8.1Introduction

•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.

Fig. 8.1 A micturating cystourethrogram showing sever bilateral vesicoureteral reflux

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

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).

•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 endstage renal failure in children.

•50 % are transient and resolve spontaneously.

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

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

8.2Pathophysiology

•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.

•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.

•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)

8.3Classification of VUR

•VUR is classified into two types:

–Primary VUR:

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

•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).

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)

–Neurogenic bladder

–Urethral stricture (Figs. 8.16 and 8.17)

–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)

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

Fig. 8.20 A micturating cystourethrogram showing grade I VUR

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

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