Vesicoureteral Reflux

KARUNAN KANNAMPOYILIL

Last updated;2002

WHAT is

●Vesicoureteral reflux (VUR) or the retrograde flow of urine from the bladder into the ureter, is an anatomic and functional disorder with potentially serious consequences.

●Primary Reflux & Secondary Reflux

P&S VUR●Primary reflux is VUR in an otherwise normally

functioning lower urinary tract(UT), ●Secondary reflux is VUR that is associated

with or caused by an

obstructed or poorly functioning lower UT, such as that observed with

Posterior urethral valves (PUV) or

A neurogenic bladder.

UreteroVesical Junction (UVJ)

●In both conditions, the UVJ fails to function

as a One-way valve, giving lower urinary tract bacteria access to the normally sterile upper tracts.

●Although VUR has been recognized as an anatomic phenomenon for centuries, not until relatively recently were the substantial morbidity and mortality associated with the condition recognized.

Early studies

●correlation between reflux and chronic pyelonephritis in paraplegic individuals

●UTI, reflux, and CPN●Suggested that prevention of VUR ●may result in reduced prevalence of renal

complications.

The objectives in the current Rx ●The first goal is the prevention of episodes of AcPN

associated morbidity and mortality.

●The second goal is to prevent the scarring of the kidney associated with VUR (Reflux nephropathy), which increases the risk of hypertension and renal failure in children and adults with VUR.

●Advances in medical and surgical treatment of children with VUR are now resulting in measurable decreases in the prevalence of Reflux Nephropathy and its sequelae: HTN, RF, ESKD.

Pathophysiology●After entering the bladder through the

muscular hiatus, ●the normal distal ureter passes through

a submucosal tunnel ●before opening into the bladder lumen

via the ureteral orifice.

length of the submucosal tunnel

●If the length of the submucosal tunnel or its muscular backing is inadequate,

●the valve mechanism is incompetent, resulting in reflux.

Basis for almost all surgery

●Careful anatomic measurements suggest that the ratio of tunnel length to ureteral diameter must be at least 5:1 to prevent reflux.

●This fundamental observation is the basis for almost all surgical procedures to correct the disorder.

Beyond the fetal stage, anatomic reflux alone rarely produces renal damage.

●Experiments in pigs have demonstrated renal scarring in sterile refluxing systems, and while the kidneys may display scarring and/

●or dysplasia in some patients with prenatally identified and presumably sterile reflux,

●the overwhelming majority of data implicate ascending infection and pyelonephritis as the essential causes of reflux nephropathy.

Large studies have repeatedly

demonstrated a close correlation btnthe frequency of UTI &severity of RNP in VUR.

the "big bang" effect.●One episode of

pyelonephritis produce Scarring, especially in very young.

●Ransley and Risdon named this condition the "big bang" effect.

Intrarenal Reflux●Most scarring tends to occur at the renal poles,

●Where the anatomy of the renal papillae permits backflow of urine into the collecting ducts.

●This phenomenon is referred to as intrarenal reflux

●& gives pathogenic bacteria access to the renal tubules.

Renal failure

●Subsequent cascade of inflammation, ●Release of superoxide & other

mediators, ●Results in local tissue ischemia &

fibrosis. ●When enough renal parenchyma is

affected,

●HTN,RF can result.

Why little kidneys > proneThe reason kidneys of children are so susceptible to damage is Not clear, But it may be caused by reduced levels of renal superoxide dismutase in children.

Frequency

●In the US:

●Overall prevalence of VUR is unknown,

●Rates of 1-2% ?

Internationally

●Many large studies have been performed in Europe, where prevalence is estimated to be similar to that in the United States.

●Disease frequency in other parts of the world is not well described.

VUR&UTI

●Prevalence of VUR is quite high ●children with UTIs-15-70%. ●Among infants Antenatally

identified to have hydronephrosis on USG

●1/3 have VUR Postnatally.

Genetic factors,●Clearly is influenced by genetic factors,●specific modes of inheritance not identified. ●Siblings of VUR have a 25-33% risk for VUR,●While offspring of parents with reflux have a 66%

incidence (higher in female offspring than male offspring).

●Even when asymptomatic, these siblings and offspring can have high-grade reflux and often have renal scarring at evaluation.

●As a result, aggressive screening of siblings and offspring of patients with reflux is advocated to identify these children before they progress to renal damage.

Race●Reflux is more common in white children than in those of other races.

●VUR is less common in black children, ●Since little is known about the specific

genetic linkage of VUR and the wide variation of genes with intermarriage, excluding any group from evaluation is difficult.

Sex●UTIs are more common in females, ●as one might expect given the anatomic

differences. ●This leads to greater screening and,

therefore, diagnosis of VUR in females.●However, among all children with UTI,

boys are more likely to have VUR than girls (29%vs 14%).

Age●VUR is more common among infants and

resolves progressively in a substantial proportion of children;

●thus, prevalence decreases as age increases.

●One study demonstrated prevalence of ●70% younger than 1Yr,●25% in 4Yr, 15% in 12Yr & ●5.2% in adult presenting with UTI.

History of●VUR present in 1 of 2 distinct

groups. ●1st presents with hydronephrosis,

often identified antenatally by ultrasound.

●These children typically progress through evaluation and treatment in the absence of clinical illness.

The second group●presents with clinical UTI. ●Even for experienced pediatricians,

the diagnosis of UTI in children can be difficult.ononspecific SNS&SMSoAs failure to thrive, with or without fever. ovomiting, diarrhea, anorexia, and lethargy.oOlder children may report voiding

symptoms or abdominal pain.

PN in young children●With vague abdominal discomfort

rather than with the classic flank pain and tenderness observed in adults.

●The presence of fever, while highly suggestive ofPN, is not reliable enough to lead to the diagnosis.

Even today?!!!,●Children occasionally

present with advanced RNP,●Manifesting as headaches or ●CCF from untreated HTN, ●or with uremia of renal

failure

A small group of children●without evidence of UTI present with

symptoms of sterile reflux, ●which can include flank or abdominal

pain before or during voiding, ●as well as double voiding or incomplete

emptying ●resulting from delayed drainage of

urine out of the upper tracts.

HTN&RF

●RNP may be the most common cause of childhood HTN.

●Presence of hypertension correlates well with the degree of renal scarring, especially when scarring is bilateral.

The mechanism

●The mechanism is thought to be elevated renin levels produced by damaged renal tissues.

●Although not all scarred kidneys in hypertensive children produce excess renin,

●Resection of renal units in cases where unilateral renal vein renin levels are elevated substantially (ratio >1.5) can result in resolution of hypertension.

Physical EX●on physical examination suggest VUR

or UTI. ●Fever, flank or abd; tenderness, ●or an enlarged palpable kidney .●Intact foreskin in male infants should

raise the index of suspicion. ●UTI and PN are substantially higher in

uncircumcised boys during the 1st yr.

In the absence●Of reliable historical or ●Physical findings, ●Diagnosis is dependent ●On laboratory testing ●& imaging.

Lab Studies●Diagnosis of UTI is dependent on

obtaining accurate urine cultures.ostandard urine specimens by suprapubic

aspiration.oAny growth considered significant. oIf no samples are obtained by other means. oGrowth of more than 100,000 CFU/mL is a

significant on a midstream-voided urine

cystitis from pyelonephritis.

●Although the WBC count, ●serum levels of C-reactive protein,●and other blood tests ●used to assist with the diagnosis, ●no laboratory tests can reliably

distinguish cystitis from pyelonephritis.●CBC count can assist in tracking the

response to treatment

Imaging Studies●Imaging is the basis of diagnosis and Mx of

VUR. ●USG& voiding cystourethrogram

(VCUG),

When,how,what&not●Imaging after a first UTI is indicated in

all children < 5 years with UTI, ●Any age with UTI, ●Antenatally identified hydronephrosis

should be evaluated Postnatally. ●USG during the first 3 days of life may

have a high rate of false-negative results

●because of Relative dehydration .

VCUG●The STD criterion in

diagnosis of VUR ●Provides precise

anatomic detail & allows Grading of the reflux.

The International Classification

oGrade I - Reflux into nondilated ureter oGrade II - R into renal pelvis and calyces without

dilation oGrade III - R with mild-to-moderate dilation and

minimal blunting of fornices oGrade IV - R with moderate ureteral tortuosity and

dilation of pelvis and calyces oGrade V - R with gross dilation of ureter, pelvis,

and calyces, loss of papillary impressions, and ureteral tortuosity

VCUG●In general, ●The VCUG after fully recovered from the UTI.●Performance of the study during an episode of acute

cystitis can result in overestimation of the grade of reflux because of paralysis and laxity of the ureteral musculature by bacterial endotoxin.

●Conversely, some children demonstrate reflux only during an episode of cystitis.

●useful imaging of the urethra in males for evaluation of PUV.

●Standard VCUG is recommended as the initial study in boys.

Nuclear cystogram with instillation of technetium TC 99m●into the bladder and observation with a gamma camera

is a highly sensitive test for VUR.oAdvantages include substantially lower radiation doses to

the patient and potential for increased sensitivity because of the ability to conduct prolonged periods of observation.

oDisadvantages consist primarily of the poor anatomic detail, especially of the male urethra.

oGrade 1 reflux is poorly detected by this study. Grading by nuclear cystography is limited to mild, moderate, and severe grades.

oOne approach is to use the nuclear cystogram as the initial screening test in girls and then perform standard VCUG when VUR is observed.

USG Kidneys●The primary purpose ●Assess size, parenchymal thickness, and

collecting system dilation.

Despite so many advantages, oA normal USG does not exclude VUR. oOnly the VCUG or onuclear cystogram ocan reliably exclude VUR.

DMSA

●The primary radiopharmaceutical used with renal scintigraphy in the setting of pyelonephritis and VUR is technetium TC 99m–labeled dimercaptosuccinic acid (DMSA).

Cold Spots on Imaging●This agent is taken up rapidly by

proximal renal tubular cells and is an excellent indicator of functioning renal parenchyma.

●Areas of acute inflammation or scarring do not take up the radiopharmaceutical and are revealed as cold spots on imaging.

DMSA●As a diagnostic tool during

suspected episodes of acute PN.

●However, the indication is to identify and monitor renal scarring.

SPECT

●Single-photon emission computed tomography (SPECT)

●Allows for higher resolution and more accuracy in detection of renal scarring.

Urodynamic studies●Reveal functional abn of lower urinary tract.

oSuch testing is most important in patients in whom secondary reflux is suspected,

oSuch as patients with spina bifida or

oVCUG is suggestive of residual PUVoSince Antireflux surgery is less successful

in cases with secondary reflux, oIdentifying such cases before operative

intervention is critical.

Cystometrogram (CMG),●The basic test is the cystometrogram (CMG),

during which a catheter with an intrinsic or attached manometer is placed in the bladder and the bladder is filled slowly with fluid while its internal pressure is recorded.

●The CMG gives information about bladder capacity and leak point, pressures at various stages of filling, and the presence and frequency of uninhibited (involuntary) bladder contractions.

Detrusor instability●Detrusor instability is a common finding among

children with reflux, and, in some cases, treatment with anticholinergic medication has resulted in resolution of the reflux.

●The technical difficulty of performing urodynamic studies in small children, especially infants, is a significant obstacle.

Procedures

●Historically, cystoscopy was considered to be a basic element of evaluation for VUR.

●The position and shape of the ureteral orifices were thought to correlate with the grade and prognosis.

●Subsequent data have demonstrated that cystoscopic observations do not significantly contribute to the radiographic findings.

Cystoscopy

●Cystoscopy is sometimes performed at the time of ureteral reimplant surgery

●to identify additional anatomic abnormalities,

●such as ureteral duplication ●and ureteral ectopia.

Histologic Findings

●Pathologic evaluation does not play a significant role in the diagnosis of VUR.

Medical Care-AIMS/options

●To prevent kidney infection, ●kidney damage, and ●the complications of kidney damage. ●Treatment options ●medical therapy, ●surgical therapy, and●surveillance.

RD Walker ●(1) spontaneous resolution of VUR is common in

young children but is less common as puberty approaches,

●(2) severe reflux is unlikely to resolve spontaneously,

●(3) sterile reflux, in general, does not result in reflux nephropathy,

●(4) long-term antibiotic prophylaxis in children is safe, and

●(5) surgery to correct VUR is highly successful in experienced hands.

Surveillance●Surveillance has become less common as the

safety of antibiotic prophylaxis has been established and

●as the risks of kidney damage because of delayed diagnosis and

●the treatment of UTI have become better appreciated.

●Surveillance is still a reasonable option in older children with reflux,

●however, especially boys who have not had UTIs.

Initial treatment

●Supportive care and ●Prompt administration of appropriate antibiotics.

opreventing scar formation in kidneys with pyelonephritis.

oAnimal studies have demonstrated that permanent renal damage occurs if antibiotics are not started within 72 hours,

oalthough other studies indicate an even shorter window of opportunity.

oFor this reason, clinicians must maintain a high index of suspicion for UTI in children.

mainstay of medical management

●is antibiotic prophylaxis. ●Once a child has been treated for UTI or has

had an abnormality identified on imaging, start the child on prophylaxis.

●In general, antibiotics are continued until anatomic abnormalities,

●such as VUR, are excluded or resolve with or without intervention or

●until the child grows old enough that prophylaxis is no longer necessary.

Virtually all children●with a new diagnosis of grade I-IV reflux,●& Some with grade V, ●Given a trial of medical treatment. ●This consists of antibiotics dosed at one

fourth of the therapeutic dosage and●Regular follow-up care and imaging. ●A typical routine includes renal ultrasound

and●VCUG or●Nuclear cystogram every 12-18 months.

follow-up care●Since a substantial number of children experience spontaneous

resolution of VUR (50-85% of cases with grade I-III VUR), ●medical treatment spares this group the morbidity of surgery while

protecting the kidneys from further damage. ●Once follow-up imaging demonstrates resolution of VUR, antibiotics

are discontinued. ●The importance of conscientious follow-up care during conservative

treatment cannot be overemphasized.●Lack of compliance with medications or surveillance imaging

continues to result in reflux nephropathy and renal failure in children in whom these outcomes were completely preventable.

boys approach puberty

●In boys with persistent VUR who have not had recurrent UTIs, antibiotics are often discontinued as the boys approach puberty.

●However, because of concerns about future pregnancies, surgery is usually recommended in girls approaching puberty who have persistent VUR .

●Bladder and bowel management for dysfunctional elimination are as follows

Anticholinergic medication●Anticholinergic medication, in conjunction with timed voiding, may

improve symptoms of dysfunctional voiding and reduces the risk of infection.

●Anticholinergic agents should be used in select patients so as not to compound the problems of incomplete bladder emptying or worsening constipation.

●A few of these patients benefit from some form of bladder training to achieve balanced, low-pressure voiding with coordinated relaxation of the external sphincter and pelvic floor.

●In children with primary bowel elimination problem, treatment with enemas, dietary changes, and stool bulking agents, in coordination with a pediatric gastroenterologist, is critical for success.

Diet●Children with frequent UTIs often have

concurrent problems with constipation and poor bowel habits.

●Institution of a bowel program in these children can reduce the frequency of infection.

●High-fiber diets combined with a stool softener, such as mineral oil (5 cc/d),

●can improve bowel function and reduce colonic and rectal dilation.

Activity●Children with VUR can engage in normal

activity. ●Toilet hygiene, especially proper wiping

technique in girls, ●should be taught to children of appropriate

age to reduce the frequency of UTI.

Drug Category●Antibiotics -- These are used for maintenance of

sterile urine. ●Antibiotic agents used for prophylaxis in children

with VUR are chosen for their efficacy in the urinary tract, safety, and tolerability.

●The typical dose is one fourth of the therapeutic dose.

●They are usually administered as suspensions once daily,

●typically in the evening to maximize overnight drug levels in the bladder.

Surgical Care●In the final analysis, the decision to

proceed to surgery is often made on philosophical as much as scientific grounds,

●and the medical, social, and emotional needs of the patient and the family need to be considered.

Indications for surgery●(1) breakthrough febrile UTIs despite adequate antibiotic

prophylaxis, ●(2) severe reflux (grade V or bilateral grade IV) that is

unlikely to resolve spontaneously, especially if renal scarring is present,

●(3) mild or moderate reflux in females that persists as the patient approaches puberty, despite several years of observation,

●(4) poor compliance with medications or surveillance programs,

●and (5) poor renal growth or function or appearance of new scars.

Principles

●Virtually all operations designed to treat VUR involve reconstruction of the UVJ

●to create a lengthened submucosal tunnel for the ureter,

●which functions as a one-way valve as the bladder fills.

●Dozens of procedures have been described.

Politano-Leadbetter procedure●Developed in the 1950s, prototype intravesical operation ●The ureter is dissected completely free of its attachments

and ●passed through a new muscular hiatus created higher on

the bladder wall. ●The ureter is then passed down through a submucosal

tunnel, ●and the orifice is sutured to the mucosa at its original

meatal position.●Success rate of 97-99%.

Cohen cross-trigonal technique●An evolution of the PL ●most popular repair performed today.●the original muscular hiatus is used, ●but the ureter is dissected from its attachments

and pulled across the trigone through a submucosal tunnel,

●and the meatus is sutured into a new position at the end of the tunnel.

●Reported rates of success range from 97-99% with this technique as well.

Lich-Gregoire extravesical approach ●Developed concurrently in Europe and the United States, the Lich-

Gregoire repair approaches the bladder via the retroperitoneum. ●The ureter is dissected from the detrusor, but the orifice is left intact. ●A narrow furrow in the detrusor then is created, down to but not

disrupting the mucosa, extending cephalad from the ureteral orifice. ●The distal ureter is then laid into this furrow and the detrusor closed

over it.●Although early American results were disappointing, further

experience and modifications have demonstrated success rates comparable to the standard intravesical techniques.

●The extravesical approach has a significant frequency (16%) of postoperative urinary retention or incomplete emptying, which resolves spontaneously.

extravesical approach

●The was developed in an effort to avoid the time and morbidity associated with the cystotomy and ureteral anastomosis required for intravesical repair.

●It is particularly useful in patients with unilateral reflux.

endoscopic treatment of VUR

●Experimental, holds great promise because it would allow treatment of the underlying anatomic defect while avoiding the morbidity of open surgery.oThe technique involves injection of a bulking

substance into the muscular posterior wall of the UVJ.

oThe resulting swelling compresses the ureteral lumen, preventing reflux out of the bladder.

Persistent reflux after surgery●Modern series consistently report success rates greater

than 95% for antireflux surgery.●In cases in which reflux persists postoperatively,

observation with continued antibiotic prophylaxis is indicated.

●A very high percentage of patients in whom surgery has failed have voiding dysfunction,

●thus urodynamic evaluation should be considered in these patients, especially if reoperation is considered.

●Even so, a substantial majority of patients with reflux at the first postoperative study have complete resolution at the 1-year follow-up point.

MortalityMorbidity●With isolated VUR is uncommon●Morbidity is substantial, ●both from the A/c inf process ●From the sequelae of RN.

Changes in renal function

Decreases in urine-concentrating ability (proportional to the degree of reflux)

& in GFR(proportional to the degree of renal scarring)

have been measured in children with VUR.

Decreased renal and somatic growth:

●Although renal growth assessment in children is difficult because of imaging variability,

●several studies have documented smaller kidneys in children with reflux and recurrent infections.

●Surgery may improve growth rates, ●but in severely scarred kidneys, ●stunting often persists.

properly treated children with VUR

●Although some studies have suggested that somatic growth is affected negatively in refluxing children and while children with end-stage renal disease clearly have decreased growth rates,

●more recent data have shown that carefully monitored, properly treated children with VUR have growth rates within normal ranges.

UTI may cause reflux●The possibility that UTI may cause reflux

has also been investigated. ●Indeed, a subset of patients has been

identified in whom reflux was detectable only during an episode of cystitis.

However,●most authorities think that UTI and reflux

are independent variables and that rates of VUR are higher in children with UTI because these children are actively screened for reflux.

●The cause-and-effect picture is even less clear in children with secondary reflux.

bladder outlet obstruction and neurogenic bladder.

●Little doubt exists that rates of reflux are increased in the setting of congenital bladder outlet obstruction and neurogenic bladder.

●More than 50% of boys with posterior urethral valves have VUR.

●Similar results were seen in a series of children undergoing urodynamic studies for neurogenic bladder

high-pressure voiding and VUR●That dysfunctional voiding, with its inherent

increase in intravesical pressure, can also result in reflux, even in otherwise healthy children, is becoming increasingly clear.

●Uninhibited bladder contractions, often associated with contraction of the voluntarily controlled external urinary sphincter to prevent wetting, increase intravesical pressure.

●The combination of high-pressure voiding and VUR increases the risk of pyelonephritis beyond that of the child with low-pressure reflux.

voiding dysfunction and obstruction

●Confounding all of these data is the fact that urodynamic studies on children are difficult to perform and evaluate; this is true especially with infants, in whom normal reference data are sparse.

●Whether VUR observed in association with voiding dysfunction and obstruction is a direct result of that dysfunction or simply a component of a grossly abnormal urinary tract is not known.

●A unique and complex group of children presents with dysfunctional elimination, which consists of a symptom complex heralded by infection, severe constipation, and daytime wetting.

●Despite the primary urinary tract presentation, the primary focus should be in the management of constipation and bowel habits.

●A subset of these children have infrequent voiding and incomplete bladder emptying, which further increases the likelihood of UTI.

DD

●Antenatal Hydronephrosis Myelodysplasia and Neurogenic Bladder Dysfunction

PUV UPJ Obstruction Urethral Anomalies and Urethral Prolapse

Urinary Tract Infection Voiding Dysfunction

Prognosis:Primary reflux●Studies comparing medical Mx Vs surgical Mx primary

VUR ●both have excellent long-term outcomes if surveillance is

conscientious and compliance is good.●Rates of RN are similar in the 2 groups, ●surgically Rx have a lower prevalence of pyelonephritis.●Recent studies of adults with childhood reflux and

children, the prevalence of RN lower than in historical series.

●These results seem to validate current management strategies.

Secondary reflux

●Treatment of children with secondary reflux continues to pose challenges to pediatricians and urologists.

●A clear understanding of bladder function is essential.

●Other children have complex combinations of reflux, obstruction, and bladder and renal dysfunction that require a concerted multidisciplinary approach to achieve the maximum potential benefit of therapy.