Sanjay S. Kasturi, MD
BASICS
DESCRIPTION
• Vesicoureteral reflux (VUR) is defined as retrograde passage of urine from the bladder into the ureter and/or renal pelvis and calyces
• VUR in the presence of bacteria is a risk factor for pyelonephritis and may lead to upper-tract pathology. It may be unilateral or bilateral, primary or secondary
• A more common problem in children, it can be associated with significant morbidity in adults and may be an uncommonly unrecognized cause of hypertension (HTN) in this population
EPIDEMIOLOGY
Incidence
• 5% of adults have VUR
• Female > male
RISK FACTORS
• 85% of childhood reflux occurs in girls; likely to be similar in adults
• Family history of VUR
• Conditions that predispose to secondary VUR (eg, neuropathic bladder)
Genetics
Having a parent or sibling with VUR increases the risk of childhood VUR
PATHOPHYSIOLOGY
• Primary VUR (1)
– Failure of development or breakdown of the distal ureteral antireflux mechanism
– Normally, the distal 4–5 cm of the ureter courses through the muscular wall of the bladder before reaching the bladder trigone
– This tunnel prevents reflux of urine
– Congenital deficiency of the intravesical tunnel is the most common etiology
• Secondary VUR
– Disorders that cause elevated intravesical pressure: BPH, spinal cord injury, MS, and other neurologic diseases
– Patients who have undergone urinary diversion (ileal conduit) or bladder replacement (orthotopic neobladder, catheterizable diversions) commonly have VUR
– Bacterial cystitis can often cause transient ureteral reflux due to inflammation
– Genitourinary TB can cause the ureteral orifices to become fixed and relatively patulous
• International Reflux Study Committee classifies VUR into 5 grades:
– Grade I: Reflux partly up to the ureter
– Grade II: Reflux up to the pelvis and calyces without dilatation; normal calyceal fornices
– Grade III: Same as grade II, but with mild dilatation and tortuosity of the ureter and minimal blunting of the fornices
– Grade IV: Moderate dilatation and tortuosity of the ureter, pelvis, and calyces; complete blunting of fornices
– Grade V: Gross dilatation and tortuosity of the ureter, pelvis, and calyces; absent papillary impressions in the calyces
• Mild reflux: Grades I and II
• Moderate reflux: Grade III
• Severe reflux: Grades IV and V
• Reflux associated with diversions such as ileal conduit is considered to be low pressure with minimal long-term damage to upper tracts.
ASSOCIATED CONDITIONS
• See causes of high bladder storage pressure mentioned above
• Typically seen in refluxing anastomosis: Neobladders, ileal conduits, renal transplantations
GENERAL PREVENTION
None; Long-term renal damage can be limited by appropriate prevention of infection and management of secondary cause of VUR
DIAGNOSIS
HISTORY
• History of VUR in childhood
• Family history of VUR
• Recurrent UTIs
• Simple cystitis leading to fever and flank pain suggestive of pyelonephritis
• Lower urinary tract voiding symptoms, suggesting outlet obstruction or neuropathic bladder
PHYSICAL EXAM
• CVA tenderness with pyelonephritis
• Digital rectal exam for BPH
• Palpable bladder
• Neurologic impairment
• HTN (if renal compromise)
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Blood testing is not necessary, except for severe cases in which renal function should be evaluated
• Proteinuria (if renal compromise)
• Urine analysis and culture should demonstrate the presence of infection if the patient is symptomatic:
– Between infections, the urine will often be normal
Imaging
• US can show hydroureteronephrosis dependent on severity of VUR
• VCUG: Definitive test for identifying and grading the severity of reflux. It may also point toward the cause of VUR
• A nuclear medicine cystogram (indirect VCUG):
– Can be performed with MAG3
– Provides less anatomic information than the VCUG but does not require catheterization
Diagnostic Procedures/Surgery
Video urodynamic studies combine the information provided by the VCUG with physiologic information on bladder filling and voiding
Pathologic Findings
• Renal lesions (scarring) can be associated with higher grades of reflux
• Chronic scarring may, over time, cause HTN
DIFFERENTIAL DIAGNOSIS
• Other causes of flank (loin) pain and infection (eg, renal colic, ureteropelvic junction obstruction) (see Section I: “Flank Pain”)
• Other causes of hydroureteronephrosis or ureteral obstruction (See Section I: “Hydronephrosis/Hydroureteronephrosis [Dilated Ureter/Renal Pelvis], Adult”)
TREATMENT
GENERAL MEASURES
• Treatment of secondary VUR is directed at the primary cause (management of BPH, treatment of UTI, etc.)
• Early treatment of cystitis can prevent progression to pyelonephritis
MEDICATION
First Line
• Patients with recurrent UTI may benefit from prophylactic antibiotics
• Primary asymptomatic adult VUR does not otherwise require ongoing medical therapy as risk of progressive renal impairment is low
• Pregnant women with known VUR should be given antibiotic prophylaxis until delivery (eg, amoxicillin 250 mg/d PO) (2)
Second Line
• Secondary VUR may benefit from medical treatment of underlying cause:
– Anticholinergic preparations in detrusor overactivity
– α-Blockade or 5α-reductase inhibition in bladder outlet obstruction
SURGERY/OTHER PROCEDURES
• Primary VUR rarely requires surgical intervention in adults; however, where indicated procedures include:
– Endoscopic treatment: Injection of bulking agents below the ureteral orifice:
Initial results are good; however, long-term follow-up is scant
– Several agents have been used for endoscopic correction of VUR:
Polytetrafluoroethylene (Teflon)
Cross-linked bovine collagen, dextranomer/hyaluronic copolymer (Deflux)
Since the FDA approval of Deflux in 2001, this has been the most commonly used injectable agent for VUR
– Ureteric reimplantation can be undertaken transvesically, extravisually, or by a combination of both:
Some common techniques include: Cohen cross-trigonal, Politano–Leadbetter, Lich–Gregoir (extravesical) reimplantations
ADDITIONAL TREATMENT
Additional Therapies
Additional therapeutic options in the treatment of the underlying condition for secondary VUR include intradetrusor botulinum toxin and sacral neuromodulation
Complementary & Alternative Therapies
Some data suggest cranberry juice and live-culture yogurt can be effective in preventing UTI
ONGOING CARE
PROGNOSIS
Depends on underlying etiology and severity of VUR
COMPLICATIONS (3,4)
• Chronic pyelonephritis
• Reflux nephropathy
• Renal impairment rare in primary VUR unless pre-existing from childhood, but can be encountered in secondary VUR
• UTI
• Urolithiasis
FOLLOW-UP
Patient Monitoring
• Medical follow-up is unnecessary in patients without HTN or proteinuria, unless the patient develops recurring infections, at which point repeat workup is needed
• Patients with intrinsic renal disease due to prior reflux (in childhood) require follow-up of BP, creatinine, and urine protein
Patient Resources
http://kidney.niddk.nih.gov/kudiseases/pubs/vesicoureteralreflux/
REFERENCES
1. Bailey RR, Lynn KL, Robson RA. End-stage reflux nephropathy. Ren Fail. 1994;16(1):27–35.
2. El-Khatib M, Packham DK, Becker GJ, et al. Pregnancy-related complications in women with reflux nephropathy. Clin Nephrol. 1994;41(1):50–55.
3. Hall MK, Hackler RH, Zampieri TA, et al. Renal calculi in spinal cord-injured patient: Association with reflux, bladder stones, and Foley catheter drainage. Urology. 1989;34(3):126–128.
4. Zhang Y, Bailey RR. A long-term follow up of adults with reflux nephropathy. N Z Med J. 1995;108(998):142–144.
ADDITIONAL READING
• Buckley O, Geoghegan T, O’Brien J, et al. Vesicoureteric reflux in the adult. Br J Radiol. 2007;80(954):392–400.
• Murphy AM, Ritch CR, Reiley EA, et al. Endoscopic management of vesicoureteral reflux in adult women. BJU Int. 2011;108(2):252–254.
See Also (Topic, Algorithm, Media)
• Heikel–Parkkulainen Reflux Classification System
• Hydronephrosis/Hydroureteronephrosis (Dilated Ureter/Renal Pelvis), Adult
• Reflux Nephropathy
• Pyelonephritis, Chronic
• Urinary Tract Infection (UTI), Adult Female
• Urinary Tract Infection (UTI), Adult Male
• Urinary Tract Infection (UTI), Complicated, Adult
• Vesicoureteral Reflux, Adult Image 
• Vesicoureteral Reflux, Pediatric
CODES
ICD9
• 593.70 Vesicoureteral reflux unspecified or without reflux nephropathy
• 593.71 Vesicoureteral reflux with reflux nephropathy, unilateral
• 593.73 Other vesicoureteral reflux with reflux nephropathy NOS
ICD10
• N13.70 Vesicoureteral-reflux, unspecified
• N13.721 Vesicoureter-reflux w reflux neuropath w/o hydrourt, unil
• N13.729 Vesicoureter-reflux w reflux nephropathy w/o hydrourt, unsp
CLINICAL/SURGICAL PEARLS
Women with VUR tend to present with infections, while men tend to present with HTN and proteinuria.