachments


  • Failure of this mechanism will result in retrograde flow of urine.


  • VUR is divided into two types based on etiology:



    • Primary VUR


    • Secondary VUR


  • Primary VUR:



    • Primary VUR is the most common form of reflux


    • It is due to incompetent or inadequate ureterovesical junction (UVJ)


    • The exact cause of the defect in primary VUR is unknown


    • This may be secondary to an abnormally short intravesical ureteric segment or abnormal surrounding muscles.


    • Other factors that contribute to the etiology of primary VUR include:



      • The existence of a strong genetic component is supported by the high rate of reflux in relatives of patients with reflux, but the mechanism of transmission is not clear.


      • The possibility of urinary tract infection as a cause of VUR is not clear and many think that UTI and VUR are independent variables. Urinary tract infections may cause reflux due to the elevated pressures associated with inflammation.


  • Secondary VUR:



    • Secondary VUR is reflux that is associated with or caused by an obstructed or poorly functioning lower urinary tract.


    • This is seen in children with congenital bladder outlet obstruction and neurogenic bladder (Figs. 8.32 and 8.33).

      A429541_1_En_8_Fig19_HTML.gif


      Figs. 8.32 and 8.33
      Micturating cystourethrograms showing neurogenic bladder with VUR


    • More than 50 % of boys with posterior urethral valves have vesicoureteral reflux (Figs. 8.34 and 8.35).

      A429541_1_En_8_Fig20_HTML.gif


      Figs. 8.34 and 8.35
      Micturating cystourethrograms showing posterior urethral valve and severe right vesicoureteral reflux. Note the dilated posterior urethra


    • In these patients, VUR can be unilateral or bilateral


    • Other causes include urethral or meatal stenosis


    • Bladder instability, neurogenic bladder and non-neurogenic bladder


    • Dysfunctional voiding, with its inherent increase in intravesical pressure, is a cause reflux, even in otherwise healthy children.


    • The combination of high-pressure voiding and vesicoureteral reflux increases the risk of pyelonephritis beyond that of the child with low-pressure reflux.


    • A unique group of children presents with dysfunctional elimination, which consists of a symptom complex heralded by infection, severe constipation, and daytime wetting (Figs. 8.36, 8.37, and 8.38).

      A429541_1_En_8_Fig21_HTML.gif


      Figs. 8.36, 8.37, and 8.38
      Plain abdominal radiograph and micturating cystourethrogram showing bowel dysfunction with chronic constipation and VUR


    • Some of these children have infrequent voiding and incomplete bladder emptying, which further increases the likelihood of UTI.


    • Hardikar syndrome: This include:



      • Vesicoureteral reflux


      • Hydronephrosis


      • Cleft lip and palate


      • Intestinal obstruction and other symptoms


8.5 Clinical Features






  • VUR cannot be diagnosed prenatally.


  • VUR however may be suspected in the prenatal period, when transient dilatation of the upper urinary tract is noted in conjunction with bladder emptying.


  • Approximately 10 % of neonates diagnosed prenatally with dilatation of the upper urinary tract will be found to have VUR postnatally.


  • In general, VUR is almost always asymptomatic.


  • VUR does not cause any specific signs or symptoms unless complicated by UTI (febrile UTI).


  • Most infants and children with vesicoureteral reflux (VUR) present in one of two distinct groups:



    • The first group presents with hydronephrosis, often prenatally identified using ultrasonography.


    • The second group presents with urinary tract infection (UTI).


Etiology of VUR





  • Primary causes of VUR:



    • Short or absent intravesical ureter


    • Absence of adequate detrusor backing


    • Lateral displacement of the ureteral orifice


    • Paraureteral (Hutch) diverticulum


  • Secondary causes of VUR:



    • Cystitis or UTI


    • Bladder outlet obstruction (Posterior urethral valve, urethral stricture, meatal stenosis)


    • Neurogenic bladder


    • Detrusor instability

Jul 10, 2017 | Posted by in UROLOGY | Comments Off on Vesicoureteral Reflux (VUR) in Children
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