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Vesicoureteral Reflux

Reflux Vesico Ureteral

Vesicoureteral reflux (VUR) is a condition where the urine flow is retrograde in direction.


Presentation

VUR typically presents in childhood. The clinical features on presentation are:

If the upper urinary tract transiently dilates when the bladder is emptying, a diagnosis of VUR should be considered. Almost 10% neonates that have been diagnosed with dilatation of the upper urinary tract prenatally are likely to develop reflux. A diagnosis of VUR cannot be made in the prenatal period. VUR is usually asymptomatic and is detected when the patient develops a febrile UTI. 

Abdominal Tenderness
  • Fever, flank or abdominal tenderness, or an enlarged palpable kidney may be present. See Clinical Presentation for more detail. Diagnosis Diagnosis of UTI depends on obtaining accurate urine culture findings.[emedicine.com]
Fussiness
  • […] symptoms of a bladder infection or a UTI may be: urgency to urinate a burning sensation or pain when urinating blood in the urine cloudy urine urine with a strong, unpleasant smell dribbling urine, incontinence, and bed-wetting fever and abdominal pain fussiness[medicalnewstoday.com]
  • Infants may present with irritability, fussiness, poor oral intake, foul smelling urine in the diaper, or a fever. Lastly, VUR may be identified as part of a sibling or offspring screening work-up for VUR.[clinicaladvisor.com]
Lethargy
  • In infants, the signs and symptoms of a urinary tract infection may include only fever and lethargy, with poor appetite and sometimes foul-smelling urine, while older children typically present with discomfort or pain with urination and frequent urination[en.wikipedia.org]
  • […] children can be difficult, for the following reasons: Children often present with nonspecific signs and symptoms; infection in infants can manifest as failure to thrive, with or without fever; other features include vomiting, diarrhea, anorexia, and lethargy[emedicine.com]
  • UTIs generally cause the following symptoms: Urination problems — strong urges, burning sensation, frequent urges but small amounts Blood in urine Pain in the belly or sides Fever Vomiting, diarrhea Lethargy (lack of energy).[denverurology.com]
  • […] symptoms, if VUR is not treated, include: a palpable abdominal mass, caused by a swollen kidney poor weight gain hypertension, or high blood pressure kidney failure protein in the urine scarring of kidney tissue An infant may have vomiting, diarrhea, lethargy[medicalnewstoday.com]
Hyperreflexia
  • Children with overactive bladder (eg, detrusor hyperreflexia, detrusor instability) generate a high intravesical pressure, which can exacerbate pre-existing VUR or cause secondary VUR.[emedicine.com]
  • In children a high intravesical pressure may develop secondary to detrusor instability or detrusor hyperreflexia that may lead to secondary VUR or worsen the pre-existing VUR.[symptoma.com]
Hyperactivity
  • In some children, medication may be needed to decrease bladder hyperactivity.[wmuro.com]
Kidney Failure
  • Kidney failure. Scarring can cause a loss of function in the filtering part of the kidney. This may lead to kidney failure, which can occur quickly (acute kidney failure) or may develop over time (chronic kidney disease).[mayoclinic.org]
  • When not treated through either antibiotic therapy or, when necessary, surgery, VUR can allow bacteria that grow in urine to enter the kidneys, which can lead to kidney infection, kidney damage, and chronic kidney failure. Types.[urology.ucla.edu]
  • Other symptoms include flank pain and hypertension, uremia, and kidney failure in advanced cases of reflux nephropathy.[amboss.com]
  • Acute kidney failure can occur if toxins build up rapidly in the blood because of a loss of kidney function. In severe cases, the patient may need emergency dialysis. Chronic kidney disease happens when the kidneys' function progressively worsens.[medicalnewstoday.com]
  • As the child gets older, other symptoms, such as bedwetting, high blood pressure, protein in the urine, and kidney failure, may appear. Diagnosis Common tests to show the presence of a urinary tract infection include urine analysis and cultures.[uoflphysicians.com]
Dysuria
  • Children with VUR are usually asymptomatic until they develop a urinary tract infection ( fever, dysuria, urgency.). Other symptoms include flank pain and hypertension, uremia, and kidney failure in advanced cases of reflux nephropathy.[amboss.com]
  • Open surgical intervention is associated with the highest success rate (98-100%) but also the greatest morbidity (transient frequency, urgency, dysuria and hematuria).[clinicaladvisor.com]
  • The clinical features on presentation are: History of fetal hydronephrosis History of UTI Hypertension Clinical features of UTI: Fever, flank pain, abdominal pain, urgency, frequency, dysuria, hematuria Bed wetting If the upper urinary tract transiently[symptoma.com]
  • Children with UTI may have fever, abdominal or flank pain, dysuria, frequency, urgency, wetting accidents, or rarely hematuria.[merckmanuals.com]
  • Recommendation: If symptomatic breakthrough urinary tract infection occurs (manifest by fever, dysuria, frequency, failure to thrive, or poor feeding), a change in therapy is recommended.[auanet.org]
Penile Pain
  • “Standard: Symptoms indicative of BBD should be sought in the initial evaluation (including urinary frequency and urgency, prolonged voiding intervals, daytime wetting, perineal/penile pain, holding maneuvers [posturing to prevent wetting] and constipation[doi.org]
  • pain, holding maneuvers (posturing to prevent wetting), and constipation/encopresis.[auanet.org]

Workup

All neonates that have been diagnosed with hydronephrosis should undergo urine culture and urine analysis in order to rule out UTI. When analyzing the results from these tests, we should keep in mind that creatinine values from samples drawn within the first 24 hours of life will represent maternal creatinine values hence the creatinine level should be assessed after 24 hours of life. The normal serum creatinine in the neonatal period is 0.4 mg/dl. Serum electrolyte levels should also be measured to look for acidosis in all neonates diagnosed with hydronephrosis secondary to VUR as they may have developed a dysplastic kidney on the side with VUR. 

The radiological tests may include the following:

  • VCUG: Recommended by the American Academy of Pediatrics committee on quality improvement for all children 2 months to 2 years of age after first episode of a febrile UTI [18].
  • Urodynamic studies: For cases with VUR secondary to dysfunction of the lower urinary tract.
  • Renal ultrasonography: To determine the presence and the extent of hydronephrosis.
  • Nuclear renal scan using dimercaptosuccinic acid (DMSA): To confirm pyelonephritis, detect renal scarring and evaluate progress in treatment of VUR when using medical management.
  • Cystoscopy: Used when there is a suspicion of ureterocele and radiologic studies are unable to adequately define the urinary tract anatomy.

Usually, the patient first undergoes a renal ultrasound, which is then followed by a VCUG. Reflux diagnosed on a VCUG is graded as :

  • Mild: Grade I and II
  • Moderate: Grade III
  • Severe: Grade IV and V

Treatment

Mild to moderate VUR is known to resolve spontaneously over months to years. The treatment for cases with mild to moderate VUR is focused on preventing infections. They were previously recommended daily antibiotic prophylaxis but this has been discontinued in modern day practice. However, in children less than two years old with a grade II to grade V VUR and in all cases of severe VUR an antibiotic prophylaxis with either of the following is advised:

For children with grade I to grade IV VUR, the American Academy of Pediatrics does not recommend any antibiotic prophylaxis.

Severe VUR that is associated with elevated intravesical pressure and is primarily treated with anti-cholinergic medications such as oxybutynin and solifenacin. Alternative forms of treatment such as surgical bladder augmentation or use of botulinum toxin may be considered if there is insufficient or no response to the anti-cholinergic drugs. Behavioral modification therapy with or without biofeedback is recommended for cases with bladder and bowel dysfunction.

Patients with symptoms such as renal scarring, impairment of renal growth and recurrent infections may be considered for ureteral re-implantation or endoscopic hyaluronic acid/dextranomer injection.

The definitive indications for surgical correction of VUR include:

  • Non-compliance of medical management
  • Grade V VUR in older children
  • Febrile UTI

The relative indications for surgical correction of VUR include:

  • Stable moderate VUR that persists into the peripubertal age.

Prognosis

Ureteral implantation has a high success rate of >95% if performed by an experienced surgeon. The incidence of pyelonephritis decreases considerably after the procedure but the incidence of renal scarring and cystitis tend to remain the same as compared to medical management for these conditions in cases with VUR. 

An alternative to surgical or medical management is endoscopic repair of VUR. However, it has a lower success rate as compared to open surgical repair. Males less than 5 years of age, especially those less than 1 year old, with a grade I-III reflux have a high chance for a spontaneous resolution of VUR. The higher grades of reflux (IV-V) may also resolve spontaneously if the patient does not develop an infection. The likelihood of a spontaneous resolution of reflux is greater if the following are present [16] [17]:

  • Lower grade of reflux, as opposed to a higher grade
  • Unilateral reflux, as compared to bilateral
  • Normal bladder function

Etiology

The most common cause for VUR is a congenital anatomical anomaly at the ureterovesical junction, where the length of the intravesical submucosal ureter is inadequate [1]. The intramural ureteral tunnel does not develop completely. As a consequence, the flap valve mechanism at ureterovesical junction fails, leading to a retrograde flow of urine from the bladder to ureter. Similar reflux of urine may occur even when the ureterovesical junction is normal in conditions such as obstruction of the bladder outlet or voiding dysfunction

Other infrequently encountered primary causes for VUR include:

  • Lack of sufficient detrusor backing
  • Paraureteral diverticulum / Hutch diverticulum
  • Lateral displacement of ureteral orifice

Secondary causes of VUR include:

Congenital reflux nephropathy is characterized by renal malformations such as renal agenesis, hypoplasia and dysplasia, that occur secondary to interactions between ectopic budding and poorly differentiated parts of metanephros.

Epidemiology

Evidence from various studies has showed that although <1% of the general population may have primary VUR, almost half of the children diagnosed with an UTI will also have VUR [2] [3]. Primary VUR is inherited as a dominant gene with a frequency of 1 in 600 and tends to run in families [4]. It is commonly diagnosed in childhood. The prevalence of VUR is difficult to determine as a large scale screening of populations by voiding cystourethrogram (VCUG) has not been performed so far. The majority of the available data suggests an incidence of 1% in normal children [2] [5] [6]. When considering all pediatric population, VUR has an estimated incidence of 1-2%. The incidence of VUR in black children is lower than the general average [3] [7]. In infancy, VUR is more severe and predominantly seen in male children [8] [9]. Most cases of primary VUR are familial. It is difficult to determine the true prevalence of VUR since most children are not symptomatic. The estimated prevalence of VUR is 0.4% to 1.8% in normal children [10]. The prevalence of VUR varies with multiple associated factors as follows [11] [12] [13]:

  • Children diagnosed with UTI: 30%
  • Siblings of individuals diagnosed with VUR: 46%
  • Infants diagnosed with pre-natal hydronephrosis:16%
  • Presence of duplex kidney: 46%
  • Presence of posterior urethral valves: 60%
  • Presence of cloaca: 60%
Sex distribution
Age distribution

Pathophysiology

The reflux of urine into the upper urinary tract from the bladder can potentially damage the kidneys and the ureter by causing bacterial infection or by increasing the hydrostatic pressure. Reflux of urine causes the seeding of upper urinary tract with bacteria present in the lower urinary tract. Recurrent infection of the renal parenchyma secondary to reflux may lead to scarring that would in-turn cause loss of kidney function and hypertension

The ureter enters at the trigone and courses obliquely in the bladder wall. The normal ratio for intramural tunnel length to ureteral diameter is 5:1. The filling of the bladder distends and thins the bladder wall, and at the same time, the intramural ureter also stretches, thins and compresses against the detrusor thus preventing a retrograde flow of urine. This is known as the flap-valve mechanism. This mechanism fails in VUR as the length of the intramural tunnel (intramural ureter) is shorter than normal, leading to reflux of urine into the upper urinary tract. 

VUR may be caused by bladder outlet obstruction, gastrointestinal dysfunction or learned voiding abnormalities such as Hinman syndrome or non-neurogenic neurogenic bladder. The intravesical pressure is elevated in all of these conditions. In children a high intravesical pressure may develop secondary to detrusor instability or detrusor hyperreflexia that may lead to secondary VUR or worsen the pre-existing VUR. It has been suggested that VUR may arise from physical stress that may be attributed to obstruction of vesicoureteral junction [14]. VUR is also thought to occur due to dysfunctional interactions between metanephric mesenchyme and the ureteric bud and/or abnormal budding of the ureter [15].

Prevention

Routine investigations for VUR may be avoided after the first episode of febrile UTI if the antenatal evaluation was appropriate and normal. Recurrent UTIs and/or a family history of VUR should prompt evaluation for a possible diagnosis of VUR.

Summary

Vesicoureteral reflux (VUR) is a condition wherein the urine, instead of passing towards the urethra, flows back into the ureters and reaches the renal pelvis. VUR can be found in association with various conditions such as renal dysplasia, hydronephrosis and urinary tract infection (UTI).

Patient Information

Vesicoureteral reflux is a condition wherein some of the urine in the bladder flows back towards the kidneys. It is usually diagnosed in childhood. It is likely to resolve by itself. In most cases it causes no symptoms. However, it is strongly suspected in children who have repeated infections of the urinary tract along with a fever. It can be treated using antibiotics for prophylaxis. Surgery may be needed in children that suffer from repeated infections of the urinary tract associated with fever, scarring of the kidneys or if the condition persists into teenage

References

Article

  1. Paquin AJ Jr. Ureterovesical anastomosis: the description and evaluation of a technique. J Urol. 1959 Nov;82:573-83.
  2. Mak RH, Kuo HJ. Primary ureteral reflux: emerging insights from molecular and genetic studies. Curr Opin Pediatr. 2003 Apr;15(2):181-5.
  3. Chand DH, Rhoades T, Poe SA, Kraus S, Strife CF. Incidence and severity of vesicoureteral reflux in children related to age, gender, race and diagnosis. J Urol. 2003 Oct;170(4 Pt 2):1548-50.
  4. Greenfield SP. Vesicoureteral reflux. AUA Update Series. 2007;26:30–9.
  5. Eccles MR, Jacobs GH. The genetics of primary vesico-ureteric reflux. Ann Acad Med Singapore 29 : 337 –345, 2000
  6. Lama G, Russo M, De Rosa E, Mansi L, Piscitelli A, Luongo I, Esposito Salsano M. Primary vesicoureteric reflux and renal damage in the first year of life. Pediatr Nephrol 15 : 205 –210, 2000
  7. Fanos V, Cataldi L. Antibiotics or surgery for vesicoureteric reflux in children. Lancet. 2004 Nov 6-12;364(9446):1720-2.
  8. Esbjörner E, Hansson S, Jakobsson B. Swedish Paediatric Nephrology Association. Management of children with dilating vesico-ureteric reflux in Sweden. Acta Paediatr. 2004 Jan;93(1):37-42.
  9. Sillén U. Vesicoureteral reflux in infants. Pediatr Nephrol. 1999 May;13(4):355-61.
  10. Bailey RR. Vesicoureteral reflux in healthy infants and children. Reflux Nephropathy 1979 59–61
  11. Sargent MA. What is the normal prevalence of vesicoureteral reflux? Pediatr Radiol. 2000 Sep;30(9):587-93.
  12. Skoog SJ, Peters CA, Arant BS Jr, Copp HL, Elder JS, Hudson RG, Khoury AE, Lorenzo AJ, Pohl HG, Shapiro E, Snodgrass WT, Diaz M. Pediatric Vesicoureteral Reflux Guidelines Panel Summary Report: Clinical Practice Guidelines for Screening Siblings of Children With Vesicoureteral Reflux and Neonates/Infants With Prenatal Hydronephrosis. J Urol. 2010 Sep;184(3):1145-51. doi:10.1016/j.juro.2010.05.066. Epub 2010 Jul 21. Review. Erratum in: J Urol. 2011 Jan;185(1):365.
  13. Zerin JM, Ritchey ML, Chang AC. Incidental vesicoureteral reflux in neonates with antenatally detected hydronephrosis and other renal abnormalities. Radiology. 1993 Apr;187(1):157-60.
  14. Beck AD. The effect of intra-uterine urinary obstruction upon the development of the fetal kidney. J Urol 105 : 784 –789, 1971
  15. Mackie G, Stephens F. Duplex kidneys: A correlation of renal dysplasia with position of the ureteral orifice. J Urol 114 : 274 –280, 1975
  16. Lenaghan D, Whitaker JG, Jensen F, Stephens FD. The natural history of reflux and long-term effects of reflux on the kidney. J Urol. 1976 Jun;115(6):728-30.
  17. Tamminen-Möbius T, Brunier E, Ebel KD, Lebowitz R, Olbing H, Seppänen U, Sixt R. Cessation of vesicoureteral reflux for 5 years in infants and children allocated to medical treatment. The International Reflux Study in Children. J Urol. 1992 Nov;148(5 Pt 2):1662-6.
  18. American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics. 1999 Apr; 103(4 Pt 1):843-52.

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Last updated: 2019-06-28 10:53