VUR typically presents in childhood. 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 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. 

• Recurrent Urinary Tract Infection

  Females have a high risk of dysfunctional urination and recurrent urinary tract infections. [columbiadoctors.org]

  In contrast to the primary form, secondary VUR arises due to a malfunction within the urinary system. Most commonly, recurrent urinary tract infections (UTIs) are implicated as the etiological agents of secondary VUR. [news-medical.net]

  Girls have a high risk of dysfunctional urination and recurrent urinary tract infections. Children with VUR are prone to kidney infections because the backward flow of urine can move bacteria from the bladder to the upper urinary tract. [columbiaurology.org]

  The incidence of urinary tract infection is 8% in females and 2% in males 2. Among children with urinary tract infections, incidence of vesicouretic reflux rises to ~ 25-40%. [radiopaedia.org]

• Recurrent Infection

  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. [symptoma.com]

  Symptomatic reflux (recurrent infections, impaired renal growth, renal scarring) is treated with endoscopic injection of a bulking agent (eg, dextranomer/hyaluronic acid) or ureteral reimplantation. [msdmanuals.com]

  Females have a high risk of dysfunctional urination and recurrent urinary tract infections. [columbiadoctors.org]

  Reflux associated with recurrent infections of the urinary tract (UTI) is the most common cause of kidney damage or scarring in children. [med.unc.edu]

• Diarrhea

  Infants may indicate a UTI by showing a fever, diarrhea, no appetite, irritability or “failure to thrive,” meaning lower weight and slower growth than normal. Children also often have nonspecific symptoms. [denverurology.com]

  Diarrhea. Contact the doctor if several of your baby's stools are especially loose or watery. Vomiting. Occasional spitting up is normal. [mayoclinic.org]

  An infant who is refusing food, eating poorly, is lethargic, difficult to wake up, has inconsolable crying, diarrhea, or vomiting also needs medical attention. [medicalnewstoday.com]

  Your baby is suffering from diarrhea. Your baby is cranky and moody, at times he cries a lot or otherwise very drowsy. [momjunction.com]

  […] the diagnosis of UTI in 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 [emedicine.com]

• Suggestibility

  The sensitivity and specificity of ultrasound in suggesting VUR were 40% and 76%, respectively. The positive predictive value of ultrasound in suggesting VUR was 32%; the negative predictive value was 82%. [adc.bmj.com]

  As with the history, few findings on physical examination suggest VUR or UTI. Fever, flank or abdominal tenderness, or an enlarged palpable kidney may be present. See Clinical Presentation for more detail. [emedicine.com]

  Interestingly, a 2010 study suggested that the compliance rate for merely filling the prescription was only 40%, suggesting that many patients placed on antibiotic prophylaxis never receive the medication [54]. [pediatricurologybook.com]

  The following procedures may be used to diagnose VUR: Cystography Fluoroscopic voiding cystourethrogram (VCUG) Abdominal ultrasound Technetium-99m Dimercaptosuccunic Acid (DMSA) ScintigraphyAn abdominal ultrasound might suggest the presence of VUR if [en.wikipedia.org]

• Irritability

  Also let the doctor know if your baby is persistently irritable or has periods of inconsolable crying. Diarrhea. Contact the doctor if several of your baby's stools are especially loose or watery. Vomiting. Occasional spitting up is normal. [mayoclinic.org]

  Other clinical manifestations that might help with diagnosis and management Neonates can present with jaundice, vomiting, and irritability along with fever and failure to thrive. [clinicaladvisor.com]

  […] ureter Ureterocele Iatrogenic References: [1] [2] [3] [4] [5] Clinical features Suspected in the prenatal period when hydronephrosis is detected on routine antenatal ultrasound Postnatal presentation Recurrent febrile urinary tract infections Neonates : irritability [amboss.com]

  Infants may indicate a UTI by showing a fever, diarrhea, no appetite, irritability or “failure to thrive,” meaning lower weight and slower growth than normal. Children also often have nonspecific symptoms. [denverurology.com]

  Avoid juices and soft drinks as they can irritate the bladder. Place a warm blanket or towel over your child’s abdomen to ease pain or pressure. [webmd.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]

• Kidney Failure

  This may lead to kidney failure, which can occur quickly (acute kidney failure) or may develop over time (chronic kidney disease). [mayoclinic.org]

  Other symptoms include flank pain and hypertension, uremia, and kidney failure in advanced cases of reflux nephropathy. [amboss.com]

  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]

  However, kidney damage may be permanent. If only one kidney is involved, the other kidney should keep working normally. Reflux nephropathy may cause kidney failure in children and adults. [nlm.nih.gov]

• 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]

  Children with UTI may have fever, abdominal or flank pain, dysuria, frequency, urgency, wetting accidents, or rarely hematuria. [msdmanuals.com]

• Renal Insufficiency

  […] ultrasonography reveals scarring or a urinary tract anatomic abnormality Laboratory abnormalities may include proteinuria, sodium wasting, hyperkalemia, metabolic acidosis, renal insufficiency, or a combination. [msdmanuals.com]

  Some children with VUR remain entirely asymptomatic, while others may develop pyelonephritis, renal scarring, and potentially progressive renal insufficiency. [dovepress.com]

  The goal of VUR treatment is to prevent pyelonephritis and its sequelae such as renal parenchymal injury, hypertension, and chronic renal insufficiency. [pediatricurologybook.com]

  If infected urine flows back into the kidney it has the potential to cause scarring of the kidney (also known as "atrophy") with possible long-term side effects of hypertension, proteinuria and renal insufficiency. [ucdenver.edu]

• Nocturnal Enuresis

  For older children, symptoms can include nocturnal enuresis (bedwetting) or other urinary problems, high blood pressure, hydronephrosis, an abdominal mass from the swollen kidney, protein in the urine, and kidney failure. Diagnosis. [urology.ucla.edu]

  In addition, toilet-trained children should be assessed at each visit for constipation and infrequent voiding, incontinence, urinary urgency, and nocturnal enuresis, which are common signs of elimination dysfunction, and treated as needed with behavioral [msdmanuals.com]

  Other symptoms might include the following: • Bedwetting (nocturnal enuresis) • Distention in the abdomen (caused by hydronephrosis) • Failure to thrive • High blood pressure (hypertension; caused by kidney damage) • Hydronephrosis (collection of urine [rchsd.org]

• Ureteral Disorder

  Ureteral disorders occur when ureters become blocked or injured, which affect the flow of urine to the bladder. Read more about the ureter function. [efacyquxirufome.xpg.uol.com.br]

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

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:

• Trimethoprim/sulfamethoxazole
• Nitrofurantoin
• Cephalexin
• Amoxicillin (Infant age group) 

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.

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

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:

• Cystitis
• UTI
• Neurogenic bladder
• Obstruction of the bladder outlet
• Detrusor instability

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.

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%

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].

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.

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).

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. 

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.