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).

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.

There are two distinct presentations of VUR:

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:

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:

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).

The most devastating complication of VUR nephropathy is renal failure.

Vesicoureteral reflux can be primary or secondary.

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

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).

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.

Vesicoureteral reflux (VUR) may be associated with:

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.

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:

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.

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:

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:

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:

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.

VUR is classified into two types:

VUR is also classified into five grades:

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

This is attributed to several factors including:

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

VUR is divided into two types based on etiology:

Primary VUR:

Secondary VUR:

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:

Clinical signs and symptoms associated with a febrile UTI in a neonate may include: