VUR = retrograde flow of urine from bladder to ureter

Etiologies

• Weak trigone → UO migrates laterally with short submucosal tunnel
• Normally bladder contraction compresses the oblique intravesical ureter to prevent reflux 
  
• PUV (50%), MCDK (contralateral VUR in 20-40%)
• Bowel-bladder dysfunction (BBD, dysfunctional voiding syndrome) - high intravesical pressure and high PVR (treat with behavioral therapy)

Natural history

• VUR in ~ 1% of healthy children; in 70% of infants with UTI
• Infancy - 76% male
• Later life - 85% female 
• Some genetic component - 20-30% incidence in siblings/children
• Peak age of diagnosis 3-6 yo; presents with UTI
• Spontaneous resolution in lower grades and younger age at presentation - can "outgrow" VUR as bladder/trigone strengthens in musculature
• 80-90% resolve at 5 years for grade I/II VUR
• 75% for grade III

Complications

• UTI + reflux → pyelonephritis
• Sterile reflux is benign
• Renal scarring from febrile UTIs, can → nephropathy and HTN
• Risk of renal scarring decreases with age
• Risk of renal scarring highest with Grade IV/V reflux
• Prompt treatment of febrile UTI can minimize scarring

VUR is suggested by prenatal hydronephrosis (15% risk of having VUR)

Indications for urinary tract imaging

• Febrile UTI between 2 mo and 2 yr of age
• Abnormal UA + positive culture (lower threshold per AAP guidelines - > 50,000 CFUs/ml)
• May forgo VCUG on 1st febrile UTI
• **hide**(lots of debate...AAP recommends VCUG after 2nd febrile UTI. May be missing VUR after 1st febrile UTI but argue that this is low grade/not as clinically significant)
• **hide**

  	Responds to treatment within 48 hrs	Atypical UTI	Recurrent UTI
  < 6 mo
  6 mo to 3 yrs
  > 3 yrs		US during infection

• Prenatal hydro (although hydronephrosis without hydroureter unlikely to indicate reflux as etiology)

Work up

• Work-up after 1 month of age (reason?? ___)
• Renal ultrasound
• If hydro on US, → renal scan (DMSA) to monitor renal scarring
• **hide**Practically DMSA tracer hard to obtain
• If high-grade (III-V) hydro or structural abnormality, → voiding cystourethrogram (VCUG)
• Criteria for VCUG controversial; no strong evidence
• UA/UCx to r/o infection before cystogram - wait at least a week if infected
• If can see catheter on films, poor quality VCUG (contrast too dilute)
• "Top-down" approach (DMSA first) to avoid VCUG and only identify clinically significant VUR in those at greatest risk of renal scarring
• If DMSA already positive and hydro III-V, may not need to order VCUG (would only miss VUR in 4% of children < 1 yr with positive DMSA)
• If DMSA negative, unlikely to see renal scars develop after age 5 - don't need to chase identification of VUR with VCUG if renal function is likely preserved.
• Disadvantages: miss 5-30% of VUR, kids will likely not be on abx ppx
• "Bottom-up" approach (more common/traditional)
• If febrile UTI, get VCUG
• If high grade VUR, get DMSA
• Disadvantage - may detect clinically insignificant VUR
• Check Cr if b/l hydro/renal abnormality (or in solitary kidney)

Goal of treatment is to prevent febrile UTI → renal scarring, not to correct VUR

• AUA guidelines: abx ppx (CAP) for children < 1 yo with: h/o fUTI + VUR, or no fUTI + Gr 3-5 VUR (optional for Gr 1-2), or VUR with bowel-bladder dysfunction.
• Data shows ~50% reduction in UTI
• Medical therapy - continuous antibiotic prophylaxis (CAP) at 1/4 - 1/3 dose, until reflux resolves
• < 2 mo: amoxicillin (macrobid causes hemolytic anemia; bactrim causes kernicterus)
• > 2 mo: bactrim (liver can metabolize now, and does not alter gut flora)
• Macrobid also used but lower PO tolerance. macrobid not absorbed into tissue so less side effects; would not be used to treat febrile UTI so not as big of a deal if they become resistant to it?
• Keflex can be used but is a/w high rates of resistance. 25 mg/kg/day, once daily
• Keflex vs amoxicillin is based on antibiogram: east coast amox, west coast keflex
• Treat underlying causes e.g. BBD (bowel bladder dysfunction); triple voiding/bladder training
• Consider trial off antibiotics after potty training if low risk (low grade, circumcised male); later if higher risk (female, high grade)
• Surgical therapy - consider if breakthrough UTI/failure to comply with CAP, unlikely to have spontaneous resolution; persistent high-grade (IV–V) VUR
• Ureteral reimplantation (95% successful)
• Need to wait until at least 1 y old so that bladder is large enough
• Endoscopic injection of bulking agent (74% success) - inject 6 o'clock submucosal position (PDMS/other)
• 70-90% for Gr I-III, ~60% for Gr IV-V
• Vesicostomy if too young for above
• Males < 1 yo: optional circumcision to reduce risk of UTI (from 1% to 0.1%)
• Medical vs. surgical therapy: renal scarring is similar, but medical therapy has 2.5x higher incidence of febrile UTI

Follow-up

• UA and renal ultrasound q year to monito renal growth
• VCUG q 1-2 years: single negative VCUG can establish resolution of VUR
• DMSA renal scan if: elevated Cr, renal abnormality on US, or high-grade VUR/breakthrough UTI
• After surgery
• Renal/bladder US at 4-6 weeks to check for ureteral obstruction, then 3, 12, and 24 mo
• VCUG can be deferred post-reimplant due to high success rates
• VCUG 3 months after bulking injection (while still on abx) to check for resolution