Retrograde flow of urine from the bladder towards the kidneys
Aetiology
The result of an inadequate submucosal ureteric tunnel, leading to a failure of the VUJ’s passive valve mechanism
- Normal VUJ provides a valvular mechanism preventing retrograde flow of urine, even during increased voiding pressures
- Flap-valve mechanism whereby the intramural and submucosal ureter distal ureter are compressed by the detrusor muscle during bladder filling
- During voiding, elongation of intravesical ureter within Waldeyer’s sheath reinforces this
- In children with primary VUR, the UO is characteristically located more laterally on the bladder base (think duplex)
- Resulting shorter intramural ureter, with deficient flap valve mechanism
- Both the relative and absolute length of the submucosal tunnel tend to increase with age -> often spontaneous resolution
Classification
Primary VUR
- Anatomical abnormality of the VUJ – shortened intra-mural ureter with weakened flap-valve mechanism
Secondary VUR
- Associated with abnormal bladder function and elevated intravesical pressure – e.g. neuropathic bladder and posterior urethral valve
- May resolve with treatment of underlying increased intravesical pressures
Voiding dysfunction
- Clear that there is a relationship between once thought primary VUR and non neuropathic voiding dysfunction – two way relationship between reflux and voiding dysfunction
Incidence and genetics
- About 1 % of general population
- Definite familial component – 1/3 of siblings will have VUR, and over 50 % of offspring of those with VUR
- Over 30 % of children < 5 being investigated for UTI
- 3 – 4 x as common in girls
- Girls tend to present clinically with UTI a bit later, boys more often detected incidentally and antenatally
- Girls tend to be lower grade, boys higher grade
- Girls more often associated with functional issues – bladder and bowel dysfunction
Pathophysiology / complications
Reflux of sterile urine at normal voiding pressures doesn’t seem to cause renal scarring.
In most cases, development of renal parenchymal scarring is due to the reflux of infected urine from the bladder.
The risk of renal scarring is maximal in infancy and childhood.
Maximal renal scarring occurs after first episode of pyelonephritis.
The risk of infection causing renal scarring seems to decrease after 4 years.
There are likely differences between acquired scars due to infection and reflux, and ‘congenital’ scarring associated with dysplasia or hypoplasia.
Scarring is more likely to occur at the poles and with higher grade reflux and more frequent infection.
Scarred renal parenchyma becomes non functioning, leading to reflux nephropathy and:
- Chronic kidney disease in childhood and adulthood
- Risk of end stage renal disease
- Hypertension – in childhood and into adulthood
Grading of VUR
Diagnosis and work-up
Ultrasound – often false negatives / cannot diagnose or exclude VUR – but good at looking at parenchyma, bladder function
MCUG – gold standard – ensure antibiotic cover or clear urine at time
DMSA – demonstration of renal scarring and split renal functioning – ?influencing decision making
?Best screening for siblings – USS not perfect but less invasive than MCUG
Serum creatinine, urine culture, microscopy for proteinuria, and history/exam focussed on bladder bowel dysfunction.
Management
Principles of managing VUR:
- Prevent urinary tract infection
- Protect renal function
- Manage symptoms
- Treat associated correctible causes (bladder bowel dysfunction)
Aim – allow for the possibility of spontaneous resolution of VUR while preventing UTI associated scarring in the process.
Avoid algorithmic treatment and manage flexibly and individually for each child
Management options:
- Conservative / medical management
- Endoscopic management
- Surgical management / re-implantation
Conservative / medical management
- Antibiotic prophylaxis – Keflex 10 mg/kg daily ; trimethoprim 2 mg/kg daily ; bactrim ¼ mL/kg/day
- Reduces the rate of febrile UTI – evidence for reducing scarring, particularly in boys, less clear (probably doesn’t affect scarring)
- For how long – ?until out of nappies
- ?Do grade 1 – 2 need antibiotic prophylaxis
- Aggressive management of bladder and bowel dysfunction (seems to be the key factor)
- Circumcision for boys
- Consider and treat other causes (neurogenic bladder, valve, bladder bowel dysfunction etc)
Endoscopic management
- Injection of agent submucosally beneath the intramural ureter – elevated the UO and distal ureter, increasing coaptation and prevent reflux whilst allowing antegrade flow
- Most commonly used is Deflux – dextranomer/hyaluronic acid combination
- Success rate of 80 % or more (recurrence rate 20 %) for normal bladders without functional issues
- Probably best used for grade 3 – 4 with breakthrough UTIs
- Attractive option for either avoiding long term prophylactic antibiotics or avoiding open surgery
- Injection is at 6 o’clock of UO (STING), or if scope can advanced into distal ureter then transureteric (HIT) preferred – aim to create a bulge under ureter with slit-like UO
- STING – sub ureteric Teflon/transurethral injection
- HIT – hydrodistension implantation technique (double HIT – proximal and distal)
- Risks of bleeding and obstruction
Open surgical management:
Indications for surgical repair:
- Recurrent febrile UTIs despite antibiotic prophylaxis
- Progressive renal scarring (usually with recurrent UTIs)
- Non compliance with medical/conservative management
- ?Grade 4-5 reflux with renal abnormality
- Parental preference
Principles of successful surgery:
- All procedures aim to lengthen the intra-mural ureter with a submucosal tunnel
- Submucosal tunnel should be at least 5 x the width of the ureter
- Preserve the vascularity of the distal ureter
- Assure a straight and non-twisted passage both extravesically and intramurally
Cohen cross-trigonal reimplant
- Most commonly performed / procedure of choice
- Suitable for all grades
- Very successful – 97 %
- Low rates of post-operative obstruction
- Can be performed bilaterally. May be extremely difficult ureteroscopy in later years.
Politano-Leadbetter
- Intravesical – new hiatus created superiorly to original UO
- Higher rates of post-operative ureteric obstruction
- May be preferred for megaureter
- Better for endoscopic instrumentation of ureters in future
Lich-Gregoir extravesical
- May be done laparoscopically or robotically
- Less haematuria and post-operative discomfort
- Potentially higher rates of transient urinary retention and bladder dysfunction
Practice point – Cohen cross-trigonal nice operation in toddler with mostly intra-peritoneal bladder, but very difficult in older children as bladder descends – extra-vesical Lich-Gregoir preferred from about age 6 on.
Surgical complications:
- Ureteric obstruction 1-2 %
- Bladder dysfunction
- Bleeding / haematuria
- Contralateral reflux – up to 15 % on follow up MCUG – usually settles without intervention
- Further UTI
- More common in girls, esp with bladder and bowel dysfunction
- Bowel injury
Follow-up
- Annual urinalysis for proteinuria + blood pressure checks
- Post-operative MCUG or DMSA – surgeon preference – most largely prefer symptomatic follow up
- Some patients develop chronic kidney disease and ESRF
- Continue to work on bladder and bowel dysfunction
EAU table:
