UTI and VURPediatric GU Review

UCSD Pediatric UrologyGeorge Chiang MDSara Marietti MD

Outlined from The Kelalis-King-Belman Textbook of Clinical Pediatric Urology 2007

(not for reproduction, distribution, or sale without consent)

UTI

• Second most common bacterial infection in children• In the first year of life, uncircumcised boys more

susceptible to bacteriuria than girls (2.5:1)• After year one, females are more susceptible than

males (20:1)• Infants with symptomatic infections have a 26%

chance of recurrence, usually within the next 3 mo

UTI

• Risk of UTI in susceptible children persists as they get older, and increases risk of bacteriuria of pregnancy

• Study showed that 68% of those with bacteriuria of childhood had bacteriuria of pregnancy, compared to 26% of controls with no childhood bacteriuria

• Gillenwater, NEJM. 1979

Etiology

• E. coli is most common organism (85%)• E. coli, Klebsiella, Proteus, Psuedomonas, and

enterococci represent 95% of all infections• High frequency of proteus in older uncircumcised

boys• Higher likelihood of staphylococcal infection in

adolescent girls• Greater frequency of E.coli uti in neonatal boys than

girls• Winberg, Acta Ped Scand, 1974.

Virulence Factors

• Endotoxin – lipopolysaccharide present in bacterium’s cell wall, initiates acute inflammatory response, this response may cause scarring

• K-capsular antigen – increase the bacterium’s resistance to phagocytosis by polymorphonuclear leukocytes

Virulence Factors

• Hemolysin – digests cells surrounding the site of bacterial adherence, thus aiding in invasion

• Cell surface adhesions molecules (fimbria) – appendages on E.coli that help to adhere to human epithelial cells

P-Fimbriae

• Bind to specific carbohydrate moiety on the uroepithelial cell surface

• Allow bacteria to ascend up the urinary tract• Important factor in non-reflux pyelo• Protective adhesins such as Tamm-Horsfall,

can competitively bind to fimbriae thus prohibiting binding to the uroepithelium

Risk Factors for UTI

• Perineal colonization by intestinal flora is source of most infections

• Females – colonization of the introitus• Males – colonization of the preputial epithelium• This colonization may explain why infant boys

(uncircumcised) have higher rates of uti than infant girls despite longer urethras

• Risk of pyelo 10x greater in boys not circumcised at birth compared to circumcised boys

• Wiswell. J of Pediatrics. 1988

Risk Factors for UTI

• Most explain the higher prevalence of female to male UTI’s (past the age of 12 mo) by the short length of the urethra

• No evidence to suggest improper wiping or bubble baths lead to increased infections

Risk Factors for UTI

• Dysfunctional voiding is associated with increased risk of infections, management of the dysfuctional voiding can decrease UTI incidence

• One study found 50% of girls with UTI between age 3-5 were dysfunctional voiders

• Fecal elimination is a factor also, must treat constipation

• Hellstrom. Arch Dis Children. 1991.

Risk Factors for UTI

• Presence of VUR increases chance that organism will access the renal perenchyma

• Reflux allows those organisms that do not have specific virulence factors to gain access to the upper tract

• Thus, LESS virulent organisms are more often isolated in reflux pyelonephritis

• However, the majority of cases of acute pyelo in kids are not associated with reflux

Renal Scarring

• Renal scarring in a/w VUR occurs only with infection, not sterile urine

• Studies found that scarring occurred with reflux of sterile urine only when obstruction was present (PUV, Hinman’s Syndrome)

• The intermittent high pressure of voiding is not enough to cause scarring

• Ransley. Br J Radiol. 1988

Renal Scarring

• Related to number of pyelonephritic episodes• Severity of scarring is associated with severity of VUR• Bacteria attach to uroepithelium and start

inflammatory response• Granulocytes aggregate within capillaries and

occlude vessels leading to ischemia• Reperfusion of the ischemic tissue leads to

generation of oxygen radicals which are toxic to bacteria and renal tissue

Congenital Reflux Nephropathy

• Severe reflux may be a/w significant renal dysplasia from abnormal induction of metanephric blastema by ureteral bud

• More often a/w small kidneys or global loss of perenchyma vs focal defects from pyelo scars

• Most have severe VUR (III or higher), detected prenatally, and are male

• DMSA scans done prior to infection show functional abnormalities in 20-60%

Consequences of Scar

• Hypertension • More common in severe bilateral scarring• With longer follow up, percentage of kids with

hypertension increases• One study found 38% with 34 years of follow-

up• Jacobson. Br Med Journal. 1989.

Renal Insufficiency

• 5-10% of kids on dialysis, from reflux nephropathy

• Studies show that kids who stay infection free with their VUR usually do not have progressive renal damage

• Most severe damage from infection usually occurs early in life

Diagnosis of UTI

• Pyuria on UA not 100% reliable• LE 88-95% sensitive for detection of pyuria• Nitrite 30-45% sensitive, 98% specific• Combined 78-92% sensitive, 60-98% specific• Should diagnose by urine culture

Diagnosis of UTI

• >100,000 colonies in voided specimen • >10,000 colonies in catheterized or

suprapubic aspirate• Bagged specimen helpful if negative

Evaluation of Children with UTI

• Varies widely• High recurrence rate within one year of first infection

(30% in girls, 15% in boys)• About 1/3 of those with UTI’s will have reflux• Significant renal scarring can occur after 1

documented episode of pyelonephritis• Who do you evaluate? All kids less than 5 with

culture documented UTI, all girls with recurrent or febrile infections (Gil Rushton, .M.D.)

Bottom Up Approach

• Goal is to identify all reflux• Cystogram (VCUG or radionuclide)• Ultrasound to evaluate the upper tract• Based on caveat that all kids with reflux need

treatment

Bottom Up Approach

• VCUG very helpful to evaluate male urethra, and better anatomic detail

• Radionuclide cystogram has less radiation exposure, but VCUG starting to minimize exposure

• Both require catheterization• Indirect radionuclide cystogram has been

introduced, but it misses up to 2/3 of refluxing ureters

Bottom Up Approach

• Some recommend waiting 4-6 weeks after infection resolves, so that mild transient reflux from inflammation is not picked up

• Others believe that this is very rare• Others believe that any reflux is meaningful,

especially during infection and recommend imaging after sx resolve and ucx is sterile

• No role for routine cystoscopy

Bottom Up Approach

• Upper tract imaging timing and modality also varies from place to place

• Some recommend US to evaluate for hydro or renal structural abnormalities

• However, yield after first UTI is low• Less than 1% have obstruction requiring

intervention• Hoberman. NEJM. 2003.

Bottom Up Approach

• Ultrasound is not great at detecting scarring• DMSA scan is best to detect scar and acute

pyelonephritis• Clinical parameters have low sensitivity in

detecting pyelonephritis (CRP, ESR, WBC count and fever)

• DMSA is test of choice to demonstrate pyelonephritis

Top Down Approach

• Focus is on renal status, than on presence of VUR• Goal is to identify clinically significant VUR, those

patients at risk for renal scarring• Begins with the DMSA scan• VCUG only for those with abnormal DMSA or

recurrent UTI’s• Attempt to avoid treating “clinically insignificant”

reflux and decrease number of VCUG’s

Treatment of UTI

• Cystitis – optimal duration is controversial, 3-5 day po antibiotic, if < 5 should continue prophylactic antibiotic until radiologic eval completed

• Pyelonephritis – Treat quickly, delays cause increase scar, non-toxic and >2mo can be treated as outpt (oral 3rd generation cephalosporin)

Treatment of UTI

• Pyelonephritis – toxic or less than 2 mo need immediate IV treatment

• Start with amp/gent until culture back• Can start with 3rd generation cephalosporin, but

missing gram pos coverage such as enterococcus• Cipro now FDA approved for complicated UTI’s in

kids• 14 day course total, can change to po when afebrile

for 48 hours

Asymptomatic Bacteriuria

• Studies have shown that ABU does not produce new scarring in the absence of reflux

• Treatment of ABU may produce more virulent strains

• Should be treated in children that have reflux• Linshaw. Kid Intern. 1996.

Renal Abscess

• In the past, usually from hematogenous route, staph• Urine cultures often negative• Now, if present more often from ascending

infections of gram- bacteria• No great studies in treatment of abscess in children,

but recommend starting with IV abx and if fail, percutaneous drainage

• Surgical treatment is last option

Xanthogranulomatous Pyelonephritis

• Destruction of perenchyma and accumulation of lipid-laden macrphages called xanthoma cells

• Case reports in children• Non specific symptoms, fever, FTT, lethargy,

palpable mass occasionally • Proteus is MC organism

XGP

• Focal and diffuse forms, focal MC in children• Can mimic malignancy on imaging, making

diagnosis difficult• Nephrectomy for diffuse, may attempt partial

for focal

Non-Surgical Management of Reflux

• Based on belief that VUR will often resolve over time and morbidity can be reduced by keeping the urine sterile

• Low dose septra, nitrofurantoin, trimethoprim alone, or in very young amoxicillin

• Some recommend UA and UCX every 6 mo, some only with symptoms

• Follow up cystogram every 18 mo• Some recommend baseline DMSA scan on higher risk

patients

Non-Surgical Management

• Resolution affected by grade of reflux, age at presentation, laterality, and presence of dysfunctional voiding

• Lower grades more likely to resolve within 5 years

• More likely to resolve if child is less than 1 year

Non-Surgical Management

• DES found in 43% of children with primary VUR

• These children are more likely to require surgery and surgery is more likely to fail

• Timed frequent voids are important, vibrating wrist watch reminder, treat constipation

Non-Surgical Managment

• Prospective studies have shown no change in renal growth or new scarring in kids with surgical vs non-surgical treatment if urine is kept sterile

• Elder. J Urol. 1997.

Non-Surgical Management

• Some advocate ending prophylaxis in children 6-8 with I-III reflux who have not had UTI’s, normal voiders, and do not have severe scarring

• ????

Non-Surgical Management

• Females with h/o recurrent childhood UTI’s need to be watched closely during pregnancy

• Need close surveillance urine cultures regardless of whether VUR was surgically corrected

• Untreated asymptomatic bacteriuria during pregnancy increases risk of low birth weight baby and preterm delivery

• Women with severe scarring or impaired renal function have increases htn, pre-eclampsia and increased fetal loss

Non-Surgical Management

• Lacking prospective proof that prophylactic antibiotics actually reduce UTI and/or renal scarring

• Studies are pending

Surgical Treatment

• Indications for surgical intervention are tailored to the individual

• Breakthrough UTI’s and poor compliance/tolerance

• UTI’s with progressive renal damage, persistent reflux, renal growth retardation, older females with persistent reflux

Surgical Treatment

• 95-98% success for grades I-IV• 80-85% for grade V• ? Need for post-operative VCUG?• Renal ultrasound in 4-6 weeks post-

operatively• Antibiotics generally continued post-

operatively but duration is individualized

Surgical Management

• 1% obstruction, if severe place PCN and wait, possible resolution, may need re-op

• New contralateral reflux – 1-18%, low grade, usually resolves

• Persistent reflux – consider failed procedure vs ureterovesical fistula

Tapered Reimplants

• Imbricate if not extremely large• Starr or Kalicinski – Kalicinski may be more

bulky• Advantage to plication is preservation of

blood supply and decreased chance of leak• Excisional tapering – needed for extremely

large ureters

Tapered Reimplant

• Taper over 10 Fr tube, 2-layer closure• Must leave stent in place to decrease

extravasation and for renal protection during period of ureteral edema

• Higher risk of urinary leakage

Surgical TreatmentEndoscopic

• Of all substances used, Deflux (cross-linked dextranomer microspheres) is only FDA approved

• Debate: specific indications for use• Some use same as indications for open

surgery, some inject after 18 mo if reflux not resolved

Deflux

• Success rates between 68-91%• Meta-analysis: 78% grade I-II, 72% grade III, 63%

grade IV, 51% grade V• Elder. J Urol. 2005.

• Success likely depends upon grade of reflux, injection technique, and surgeon experience

• Deflux can be repeated or followed by open reimplant

Endoscopic Therapy for Vesicoureteral Reflux: A Meta-Analysis

Elder, J. of Urol. 2006

• Meta-analysis of 63 articles• Included deflux, collagen, chondrocytes,

blood, and other injectables• 5,5027 patients identified• After 1 tx resolution by grade was: I/II-78.5%,

III-72%, IV-63%, V-51%

Meta-Analysis

• If first injection was unsuccessful, 68% of second injection was successful, 34% for third injection

• Lower success for duplications – 50% overall• Neuropathic bladder overall success rate was 62%• Following failed open reimplant, success of deflux

was 65%

Long-Term Follow Up of Children Treated with Deflux for VUR

Lackgren, J. of Urol. 2001.

• 221 patients identified• Followed for 2-7 years• On 3-month follow up had 68% success rate• 49 patients had repeat VCUG 2-5 years post-

op• 96% remained reflux free

Deflux

• Don’t know true durability• Those who initially were cured, may recur at a

later date• How do we follow these pt???