Vesicoureteral Reflux

Updated: Nov 21, 2015
  • Author: Carlos Roberto Estrada, Jr, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Vesicoureteral reflux (VUR) is characterized by the retrograde flow of urine from the bladder to the kidneys. VUR may be associated with urinary tract infection (UTI), hydronephrosis, and abnormal kidney development (renal dysplasia). The relation of these conditions to VUR is discussed in this article.

Unrecognized VUR with concomitant UTI may lead to long-term effects on renal function and overall patient health. Some individuals with VUR are at an increased risk for pyelonephritis, hypertension, and progressive renal failure. However, the severity of VUR greatly varies and thus may affect patients differently. Some individuals have a genetic predisposition to renal injury. Evaluation of VUR treatment outcomes should consider not only resolution of reflux over time but also resolution of UTIs and the overall health of the kidneys.

The evaluation and management of VUR in children is currently undergoing re-evaluation, as guidelines for treatment are being rewritten. (For additional information on pediatric vesicoureteral reflux, see the Medscape Reference article Pediatric Vesicoureteral Reflux.)

Early diagnosis and vigilant monitoring of VUR are the cornerstones of management. Voiding cystourethrography (VCUG) or radionuclear cystourethrography (RNC) is used to confirm the diagnosis of VUR. A dimercaptosuccinic acid (DMSA) renal scan is used to evaluate for any renal abnormalities. Until the reflux resolves or the reflux is surgically treated, the patient should undergo monitoring with cystography (RNC or VCUG) every 12-24 months. Serial ultrasonography can also be performed to evaluate renal growth, especially in patients with a history of renal abnormalities such as size discrepancy or hydronephrosis. Prophylactic antibiotics are prescribed to reduce the risk of bacterial infection of the bladder while reflux is present. Bladder management to ensure good lower urinary tract hygiene should be considered in children who have undergone toilet training.


History of the Procedure

Galen and Asclepiades described the valve action of the ureterovesical junction as early as the second century CE. In 1903, Sampson and Young described the functional flap-valve mechanism at the level of the ureterovesical junction, which is created by the oblique course of the ureter within the intramural portion of the bladder wall. In 1913, Legueu and Papin described a patient with hydronephrosis and hydroureter in whom urine was shown refluxing through a widely patent ureteral orifice.

In his report on cystography in 1914, Kretschmer demonstrated that 4 of the 11 children he studied had reflux. In 1929, Gruber noted that the incidence of VUR varied based on the length of the intravesical ureter and muscularity of the detrusor backing. Paquin reported that the tunnel length–to–ureteral diameter ratio should be approximately 5:1 to prevent reflux. In the mid-to-late 1950s, Hutch postulated the causal relationship between VUR and chronic pyelonephritis in a cohort of patients with spinal cord injury, and, in 1959, Hodson demonstrated that renal parenchymal scarring is more common in children with VUR and UTIs.

Ransley and Ridson confirmed the studies of Tanagho in 1975 by showing that reflux could be experimentally created in animals by modifying the ureterovesical junction; in subsequent studies, they were able to show the correlation between reflux, renal papilla anatomy, pyelonephritis, and renal injury. At the same time, Smellie and Normand performed long-term studies of patients with reflux; they documented the natural history of patients treated medically. [1]

At the same time, Paquin, Hutch, Lich and Gregoire, Daines and Hudson, Politano and Leadbetter, Glenn and Anderson, and Cohen developed and popularized various surgical techniques for treating VUR. The International Reflux Grading System was adopted in the early 1980s, and the International Reflux Study compared medical approaches with surgical approaches to reflux. Finally, endoscopic treatment for reflux was introduced in the late 1980s. In recent years, Noe and colleagues showed a genetic predisposition for reflux. In addition, the widespread use of antenatal ultrasonography has allowed identification of fetuses with urinary tract abnormalities, which can result in diagnosis of reflux prior to the development of UTIs.



VUR is defined as retrograde regurgitation of urine from the urinary bladder up the ureter and into the collecting system of the kidneys. The International Reflux Grading system classifies VUR into 5 grades, depending on the degree of retrograde filling and dilatation of the renal collecting system. This system is based on the radiographic appearance of the renal pelvis and calyces on a voiding cystogram, as follows:

  • Grade I: Urine backs up into the ureter only, and the renal pelvis appears healthy, with sharp calyces.

  • Grade II: Urine backs up into the ureter, renal pelvis, and calyces. The renal pelvis appears healthy and has sharp calyces.

  • Grade III: Urine backs up into the ureter and collecting system. The ureter and pelvis appear mildly dilated, and the calyces are mildly blunted.

  • Grade IV: Urine backs up into the ureter and collecting system. The ureter and pelvis appear moderately dilated, and the calyces are moderately blunted.

  • Grade V: Urine backs up into the ureter and collecting system. The pelvis is severely dilated, the ureter appears tortuous, and the calyces are severely blunted.




Historically, epidemiologic studies using VCUG in presumably healthy neonates, infants, and children reported that the incidence of VUR is less than 1%. However, this figure is probably an underestimation because no large population studies have been performed to assess the true incidence of VUR; in addition, reflux is discovered in selected patients such as those who present with a prenatal or postnatal hydronephrosis or UTI or who have a family history of VUR.

VUR is 10 times as common in white children as in black children, and children with red hair are recognizably at an increased risk. VUR is more prevalent in male newborns, but VUR seems to be 5-6 times more common in females older than one year than in males. The incidence decreases as patient age increases.

The incidence of VUR is much higher in children with febrile UTIs (ie, 30-70%). Approximately 13,000 children younger than 17 years are hospitalized annually in the United States for the treatment of pyelonephritis. UTIs account for more than 1.1 million physician office visits among children younger than 18 years, and about 25,000 visits to urologists are for evaluation and treatment of VUR.

Today, the incidence of prenatally diagnosed hydronephrosis caused by VUR ranges from 17-37% in the pediatric population, and approximately 20-30% of children with VUR present with renal lesions. The incidence of VUR in children and young adults with end-stage renal failure (chronic renal insufficiency [CRI]) that necessitates therapy (dialysis or transplantation) is about 6%. VUR is the fifth-most-common cause of CRI in children. [2]

VUR has a definite genetic component, but the exact mode of inheritance remains unknown. Currently, researchers hypothesize that VUR is inherited dominantly with a variable penetrance. Up to 76% of index-case patients (ie, patients with reflux) develop VUR in utero, and up to 34% of patients with reflux have siblings who are also affected.



Primary causes of VUR include the following:

  • Short or absent intravesical ureter

  • Absence of adequate detrusor backing

  • Lateral displacement of the ureteral orifice

  • Paraureteral (Hutch) diverticulum

Secondary causes of VUR include the following:

  • Cystitis or UTI

  • Bladder outlet obstruction

  • Neurogenic bladder

  • Detrusor instability



When the ureter inserts into the trigone, the distal end of the ureter courses through the intramural portion of the bladder wall at an oblique angle. The intramural tunnel length–to–ureteral diameter ratio is 5:1 for a healthy nonrefluxing ureter. As the bladder fills with urine and the bladder wall distends and thins, the intramural portion of the ureter also stretches, thins out, and becomes compressed against the detrusor backing. This process allows a continual antegrade flow of urine from the ureter into the bladder but prevents retrograde transmission of urine from the bladder back up to the kidney; thus, a healthy intramural tunnel, within the bladder wall, functions as a flap-valve mechanism for the intramural ureter and prevents urinary reflux.

An abnormal intramural tunnel (ie, short tunnel) results in a malfunctioning flap-valve mechanism and VUR. When the intramural tunnel length is short, urine tends to reflux up the ureter and into the collecting system. Pacquin reports that refluxing ureters have an intramural tunnel length–to–ureteral diameter ratio of 1.4:1. To prevent reflux during ureteral reimplantation, the physician must obtain a minimum tunnel length–to–ureteral diameter ratio of 3:1.

The human kidney contains two types of renal papillae: simple (convex) papilla and compound (concave) papilla. Compound papillae predominate at the polar regions of the kidney, whereas simple papillae are located at nonpolar regions. Approximately 66% of human papillae are convex and 33% are concave.

Intrarenal reflux or retrograde movement of urine from the renal pelvis into the renal parenchyma is a function of intrarenal papillary anatomy. Simple papillae possess oblique, slitlike, ductal orifices that close upon increased intrarenal pressure. Thus, simple papillae do not allow intrarenal reflux. However, compound papillae possess gaping orifices that are perpendicular to the papillary surface that remain open upon increased intrarenal pressure. These gaping orifices allow free intrarenal reflux.

Patients with uncorrected VUR may develop renal scarring and impaired renal growth. Renal scars are often present at initial diagnosis 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, and proteinuria.

Two types of urine may enter the renal papillae: infected urine or sterile urine. Intrarenal reflux of infected urine appears to be 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.

Initial scar formation at the infected polar region distorts local anatomy of the neighboring papillae and converts simple papillae into compound papillae. Compound papillae, in turn, perpetuate further intrarenal reflux and additional renal scarring. Thus, a potentially vicious cycle of events may occur after initial intrarenal introduction of infected urine. Compound papillae are most commonly found at the renal poles, where renal scarring is most commonly observed. Renal scan (DMSA) reveals these lesions focally. 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. As described by Yeung et al, these kidneys may have very low or no function in 5% of girls and 78% of boys. [3]

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 seems to inhibit renal scarring in children with uncomplicated VUR. [1, 4] Thus, renal lesions appear to develop only in the setting of intrarenal reflux in combination with UTI. One exception to this may include intrarenal reflux of sterile urine in the setting of abnormally high detrusor pressures.

Hodson et al completely obstructed the urethra of Sinclair miniature piglets and created an artificially high intravesical pressure that was transmitted to the renal pelvis. Intrarenal reflux of sterile urine in this highly pressurized system led to the formation of renal lesions. Apparently (at least in animal model studies), sterile reflux may also produce scarring but only with high intravesical pressures (eg, infravesical outlet obstruction or poorly compliant neurogenic bladder).

Renal lesions are associated with higher grades of reflux. 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. Wallace reports that hypertension develops in 10% of children with unilateral scars and in 18.5% with bilateral scars. Among adults with reflux nephropathy, 34% ultimately develop hypertension. Approximately 4% of children with VUR progress to end-stage renal failure. Renal units with low-grade reflux may grow normally, but high grades of reflux are associated with renal growth retardation.

Bladder outlet obstruction (functional or anatomical), learned voiding abnormalities (eg, nonneurogenic neurogenic bladder, or Hinman syndrome), and gastrointestinal dysfunction may cause VUR. Unphysiologically elevated intravesical pressures are common with all of these abnormalities. Children with overactive bladder (eg, detrusor hyperreflexia, detrusor instability) generate a high intravesical pressure, which can exacerbate pre-existing VUR or cause secondary VUR. These children empty their bladder relatively well, with minimal postvoid residual urine.

Acquired voiding dysfunction (eg, Hinman syndrome [nonneurogenic neurogenic bladder]) produces functional bladder outlet obstruction from voluntary contraction of the external sphincter during urination. These children generate high intravesical pressure, develop detrusor instability, and have high postvoid residual urine volumes. Encopresis and constipation are also common in this setting.



VUR 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 reflux postnatally. It should be noted that VUR cannot be diagnosed prenatally.

In general, VUR does not cause any specific signs or symptoms unless complicated by UTI. In other words, VUR is almost always asymptomatic unless it has led to a kidney infection (febrile UTI). Clinical signs and symptoms associated with a febrile UTI in a neonate may include irritability, persistent high fever, and listlessness. In cases of VUR and febrile UTI associated with a serious underlying urinary tract abnormality, the neonate could present with respiratory distress, failure to thrive, renal failure, flank masses, and urinary ascites.

Older children may more clearly communicate signs and symptoms associated with a UTI (eg, urgency, frequency, dysuria, incontinence), but, unless the UTI is associated with a fever, there is little reason to suspect VUR.



The goals of medical intervention in patients with vesicoureteral reflux (VUR) are to allow normal renal growth, to prevent UTI and pyelonephritis, and to prevent renal failure. Initiate medical management in prepubertal children with grades I-III reflux and most children with grade IV reflux.

Relative indications for surgical management of VUR include grades IV and V reflux, persistent reflux despite medical therapy (beyond 3 y), breakthrough UTIs in patient who are receiving antibiotic prophylaxis, lack of renal growth, multiple drug allergies that preclude the use of prophylaxis, a desire to terminate antibiotic prophylaxis (either by the physician or the patient/parents), and medical noncompliance. Absolute indications for surgical management include breakthrough pyelonephritis, progressive renal scarring in patients receiving antibiotic prophylaxis, and an associated ureterovesical junction abnormality.


Relevant Anatomy

The normal valve mechanism of the ureterovesical junction includes oblique insertion of the intramural ureter, adequate length of the intramural portion of the ureter, and strong detrusor support.

The ureter is composed of 3 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.



Ureteral reimplantation is contraindicated as a first-line therapy in patients with secondary vesicoureteral reflux (VUR), which may arise as an inappropriate increase in detrusor filling pressure.

Causes of secondary reflux include chronic bladder outlet obstruction, neurologic disorders (eg, myelomeningocele, spinal cord injury), and overactive bladder. All of these disease processes lead to poor bladder compliance; therefore, treating detrusor dysfunction before performing ureteral reimplantation is recommended. If the physician neglects the bladder and proceeds with ureteral implantation first, the risk of recurrent reflux is high, or, if the bladder wall is abnormally thickened, the risk of distal ureteral obstruction is greater after surgical treatment. Contraindications to surgery include detrusor instability or Hinman syndrome.