Vesicoureteric reflux and UTI

Key points

Urinary tract infection (UTI)

11% girls have by age 16

3.6% boys

Boys more likely to have in 1st year of life compared to girls

Neonates - urosepsis can lead to meningitis

NICE guidance definitions:

>10^5 pure growth bacterial colony forming units/ml is diagnostic of UTI

Atypical UTI includes:

• Sepsis

• Obstruction at any level

• Renal failure

• Atypical/resistant organisms

Recurrent UTI:

• 3+ lower UTI

• 2+ Upper UTI or 1 upper + 1 lower

NICE Guidance summaries:

Microscopy result interpretation

NICE imaging summary:

<6 months old

Atypical or Recurrent (>3 in 1 year) get USS acute, MCUG, DMSA

Typical get USS in 6 weeks

6 months to 3 years

Same as above but:

No MCUG in any circumstance

Get USS at 6 weeks for recurrent instead of acute

Older than 3 years

No imaging for typical UTI

Only acute USS for atypical UTI

Only USS in 6 weeks + DMSA for recurrent

Management

Start with basics

Advise cranberry juice (D Mannose) etc

In girls - vaginal pooling if improper toilet posture

Klebsiella, proteus infection in boys due to foreskin colonisation - check retractile

3 days antibiotics for lower tract infection

7-10 days for upper tract infection

(Febrile UTI is hallmark of upper tract infection)

Vesicoureteric Reflux (VUR)

Primary: Abnormal VUJ + failure of flap/valve mechanism of ureter in submucosal tunnel - laterally sited ureteric orifice (UO)

Secondary: Bladder dysfunction + high pressure

Family predisposition

30% chance of siblings having - should do USS only for sibling

50% chance of child of affected parent having

X-linked variant identified

Children <4 years greater risk of renal scarring

Mild/Moderate renal scarring - likely caused by UTI

Severe scarring - likely congenital - abnormal interaction between ureteric bud and metanephros

Ransley theory: was it renal dysfunction causing UTI or other way around

If patient with recurrent UTI and normal USS, suspect non-dilating VUR (grades 1-2) - reasonable to investigate in girls who may benefit from STING

Criticism of NICE guidelines: misses subset of patients with VUR

Standard approach of investigating for VUR - bottom up

MCUG first - only do DMSA if VUR found

Top down approach

In child with febrile UTI -

DMSA first - only if scarring found do MCUG/Indirect cystogram - proponents suggest if no scarring there is no need to check for reflux

Indirect cystogram only for toilet trained children

Seeing ureter on MAG3 = standing column

Grading of VUR:

Grade I: Reflux into the ureter only, without reaching the renal pelvis without dilation

Grade II: Reflux into the ureter, renal pelvis, and calyces without dilation

Grade III: Mild dilation

Grade IV: Moderate dilation with blunting of the calyces

Grade V: Severe dilation and tortuosity of the ureter + intraparenchymal reflux

Grades 1-3 VUR resolves spontaneously in 5 years in reasonable proportion

4 unlikely and 5 will not resolve

Management:

Always start with basics:

Fluid intake

Tretaing constipation

Toileting and bladder trainign advice

Antibiotics (see studies below)

Indications for surgery for VUR:

• Breakthrough episodes of pyelonephritis

• Progressive renal scarring/impaired renal growth

• Persistent VUR in a female nearing puberty

Bulking agent injection to UO:

Examples include Deflux® (Hyaluronic acid/Dextranomer - dissolvable) and Teflon® (no longer used due to concerns about scarring in area and migration of agent)

Hydrodistension Implantation Technique (HIT) is intraluminal injection of agent

Subureteric Transurethral INjection (STING) is submuscular

Do USS 3-4 months post STING/HIT to check for obstruction

Can stop antibiotics after STING/HIT

STING resolves reflux at about 90% grade 1, decreasing approx 10%/grade until 60%

In summary higher success for lower VUR grades

Ureteric Hydrodistension grading:

Grade 0: Slit-like, no distension

Grade 1: Mild distension

Grade 2: Distends but lumen (extra-vesicle ureter) is not visible

Grade 3: Distends and lumen is visible

Ureteric Reimplantation:

Lich-Gregoir - Extravesical - ureter tunnelled in from outside

Cohen cross trigonal - intravesical - bladder split in midline - ureter cored out and tunnelled across to other side of trigone

Politano-Leadbetter - Same as Cohen but not cross trigonal - implant just above original UO

Needs 4:1 submucosal tunnel length to ureter diameter ratio - may need plication - resection is acceptable but risks devascularising ureter

Similar success rates for each

Overall reimplant approximately 98% success except grade 5: 80%

Long term follow up

VUR resolved + no nephropathy - discharge

VUR resolved + nephropathy - lifelong follow up

VUR persisting beyond puberty - do STING/reimplant in symptomatic females due to risk of pyelonephritis in pregnancy

Important VUR studies

RIVUR study USA

600 children (550 girls, most with grade 2-3 reflux)

Antibiotics vs placebo

0.55 relative risk with antibiotics

Swedish reflux trial

203 children (128 girls and 75 boys), aged 1 to <2 years, with VUR grade III or IV randomised to antibiotic prophylaxis (n = 69), endoscopic injection (n = 66) or surveillance (n = 68)

In girls, recurrence rate was 19% on prophylaxis, 23% with endoscopic treatment and 57% on surveillance (p = 0.0002).

In boys, there was no difference between treatment groups

Summary:

In boys - no difference

In girls - prophylaxis: Reduces UTI recurrence + new renal damage. STING: reduces UTI recurrence only

Meta-analysis - Arch dis childhood 2003

Ureteric reimplantation + antibiotics vs antibiotics alone - 60% reduction in febrile UTI

No difference with renal scarring

Circumcision

2005 Meta Analysis - Singh-Grewal

For normal boys, the number-needed-to-treat (NNT) to prevent one UTI is 111. In boys with recurrent UTI or high-grade vesicoureteric reflux, the NNT drops to 11 and 4, respectively

Standard scenario

Patient presents with UTI

Concerns:

1. Protecting renal function

2. Severe sepsis

3. Presence of any surgical modifiable risk factors

Resuscitate with antibiotics

History:

LUTS

Recurrent UTIs

Bladder and bowel dysfunction

Previous renal tract imaging and surgery

Examination:

Sepsis

Abdomen - faecaloma, bladder mass

Spine - occult dysraphism

External genitalia - phimosis, labial fusion

Investigations:

Renal function (U+E)

Check cultures (look for atypical organisms), ensure antibiotics effective

NICE guidelines:

If <6 months or atypical or recurrent

USS KUB + pre + post void (Acute if inpatient)

If >6 months and not atypical or recurrent - no investigation

Proceed to investigate for VUR/Scarring for atypical/recurrent

Best investigation is MCUG + DMSA but only if will tolerate catheter

If potty trained - get MAG3 + Indirect cystogram

Do not do DMSA/MAG3/MCUG when acutely unwell

International reflux society grading - IRS for VUR

Evidence summary for VUR:

Most studies support use of antibiotic prophylaxis in preventing febrile UTI, girls may benefit more than boys, however its benefit in preventing renal scarring is less clear.

Swedish trial - benefit of antibiotics for girls. STING does not reduce new renal damage

Management ladder:

1. Toileting advice:

• Posture on toilet - elevate feet

• Wiping front to back

• Double voiding

• Timed voiding (withholding)

• Manage constipation

2. Increase fluid intake

3. D Mannose

4. Prophylactic antibiotics (or change if already on)

5. STING (investigate for reflux if not done so) offer circumcision

6. Urodynamics - then treat bladder dysfunction

Special scenario - Posterior urethritis

History

Terminal haematuria

Previous catheters etc

Painful or not? Should have dysuria

Systemic symptoms

Examination

Abdominal masses

Foreskin

Investigation

USS

Bloods

Get uroflow

Management

Reassure - Self limiting

No evidence for medical treatment - can use ranitidine

If persistent at 3 months - cystoscopy to confirm and rule out stricture

At 6 months do triamcinolone instillation

If stricture - dilatations, may need steroid injection

References

Essentials of Pediatric Urology, 3rd edition, 2022, Chapter 4 Urinary Tract infection

Essentials of Pediatric Urology, 3rd edition, 2022, Chapter 5 Vesicoureteral Reflux

Urinary tract infection in under 16s: diagnosis and management

NICE guideline [NG224]Published: 27 July 2022

https://www.nice.org.uk/guidance/ng224

Yap TL, Chen Y, Nah SA, Ong CC, Jacobsen A, Low Y. STING versus HIT technique of endoscopic treatment for vesicoureteral reflux: A systematic review and meta-analysis. J Pediatr Surg. 2016 Dec;51(12):2015-2020. doi: 10.1016/j.jpedsurg.2016.09.028. Epub 2016 Sep 16. PMID: 27773360.

Murphy M, Scanlon L, Elamin M, O'Connor C, Mayer N, Brady C, Hennessey D. The STING in the tale of Teflon®: Delayed ureteric obstruction after subureteric transurethral injection with polytetrafluoroethylene paste for vesicoureteral reflux. Surgeon. 2024 Feb 22:S1479-666X(24)00016-7. doi: 10.1016/j.surge.2024.02.001. Epub ahead of print. PMID: 38395646.

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Damm T, Mathews R. The RiVUR Study Outcomes and Implications on the Management of Vesicoureteral Reflux. Arch Nephrol Ren Stud. 2022;2(1):1-5. PMID: 35928985; PMCID: PMC9348554.

Brandström P, Jodal U, Sillén U, Hansson S. The Swedish reflux trial: review of a randomized, controlled trial in children with dilating vesicoureteral reflux. J Pediatr Urol. 2011 Dec;7(6):594-600. doi: 10.1016/j.jpurol.2011.05.006. Epub 2011 Jul 31. PMID: 21807562.

Wheeler D, Vimalachandra D, Hodson EM, Roy LP, Smith G, Craig JC. Antibiotics and surgery for vesicoureteric reflux: a meta-analysis of randomised controlled trials. Arch Dis Child. 2003 Aug;88(8):688-94. doi: 10.1136/adc.88.8.688. PMID: 12876164; PMCID: PMC1719586.

Singh-Grewal D, Macdessi J, Craig J. Circumcision for the prevention of urinary tract infection in boys: a systematic review of randomised trials and observational studies. Arch Dis Child. 2005 Aug;90(8):853-8. doi: 10.1136/adc.2004.049353. Epub 2005 May 12. PMID: 15890696; PMCID: PMC1720543.