Basics
Description
Vesicoureteral reflux (VUR) occurs when urine passes backward from the bladder to the ureters or kidneys.
Epidemiology
Prevalence
VUR occurs in ¢ ¼1% of children. There are 2 different groups of patients:
- Those who were detected prenatally without any history of urinary tract infection (UTI)
- ¢ ¼20 " 30% of patients with prenatal hydronephrosis have VUR. Screening this population for VUR is controversial.
- The ratio of males to females in this group is 3:1. This ratio is believed to be caused by a period of high-pressure voiding in boys, which resolves by 18 months.
- Those who were detected after an acute UTI
- ¢ ¼30 " 50% of children with a febrile UTI will have VUR.
Risk Factors
Genetics
- 30% of siblings will have VUR (usually low-grade), and the great majority will have been asymptomatic with only rare renal scarring.
- Parents with VUR have a 60% chance of having children with VUR:
- Whether or not to screen siblings is controversial as low-grade VUR usually resolves without treatment or sequelae.
- One may elect to screen siblings with a history of recurrent febrile illnesses even in the absence of definitely diagnosed UTIs.
Pathophysiology
- VUR in combination with UTI can lead to pyelonephritis, renal scarring, and possibly end-stage renal disease.
- Primary VUR is classified into 5 grades by the International Reflux Study based on the voiding cystourethrogram (VCUG):
- Grade I: reflux into ureter
- Grade II: reflux into renal pelvis without dilation of calyces
- Grade III: blunting of calyces, mild dilation of ureter
- Grade IV: grossly dilated ureter, moderate calyceal dilation with maintained papillary impressions
- Grade V: grossly dilated ureter with loss of papillary impressions
- The grading scale is important because spontaneous resolution rates are very different between grades I " III and grades IV " V.
Etiology
- A combination of abnormal anatomy and abnormal voiding pressure:
- Primary VUR results from either a short ureteral tunnel through the bladder wall or transient high-pressure voiding, which occurs normally in the first 18 months of life.
- Patients with primary low-grade VUR can expect improvement and even resolution of the VUR with time as the ureteral tunnel grows or when bladder pressures decrease.
- Secondary VUR occurs when there is an associated lesion responsible for the abnormal anatomy or increased intravesical (bladder) pressure:
- Patients with secondary reflux require treatment of their primary problem and still may require surgery to treat their secondary reflux.
- Secondary reflux may occur in neurologically normal patients with bladder and bowel dysfunction, ureteroceles, posterior ureteral valves, and prune belly syndrome or in neurologically abnormal patients with spina bifida.
- The distinction between primary and secondary reflux is important because large prospective trials have been conducted on patients with primary reflux and it is not appropriate to extend those findings to patients with secondary reflux.
- Another important distinction is whether the diagnosis of VUR was made as a result of a prenatal diagnosis of hydronephrosis or whether the child presented with UTI.
Diagnosis
History
- Prenatal dilation of the urinary tract or UTI as presentation
- Family or sibling history of VUR
- Family history of UTI, suggestive of infection-susceptible uroepithelium
- Family history of renal failure
- Voiding history: age at toilet training
- Daytime or nighttime incontinence
- Frequency of urination
- Sensation of emptying the bladder completely
- Signs of bladder and bowel dysfunction:
- Urgency
- Frequency
- Damp underwear
- Associated constipation: frequency of bowel movements, suggestive of pelvic floor immaturity
- Evidence of holding urine during a bladder contraction:
- Squatting, crossing legs
- Compressing urethra with heel (Vincent curtsy)
Physical Exam
- Abdominal palpation (primarily to check for hard stool)
- Check for labial adhesions in girls
- Phimosis in boys
- Inspection and palpation of spine (possible neurogenic bladder)
- Blood pressure
Diagnostic Tests & Interpretation
Lab
A serum creatinine and urinalysis for proteinuria may be obtained if the renal ultrasound suggests significant renal scarring or in severe bilateral VUR.
Imaging
- Renal/bladder ultrasound
- Ultrasound is usually obtained following a febrile UTI, or if the patient had a prenatal diagnosis of hydronephrosis, between the 2nd day and 1st week of life. The ultrasound is not as sensitive as dimercaptosuccinic acid (DMSA) scan for renal scarring.
- The lack of hydronephrosis does not mean that the patient does not have VUR. However, renal bladder ultrasound is a useful tool for following renal growth.
- VCUG
- A contrast study is necessary for the 1st VCUG to delineate the urethral anatomy in boys and to accurately grade the reflux in both sexes.
- An age-appropriate volume should be instilled in the bladder. The voiding portion of the study is important because ¢ ¼20% of VUR can be missed if voiding is not observed.
- Follow-up VCUGs can be performed using radionuclide to decrease the radiation dose to the child.
- Whether to routinely perform a VCUG for a "first " febrile UTI in children aged 2 months to 2 years is controversial
- DMSA renal scan
- The most accurate way to diagnose pyelonephritis and renal scarring
- It is not possible to predict which patients will develop scarring after an acute episode (unless they have prior scarring, which is a risk factor for future scarring).
- If the diagnosis of upper tract infection versus cystitis is important, then the DMSA scan during an acute episode is useful.
- DMSA is not usually helpful with afebrile UTI.
- Some advocate using DMSA to identify high-risk patients requiring VCUG.
Differential Diagnosis
In the prenatally detected group, hydronephrosis can also be due to ureteropelvic or ureterovesical junction obstruction. The important task is to differentiate primary from secondary VUR so that the parents can be appropriately counseled.
Treatment
General Measures
- Four randomized controlled trials suggest that medical management (prophylactic antibiotics) and surgery have essentially equal outcomes in regard to hypertension, growth, and renal scarring. Surgery was more effective at preventing pyelonephritis.
- The rate of renal scarring was equal in the medical and surgical arms of the International Reflux Study. However, the timing of renal scarring was different: In the medically treated arm, new renal scars continued to form during 5 years of follow-up, whereas in the surgical arm, the renal scars stopped within 10 months of surgery. Surgery was 95% successful in correcting reflux with a 4% complication rate. Surgery involves creation of a longer muscular backing for the ureter to create a flap-valve mechanism.
- Patients with low-grade reflux should be maintained on prophylactic antibiotics and surgery delayed because grades I " III have a significant rate of spontaneous resolution. Patients with high-grade reflux (grades IV " V) should be initially maintained on prophylactic antibiotics, but earlier consideration for surgical correction should be given due to the lower rate of spontaneous resolution. Likewise, patients with reflux and renal scarring should be considered for earlier surgery because they have already shown a propensity toward UTI and renal damage.
- Antibiotic prophylaxis does not mean treatment-dose antibiotics. The antibiotics chosen are highly concentrated in the urine, and the use of high doses only selects out resistant organisms and leads to complications such as yeast infections. Amoxicillin at 10 " 15 mg/kg/24 h is used for the first 2 months of life, then trimethoprim/sulfamethoxazole (40 mg/200 mg/5 mL) at 0.25 mL/kg/24 h (equivalent to 2 " 3 mg/kg daily of trimethoprim) or nitrofurantoin at 1 " 2 mg/kg/24 h.
- Patients who are detected with VUR in infancy should probably have a contrast VCUG at 18 months to 2 years to determine if VUR has resolved.
- In toilet-trained children, maintenance of a regular voiding pattern and regular bowel movements decreases the risk of febrile UTI and increases the chance of VUR resolution.
- Patients being managed on antibiotic prophylaxis undergo annual follow-up nuclear VCUG to document improvement or resolution of VUR. Grading is less precise with nuclear VCUG, but the radiation dose is lower. A renal ultrasound is also obtained to follow renal growth and check for gross renal scars.
- Indications for crossing over to surgery are as follows:
- Patient or parent wishes
- Nonadherence with medical therapy
- Breakthrough infections while on medical therapy if a careful review of voiding habits demonstrates that bladder and bowel dysfunction is not responsible for the UTI. Lack of new renal scarring may also suggest that continued medical management is appropriate.
- New renal scarring
- Persistence of grades IV or V reflux after an appropriate period of antibiotic prophylaxis
- The use of injectable bulking agents has a 80 " 85% success 1 year after 1 treatment of low-grade VUR, with progressively decreasing success rate as the grade of VUR increases. Centers with more experience with injection have higher success rates. The minimally invasive nature of these treatments is balanced with a lower success rate. Deflux (dextranomer/hyaluronic acid) is the most commonly used injectable in the United States and is widely used in treating grades I " III VUR. Deflux treatment in higher grades of VUR and robotic and laparoscopic ureteral reimplantation are being explored in select patients.
- The use of continuous antibiotic prophylaxis has been questioned because although it decreases the risk of UTI for higher grade VUR, it has not been shown to decrease renal scarring compared to placebo. An NIH multi-institutional trial to determine the benefits of continuous prophylaxis versus placebo treatment is ongoing. The Swedish Reflux Trial showed a decreased rate of febrile UTI in girls with grades III " IV VUR who underwent injection therapy or prophylaxis, compared to those on surveillance. New renal scarring was less frequent in girls on prophylaxis compared to those on surveillance.
- The management of patients who continue to have VUR after several years of prophylactic antibiotics is controversial. Although most feel comfortable discontinuing antibiotics for boys with VUR after age 6 years because the risk of renal scarring is decreased and boys are at low risk for UTI, the adolescent girl is at increased risk for complications during pregnancy if she has a past history of UTI. The few studies on this subject seem to indicate that the patients with VUR and recurrent UTI are at risk for pregnancy-related complications whether or not the VUR has been surgically corrected, suggesting that the propensity toward UTI plays a more important role.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
Patients with renal scarring should have annual BP checks and urinalysis for proteinuria through adolescence.
Prognosis
- In primary VUR, 80 " 90% of grades I and II reflux, 70% of grade III, 40% of grade IV, and 25% of grade V resolve over a 5-year period.
- The annual rate of spontaneous resolution is between 15% and 20% for grades I " III.
- Bilateral reflux is less likely to resolve than unilateral reflux.
- Patients age 5 years or older at presentation are less likely to resolve than those who present at <5 years of age.
- Reflux that appears in the filling phase of VCUG ( "passive reflux " ) may be less likely to resolve than reflux that only appears during voiding phase.
- Ultimately, the goal is prevention of renal scarring rather than resolution of the reflux because low-pressure sterile reflux does not lead to renal scarring.
- Chronic kidney disease is very unlikely in the absence of bilateral grade III or higher VUR.
Additional Reading
- Brandstrom P, Neveus T, Sixt R, et al. The Swedish reflux trial: IV renal damage. J Urol. 2010;184(1):292 " 297. [View Abstract]
- Elder JS, Diaz M, Caldamone AA, et al. Endoscopic therapy for vesicoureteral reflux: a meta-analysis. I. Reflux resolution and urinary tract infection. J Urol. 2006;175(2):716 " 722. [View Abstract]
- Keren R, Carpenter M, Greenfield S, et al. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatrics. 2008;122(6):1409 " 1410. [View Abstract]
- Pennesi M, Travan L, Peratoner L, et al. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatrics. 2008;121(6):e1489 " e1494. [View Abstract]
- Peters C, Skoog S, Arant B Jr, et al. Summary of the AUA guideline on management of primary vesicoureteral reflux in children. J Urol. 2010;184(3):1134 " 1144. [View Abstract]
- Subcommittee on Urinary Tract Infection. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128(3):595 " 610. [View Abstract]
Codes
ICD09
- 593.70 Vesicoureteral reflux unspecified or without reflux nephropathy
- 753.4 Other specified anomalies of ureter
ICD10
- N13.70 Vesicoureteral-reflux, unspecified
- Q62.7 Congenital vesico-uretero-renal reflux
- N13.71 Vesicoureteral-reflux without reflux nephropathy
SNOMED
- 197811007 vesicoureteric reflux (disorder)
- 373637000 Congenital vesicoureterorenal reflux (disorder)
- 236615008 Primary vesicoureteric reflux (disorder)
- 236616009 Secondary vesicoureteric reflux (disorder)
FAQ
- Q: How soon after a UTI should the VCUG be performed?
- A: Once the patient is clinically stable and afebrile and sterile urine has been documented, the VCUG can be performed.
- Q: Why not operate immediately to repair the reflux when it is diagnosed?
- A: Depending on the grade of reflux, many cases will resolve in time.