Overview
Vesicoureteral Reflux (VUR)
1. Clinical Overview
Summary
Vesicoureteral Reflux (VUR) is the retrograde flow of urine from the bladder into the ureter and kidney. It is the most common urological abnormality in children and is found in ~30-40% of children investigated for febrile urinary tract infection (UTI). VUR is caused by abnormal development of the vesicoureteral junction (VUJ), resulting in a short intramural ureter and incompetent valvular mechanism. The major clinical concern is that VUR + UTI = Pyelonephritis → Renal Scarring → Reflux Nephropathy → Hypertension / Chronic Kidney Disease (CKD). Diagnosis is by Micturating Cystourethrogram (MCUG). Management ranges from antibiotic prophylaxis (most low-grade VUR resolves spontaneously) to surgical intervention (endoscopic injection or ureteric reimplantation) for high-grade or persistent VUR with breakthrough infections. [1,2]
Clinical Pearls
VUR is Common After Febrile UTI: Up to 30-40% of children with febrile UTI have VUR. Investigate as per NICE guidelines.
Most Low-Grade VUR Resolves: Grade I-III often resolves spontaneously with bladder maturation by age 5-7 years.
Infection + Reflux = Scarring: Sterile reflux is less harmful. The combination of infected urine entering the kidney causes pyelonephritis and renal scarring.
DMSA Scan Shows Scarring: Renal scarring is detected by DMSA scan, not ultrasound.
2. Epidemiology
Incidence
- Prevalence in Healthy Children: ~1%.
- Prevalence in Children with UTI: 30-40%.
- Prevalence in Siblings of Child with VUR: 30%. Screen siblings if less than 2 years old.
Demographics
- Sex: Female > Male overall (More UTIs → More detection). But males predominate in infants less than 1 year (often antenatally detected).
- Age: Often presents in infancy or early childhood with UTI.
- Family History: Strong genetic component. Autosomal dominant with incomplete penetrance.
3. Pathophysiology
Normal Vesicoureteral Junction
- The ureter enters the bladder at an oblique angle and passes through a submucosal tunnel.
- During bladder filling and voiding, the intramural ureter is compressed, acting as a one-way valve preventing reflux.
Mechanism of VUR
- Abnormal VUJ Development: Short or absent submucosal tunnel. VUJ entry angle too perpendicular.
- Incompetent Valvular Mechanism: During voiding (increased intravesical pressure), urine regurgitates up the ureter.
- Urine Refluxes into Ureter/Kidney: Degree of reflux depends on VUJ defect severity.
- VUR + Infection = Pyelonephritis: Bacteria from bladder ascend to kidney with refluxing urine.
- Renal Scarring (Reflux Nephropathy): Inflammatory damage to renal parenchyma. Particularly occurs in first 2-3 years of life. Scarring detected by DMSA.
- Consequences of Scarring: Hypertension, Proteinuria, Chronic Kidney Disease.
- Spontaneous Resolution: With bladder growth, the intramural ureter lengthens, improving the valvular mechanism. Low-grade VUR often resolves by age 5-7 years.
Secondary VUR
- Caused by high bladder pressures: Posterior Urethral Valves (PUV), Neuropathic bladder, Bladder Outlet Obstruction.
4. Classification (International Reflux Grading System)
| Grade | Description | Prognosis |
|---|---|---|
| I | Reflux into non-dilated ureter only. Does not reach renal pelvis. | Excellent. Usually resolves. |
| II | Reflux into renal pelvis WITHOUT dilation. Calyces normal. | Very good. Usually resolves. |
| III | Mild to moderate dilation of ureter, renal pelvis, and calyces. Minor blunting of fornices. | Good. ~70% resolve. |
| IV | Moderate dilation of ureter, pelvis, calyces. Clubbing of calyces. Ureter tortuosity. | Moderate. ~40% resolve. |
| V | Severe dilation. Gross tortuosity. Calyceal clubbing/obliteration. | Poor. Rarely resolves. Surgery often needed. |
5. Differential Diagnosis
| Condition | Key Features |
|---|---|
| Vesicoureteral Reflux | Retrograde flow on MCUG. Recurrent UTIs. Renal scarring on DMSA. |
| Posterior Urethral Valves (PUV) | Boys only. Bilateral hydroureteronephrosis. "Keyhole" bladder on USS. Secondary VUR common. |
| Ureteropelvic Junction (UPJ) Obstruction | Hydronephrosis WITHOUT hydroureter. No reflux on MCUG. |
| Ureterovesical Junction (UVJ) Obstruction | Hydroureter with dilated pelvis but obstruction at UVJ (not reflux). |
| Duplex Kidney with Ectopic Ureterocele | Upper pole hydronephrosis. Lower pole VUR. |
| Neuropathic Bladder | History of spina bifida. High bladder pressures → Secondary VUR. |
6. Clinical Presentation
History
Examination
Febrile UTI
Most common presentation. Fever, Irritability, Vomiting (especially infants).
Recurrent UTIs
Multiple episodes of cystitis or pyelonephritis.
Antenatal Hydronephrosis
VUR may be detected on postnatal investigation.
Family History
Sibling or parent with VUR.
Failure to Thrive
In severe cases with renal impairment.
Nocturnal Enuresis / Voiding Dysfunction
May coexist.
7. Investigations
Imaging Pathway (NICE Guideline)
Investigation after UTI depends on age, type of UTI (atypical, recurrent), and response to treatment.
| Investigation | Purpose |
|---|---|
| Ultrasound Kidney Ureter Bladder (KUB) | First-line. Assess kidney size, Hydronephrosis, Hydroureter, Bladder abnormalities. Does NOT diagnose VUR. Does NOT detect scarring. |
| Micturating Cystourethrogram (MCUG) | Gold Standard for VUR. Contrast instilled into bladder via catheter, X-rays taken during voiding. Shows reflux and grades it. Also assesses urethra (PUV in boys). |
| DMSA Scan (Tc-99m Dimercaptosuccinic Acid) | Detects Renal Scarring (Reflux Nephropathy). Also differential kidney function. Best performed 4-6 months after acute pyelonephritis. |
| MAG3 Renogram | Assesses drainage (UPJ/UVJ obstruction). Not primarily for VUR. |
When to Investigate (NICE CG54 Summary)
| Age | Atypical UTI | Recurrent UTI |
|---|---|---|
| less than 6 months | USS (Acute), DMSA (4-6mo), MCUG | USS, DMSA, MCUG |
| 6 months - 3 years | USS (Acute), DMSA | USS, DMSA |
| >3 years | USS (Acute), DMSA | USS, DMSA |
| Atypical UTI: Severely ill, Poor urine flow, Non-E.coli organism, Raised Creatinine, No response to antibiotics 48h. |
8. Management
Management Algorithm
CHILD WITH VUR (Diagnosed on MCUG)
↓
ASSESS GRADE + CLINICAL PICTURE
(Unilateral vs Bilateral, Scarring on DMSA,
Recurrent Infections)
↓
LOW GRADE (I-III)
WITHOUT SCARRING / BREAKTHROUGH UTI
┌────────────────┴────────────────┐
│ CONSERVATIVE MANAGEMENT │
│ - Regular urine surveillance │
│ (Culture if febrile) │
│ - Antibiotic Prophylaxis │
│ (Trimethoprim 1-2mg/kg nocte │
│ OR Nitrofurantoin) │
│ (Controversial - Consider) │
│ - Avoid constipation │
│ - Encourage regular voiding │
│ - Most Grade I-III resolve │
│ by age 5-7 years │
└─────────────────────────────────┘
↓
HIGH GRADE (IV-V)
OR BREAKTHROUGH UTIS
OR NEW RENAL SCARRING
┌────────────────┴────────────────┐
ENDOSCOPIC SURGICAL
(STING / Dextranomer) (Ureteric Reimplantation)
↓ ↓
- Injection of bulking - Open or Laparoscopic
agent at VUJ (Deflux) - Redo of VUJ with
- Day case procedure longer submucosal tunnel
- 70-80% success Grade I-III - 95%+ success rate
- Lower success higher grade - More invasive
Conservative Management
| Component | Notes |
|---|---|
| Antibiotic Prophylaxis | Trimethoprim 1-2mg/kg at night OR Nitrofurantoin. Prevents UTI while awaiting spontaneous resolution. Controversial (RIVUR trial showed benefit for reducing UTI but not scarring). |
| Surveillance | Regular urine cultures if febrile. Repeat imaging (USS, DMSA) as indicated. |
| Bladder and Bowel Dysfunction Management | Treat constipation (common comorbidity). Encourage regular, complete voiding. |
| Follow-Up | Repeat MCUG after 1-2 years (if appropriate) to assess resolution. |
Surgical Treatment
Endoscopic Injection (STING / Deflux)
- Technique: Cystoscopy + Injection of bulking agent (Dextranomer/Hyaluronic acid – Deflux) at VUJ to create a "nipple" that improves valvular mechanism.
- Advantages: Minimally invasive, Day case.
- Success Rate: 70-80% for low-grade. Lower for high-grade.
- May need repeat injections.
Ureteric Reimplantation
- Technique: Open or Laparoscopic. The ureter is reimplanted into the bladder with a longer submucosal tunnel (Cohen, Lich-Gregoir, Politano-Leadbetter techniques).
- Indications: High-grade VUR, Failed endoscopic treatment, Breakthrough infections with scarring.
- Success Rate: >95%.
- Risks: Ureteric obstruction, Bleeding, Contralateral reflux.
9. Complications
| Complication | Notes |
|---|---|
| Recurrent Pyelonephritis | Febrile UTI. Risk of renal damage. |
| Renal Scarring (Reflux Nephropathy) | Detected by DMSA. Permanent parenchymal damage. |
| Hypertension | Due to renin-angiotensin activation from scarred kidney. |
| Chronic Kidney Disease (CKD) | Progressive loss of renal function. VUR is a leading cause of CKD in children. |
| Proteinuria | Sign of glomerular damage. |
| End-Stage Renal Disease (ESRD) | Rare but possible in severe bilateral reflux nephropathy. |
10. Prognosis and Outcomes
- Grade I-III: ~70-90% spontaneous resolution by age 5-7 years.
- Grade IV-V: Lower resolution rates (~30-40% for Grade IV). Surgery often required.
- Scarring Prevention: Early diagnosis and treatment of UTIs is key to preventing scarring.
- Long-Term Follow-Up: Children with renal scarring need lifelong BP and renal function monitoring.
11. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| UTI in Children (CG54) | NICE | Imaging pathway for UTI. MCUG for specific indications. Antibiotic prophylaxis. |
| VUR Management | AUA / EAU | Grading, Conservative vs Surgical approach. |
Landmark Trials
- RIVUR Trial (NEJM 2014): Antibiotic prophylaxis reduces UTI recurrence but not renal scarring.
12. Patient and Layperson Explanation
What is Vesicoureteral Reflux?
VUR is a condition where urine flows backwards from the bladder up into the kidneys. Normally, urine only travels one way – from the kidneys, down the tubes (ureters) to the bladder, and out. In VUR, the valve at the junction doesn't work properly.
Why is it important?
If your child gets a bladder infection (UTI), the bugs can travel up to the kidneys with the refluxing urine. This can cause a kidney infection (pyelonephritis), which can damage the kidneys over time (scarring). Scarring can lead to high blood pressure or kidney problems in the future.
How is it treated?
- Mild cases: Often just watchful waiting. Many children outgrow it as the bladder grows.
- Antibiotic Prophylaxis: A low dose of antibiotic at night can help prevent infections.
- Surgery: If reflux is severe or causes problems, we can fix it with a small procedure (injection) or an operation.
What happens long-term?
Most children with VUR do very well, especially if diagnosed early and infections are prevented. Regular check-ups and blood pressure monitoring are important.
13. References
Primary Sources
- NICE Clinical Guideline CG54. Urinary tract infection in under 16s: diagnosis and management. 2017.
- RIVUR Trial Investigators. Antimicrobial Prophylaxis for Children with Vesicoureteral Reflux. N Engl J Med. 2014;370:2367-76. PMID: 24795142.
14. Examination Focus
Common Exam Questions
- Grading: "Describe Grade III VUR."
- Answer: Reflux with mild-moderate dilation of ureter and renal pelvis. Minor blunting of fornices. Calyces not grossly clubbed.
- Investigation: "Gold standard investigation for diagnosing VUR?"
- Answer: Micturating Cystourethrogram (MCUG).
- Scarring Assessment: "How do you assess for renal scarring?"
- Answer: DMSA Scan (not Ultrasound).
- Natural History: "What percentage of Grade I-III VUR resolves spontaneously?"
- Answer: ~70-90% by age 5-7 years.
Viva Points
- RIVUR Trial: Know that prophylaxis reduces UTI but not definitively proven to reduce scarring.
- Secondary VUR: Mention Posterior Urethral Valves (PUV) as a cause in boys.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.