Urinary Tract Infections in Children Diagnostic Imaging based on Clinical Practice Guidelines Emily D. Kucera, M.D. Assistant Professor, UMKC

Learning Objectives State prevalence, associations, and consequences of febrile UTI’s in children Discuss imaging options and timing of procedures Discuss classification systems used in radiologic reports Review variations of Clinical Practice Guidelines from reputable institutions- will discuss CMH guidelines and include others in handout.

Febrile UTI’s Most common serious bacterial infection occurring in infancy and childhood Affects at least 3.6% of boys, 11% of girls 10-30% of children with febrile UTI’s will develop renal scarring

Diagnosis of UTI Combination of clinical features and presence of bacteria in urine > 10⁵ cfu/ml Acute pyelonephritis = UTI + fever > 38℃ (100.4℉) - most common in infants Cystitis = symptoms of dysuria, frequency, suprapubic pain in toilet-trained child

Urinary Tract Infections in Children Prevalence of positive culture in children 0-21 years 8.8 - 14.8% Males < 1 year (3%); males > 1 year (2%) Females < 1 year (7%); females > 1 year (8%) 50-91% of children with febrile UTI’s are found to have acute pyelonephritis All infants < 8 weeks of age with fever should be suspected of having an upper tract infection/pyelonephritis

Organisms Associated with UTI’s in Children Escherichia coli - Most common organism; causative agent in > 80% of 1st UTI Klebsiella species - 2nd most common organism. Seen more in young infants Proteus species - May be more common in males Enterobacter species - cause < 2% of UTI’s Pseudomonas species - cause < 2% or UTI’s Enterococci species- Uncommon > 30 days of age Coagulase-negative staphylococcus - Uncommon in childhood Staphylococcus aureus - Uncommon > 30 days of age Group B streptococci - Uncommon in childhood _ +

Risk Factors for UTI’s Male Female Uncircumcised < 1 yr (5-20 x higher risk than circumcised males) All < 6 months Female < 1 yr non-African American race fever > 39℃ (102.2℉)

Atypical UTI’s Seriously ill Poor urine flow Abdominal or bladder mass Raised creatinine Septicemia Failure to respond to treatment within 48 hrs Infection with non- E. coli organisms

“Seriously Ill”

Recurrent UTI’s 2 or more episodes of acute pyelonephritis / upper urinary tract infection or 1 episode of acute pyelonephritis + > 1 episode of cystitis > 3 episodes of cystitis/lower urinary tract infection

Recurrent UTI’s Girls are more prone to recurrences with age Children who present early in life with UTI are more prone to recurrences ¾ of children presenting < 1 year will have recurrences > 1 year of age ~ 40% of girls, 30% of boys Overall incidence of UTI recurrences after pyelonephritis is 20.1%

Asymptomatic Bacteriuria Most common in boys in early infancy 1.6% boys < 2 months affects 0.2% in school age boys Girls have lower rates until 8-14 months 1.5 - 2% in school age girls; peak prevalence 7-11 years of age

Dysfunctional Elimination Syndromes (DES) Constipation- seen in 50 % of DES and VUR May induce uninhibited bladder contractions Rectal distention causes bladder distortion causing detrusor dyssynergism and ureteral valve incompetence Bladder instability Infrequent voiding (< 4 times/day) Contributes to UTI’s and slower resolution of reflux

Associations with UTI’s Dysfunctional Elimination Syndromes (DES) 67% of girls with DES develop UTI’s 40% of girls with UTI’s have DES 20% of girls with DES have reflux

A 6 month old female has had 3 UTI’s A 6 month old female has had 3 UTI’s. Which of the following is the best approach? No imaging needed US + VCUG MRI DMSA scan

Imaging Procedures Ultrasound - detect renal anomalies, dilatation, renal sizes, bladder abnormalities, ureteral dilatation VCUG - Voiding Cystourethrogram- assess for vesicoureteral reflux, bladder volumes, bladder abnormalities, urethral anatomy DMSA Scintigraphy- assess for pyelonephritis and renal scarring Radionuclide Cystogram - assess for VUR; used infrequently at CMH

Abnormal Ultrasound Findings Dilatation of at least 1 calyx Anteroposterior (AP) diameter of the renal pelvis > 7 mm; ureteral diameter > 5 mm Focal scarring Difference of > 10% of length between kidneys or renal length > 2 standard deviations above mean Bladder abnormality

Hydronephrotic MCDK Normal

Society of Fetal Urology Classification of Prenatal and Postnatal Hydronephrosis

1 2 4 3

Duplicated Collecting Systems Duplication of renal pelvis and ureter is one of the most common anomalies of the urinary tract Partial - range from bifid renal pelvis to 2 ureters joining anywhere proximal to uterovesical junction Complete - 2 separate ureters with the upper pole ureter draining more caudal and medial than the lower pole ureter = ectopia (Weigert-Meyer rule) Ureteral duplication is of no clinical significance unless it is complicated with ectopia, VUR, UTI, or obstruction

Duplicated Collecting Systems Non-dilated Dilated

Voiding Cystourethrogram Requires bladder catheterization: 8 Fr feeding tube (No balloon) Lidocaine gel used on majority of patients Local analgesia Dilates meatal opening Radiation: Decreased dose with pulse and digital techniques 1-3% risk of UTI

Need for Sedation Sedation not needed in the vast majority of the cases CMH Guidelines for sedation follow the AAP and ASA (Anesthesia) Guidelines If need for anxiolysis, please directly communicate with the Radiologist who will be performing the exam at the time of scheduling Child Life personnel available at the Main and the South Campuses.

Vesicoureteral Reflux International Reflux Grading System of VUR

Bilateral Grade 2 Grade 1 Grade 3

Vesicoureteral Reflux Incidence 20-40 % of children presenting with UTI Girls 17-34% Boys 18-45% Increased incidence if family history of VUR Parent to Child: up to 66% Siblings: up to 34% Overall prevalence in general population 1-3%

Prevalence of VUR by Age Prevalence in 54 studies of UTI in Children

Prevalence of VUR Girls: 0 - 18 yrs Grade I - 7% Grade II - 22% Grade III - 6 % Grade IV - 1% Grade V - < 1%

DMSA Scintigraphy Intravenous injection of a radiopharmaceutical labelled with TC-99m DMSA is concentrated in the proximal renal tubules. Identifies functioning renal tissue Images obtained between 2-6 hours after injection Usually requires sedation in children < 3 years of age

Timing of DMSA Acute imaging: Within 5-7 days of acute infection 90% sensitivity for pyelonephritis Cannot differentiate pyelonephritis from renal scarring Delayed imaging ~ 6-12 months after UTI Assess for renal damage Gold standard for detection of parenchymal defects

DMSA Renal Scarring Normal

Risk of Renal Parenchymal Defects In the presence of VUR, more frequent in boys and children > 1 year of age ~ 5% of children presenting with 1st febrile UTI will have parenchymal defects Pyelonephritis and renal scarring occur as frequently in children without VUR as with VUR In the general population: 0.5 - 0.13% girls versus 0.17 - 0.11% boys will develop reflux nephropathy

Renal Parenchymal Defects Boys more susceptible to developing dysplasia or parenchymal defects in utero Girls tend to acquire their parenchymal defects at a later age Infants have a higher risk of renal damage Recurrent UTI’s a significant risk factor for girls, not boys The only effective way to reduce renal scarring associated with UTI’s is early diagnosis and prompt, effective treatment

Renal Damage Of children with acute pyelonephritis diagnosed by DMSA, 38-57% will develop permanent renal scarring Seen in 78% of infants with dilating reflux(grades III-V), obstruction, clinically relevant anomalies (renal aplasia, ectopic kidney, complete duplication) Seen in 15% of infants without the above diagnoses

Risk of Renal Scarring versus # of UTI’s

A 5 year old female has recurrent febrile UTI’s A 5 year old female has recurrent febrile UTI’s. What imaging study would be useful to detect renal scarring? VCUG US CT abdomen DMSA scan

Recommendations and Guidelines No universally accepted work-up for children with UTI’s Lack of consensus among different guidelines Complex approaches; Regional variations Multiple tables dividing children into different age groups Classifying UTI’s into different variants Determine nature and timing of imaging studies

Utility of Diagnostic Imaging Procedures Identifying pathologic malformations and risk factors Changing management approaches Affecting follow-up monitoring

Outside of Guidelines Infants and children: known pre-existent uropathy or underlying renal disease hydronephrosis or obstruction neurogenic bladder with urinary catheters in situ immunosuppressed

Clinical Practice Guidelines Children’s Mercy Hospitals (last edited 2007) Included in Handout American Academy of Pediatrics (last edited 1999) Cincinnati Children’s (last edited 2006) NICE (National Institute for Health & Clinical Excellence) (2007) Royal College of Physicians (1991)

CMH Guidelines Ultrasound ⇓ Boys- All VCUG Girls < 36 months If identification of pyelonephritis or renal scarring DMSA Boys- All Girls < 36 months Girls 3-7 years of age with fever > 38.5℃ ( 101.3 ℉)

CMH Guidelines Observation without imaging ⇓ If subsequent UTI Ultrasound VCUG If pyelonephritis or renal scarring DMSA Girls > 3 years with fever < 38.5℃ (101.3℉) All Girls > 7 years

Children’s Mercy Guidelines Children who should have RUS + VCUG after 1st febrile UTI Failure of good response after 48-72 hrs of effective antibiotics Infection with an unusual organism Lack of assurance of close follow up Abnormal urine stream, abdominal mass Recurrence of febrile UTI

Timing of VCUG during Acute Illness VCUG during first 10 days of treatment IF The patient has good response to Tx; afebrile > 24 hours The infecting bacteria is susceptible to antibiotic administered Voiding pattern has normalized to pre-infection Younger infant should have no dysuria and normal behavior

After 24 hours without a fever No need to do VCUG An uncircumcized 2 month old male was admitted with a febrile UTI that has not responded to antibiotic therapy after 48 hours. When is the best time to perform a VCUG? On the day of admission After 24 hours After 24 hours without a fever No need to do VCUG

Vesicoureteral Reflux Classification per CMH Clinical Practice Guidelines Mild: grade I and II, unilateral grade III in a child < 2 years old Moderate-Severe: all other grade III’s, IV, V

Referral to Pediatric Urologist or Nephrologist Any child with evidence of urinary tract obstruction: Refer to Pediatric Urologist VUR > Grade III or evidence of renal damage VUR > Grade III with break through infection Any child with Grade V VUR should be referred immediately. The presence of Grade IV and lower grades of VUR + the presence of renal damage frequently reflects intrauterine VUR and damage rather than acquired damage.

Recommendations for Follow-up VCUG’s CMH Clinical Practice Guidelines: In children maintained on prophylactic Antibiotics: every 2 years with grades I and II, and for those < 2 years with unilateral grade III every 3 years for all others with grade III and IV

Conclusions Better understanding of the impact of febrile UTI’s on children Better understanding of some of the radiologic procedures and findings Understanding of CMH Clinical Practice Guidelines and ability to compare with other Clinical Practice Guidelines from reputable institutions Effects on diagnostic imaging and timing of imaging procedures

AAP Guidelines Every febrile infant or young child, 2 months-2 years of age, should be imaged with ultrasound and a study to detect for VUR Those who do not demonstrate the expected clinical response within 2 days of antibiotics, should have ultrasound promptly and reflux study at earliest convenience

Cincinnati Children’s Guidelines Children with 1st UTI, need Ultrasound and Voiding Cystogram: all boys girls age < 36 months (dependent on ability to verbalize dysuria girls 3-7 years with fever > 38.5 ℃ (101.3℉)

Observation without Imaging per Cincinnati Children’s Girls > 3 years with fever (< 38.5℃) All girls > 7 years Follow up with dipstick of routine urinalysis if symptoms of UTI

NICE Guidelines Not recommend antibiotic prophylaxis following 1st UTI, even in child with VUR Not routinely evaluate for VUR with imaging Infants < 6 months with 1st UTI that responds to treatment - US within 4-6 weeks of UTI Infants > 6 months- US not recommended unless atypical UTI

NICE Guidelines Infants < 6 months Responds to Tx within 48 hours Atypical UTI Recurrent UTI Ultrasound during acute infection No Yes* Yes Ultrasound within 6 weeks Yesª DMSA within 4-6 months following infection VCUG *In a child with non-E. coli UTI, responding well to antibiotics and no other features of atypical infection, ultrasound can be requested on a non-urgent basis ª If Ultrasound abnormal, consider VCUG

NICE Guidelines Children 6 months - < 3 yrs Responds well to Tx within 48 hours Atypical UTI Recurrent UTI Ultrasound during infection No Yes* Ultrasound within 6 weeks Yes DMSA 4-6 months following acute infection VCUG Noª *In a child with non-E. coli UTI, responding well to antibiotics and no other features of atypical infection, ultrasound can be requested on a non-urgent basis ªConsider VCUG if dilatation on ultrasound, poor urine flow, non-E. coli infection, family history of VUR

NICE Guidelines Children > 3 yrs Responds well to Tx within 48 hours Atypical UTI Recurrent UTI Ultrasound during acute infection No Yes* Ultrasound within 6 weeks Yes DMSA 4-6 months following acute infection VCUG *In a child with non-E. coli UTI, responding well to antibiotics and no other features of atypical infection, ultrasound can be requested on a non-urgent basis

Royal College of Physicians in 1991 Infants: Ultrasound, VCUG, and DMSA Children 1-7 yrs: Ultrasound and DMSA > 7 yrs: Ultrasound and potential additional exams dependent on ultrasound findings

Guidelines of the Royal College of Physicians Ultrasound should be considered in all cases of children with 1st UTI. Late DMSA scintigraphy in children up to 7 years VCUG in children < 1 year