FP EBM Journal Club

1
FP EBM Journal Club

• Imaging Studies After First Febrile Urinary Tract
  Infection in Young Children
• NEJM 2003 348 195-202
• Ellen Chen, M.D.February 5, 2003

2
Introduction

• American Academy of Pediatrics Practice Guideline
• The Diagnosis, Treatment, and Evaluation of the
  Initial Urinary Tract Infection in Febrile
  Infants and Young Children 1999
• Recommendation 11
• Infants and young children, 2 mo to 2 yr, with
  UTI, who do not demonstrate the expected clinical
  response within 2 days of antimicriobial therapy,
  should undergo ultrasonography promptly. Voiding
  cystourethrography (VCUG) or radionuclide
  cystography (RNC) is strongly encouraged to be
  performed at the earliest convenient time.
  Infants and young children who have the expected
  response to antimicrobials should have a
  sonogram, performed at the earliest convenient
  time a VCUG or RNC is strongly encouraged.

3
(Strength of evidence fair)

• The article under discussion examines these
  recommendations, offering no definitive answers
  but raising interesting questions.

4
Epidemiology of UTIs by sex

• UTIs occur in 1.5 to 5 times as many males as
  females in the neonatal period
• Prevalence in febrile girls lt 1yr is 6.5 vs 3.3
  in boys
• Prevalence in febrile girls between 1 to 2 yr is
  8.1 vs 1.9 in boys

5
After pediatric febrile UTIs why all the
concern?

• Recurrent UTIs increase the risk of renal damage
  in children.
• There may be a delay in diagnosis and treatment
  of UTIs in infants and young children.
• Difficulty of diagnosis
• Social factors

6
After pediatric febrile UTIs why all the
concern?

• UTIs may indicate there is an obstructive lesion
  or vesicoureteral reflux (VUR) which can cause
  chronic pyelonephritis/ renal damage.

7
Urinary Obstruction

• Picked up as hydronephrosis/ dilated ureters on
  US
• Obstructive lesions include ureteropelvic
  junction obstr, utererovesical junction obstr,
  multicystic kidney dz, ureterocele/ ectopic
  ureter, duplicated collecting system, posterior
  urethral valve obstr, urethral atresia, pelvic
  tumors.

8
Vesicoureteral Reflux

• Picked up by VCUG or RNC
• Prosposed pathophysiology an inadequate valvular
  mechanism at the UVJ due to deficiency of
  intravesical ureter muscle or length.
• Functional obstruction (dysfunctional voiding,
  neurogenic bladder, bladder instability) may
  contribute to VUR

9
(No Transcript)
10
(No Transcript)
11
VUR resolution

• Grade I and II 80 resolve
• Grade III and IV resolution ranges from 25-50
  in one study. Another study estimates 15 in 5
  yrs, 52 in 10.

12
VUR associated with Scarring

• Pts with high grade VUR are 4-6 times more likely
  to have scarring than low grade VUR and 8-10
  times more likely than those without VUR.
• VUR and infection is thought to cause renal
  scarring, also called reflux nephropathy.

13
VUR Management

• Medical Antibiotic prophylaxis QD until reflux
  resolves or child reaches age 5-7 yrs. Periodic
  Ucx (Q3mo) and VCUG (Qyr)
• Surgical Reimplantation of ureters or injections
  behind the ureters.

14
Intermediate Clinical Outcome

• Renal scarring as imaged by 99m-technetium
  demercaptosuccinic acid (DMSA) scans is been used
  to measure renal damage from UTIs/ VUR.

15
Bottom Line Clinical Outcome

• Preventing decreased renal function and/or
  secondary hypertension

16
The Study

• Imaging Studies after a First Febrile Urinary
  Tract Infection in Young Children
• Alejandro Hoberman, M.D., Martin Charron, M.D.,
  Robert W.Hickey, M.D., Marc Baskin, M.D., Diana
  H. Kearney, R.N., and Ellen R. Wald, M.D.

17
The Study Question

• Did imaging studies alter management or improve
  outcomes in young children with a first febrile
  urinary tract infection?

18
Study design

• A natural history and prospective cohort of 309
  children (1 to 24 months old) who received US and
  DMSA scan within 48 hours of diagnosis of first
  febrile UTI, VCUG after 1 month, and repeat DMSA
  scan 6 months later.

19
Study design

• Based on data from earlier study Oral vs Initial
  IV Therapy for UTIs in Young Febrile Children in
  Pediatrics 199910479-86. This multicenter,
  randomized clinical trial compared oral cefixime
  (14 days) to IV cefotaxime (3 days) followed by
  oral cefixime (11 days) and found no difference
  between the two groups.

20
Study design

• 1992- 1997
• Children eligible if rectal temp min 38.3 C and
  if pyuria or bacteriuria present
• Exclusion if 1) neg Ucx, 2) hypersentivity to
  cephalosporins, 3) Gram cocci on GS, 4) h/o UTI
  or abnormalities of urinary tract, 5) received
  abx within 48hrs or 7) underlying chronic dz.

21
Imaging Design

• US and DMSA within 48hrs
• VCUG in one month
• Grade II and above received prophylactic TMP or
  nitrofurantoin QD for 11 mo or until reflux
  classified grade I or less
• DMSA repeated six months later
• Scans interpreted by 2 independent radiologists
  who were unaware of the patients test results or
  characteristics

22
Follow-up design

• UCxs obtained at 3 mo and 6 mo for surveillance
  and at the time of febrile illness
• Monthly interviews via telephone calls and
  visits followed for history of fever or other
  s/sx c/w UTI

23
Results
Age 4-7 wk 4.2 8w-11 mo 67.3 12-24 mo 27.5
White 72.5 Black 19.4 Other 7.1
Female 89.3 Male 10.7
24
Results

• 12 of the children had abnormal US
• Using VCUG as the gold standard, dilated tract on
  US as predictor of VUR only had a sensitivity of
  0.10 and a PPV of 0.40.

25
Results

• VUR Grade III or IV was more likely to occur
  among children with abnormal US findings than
  those with normal findings (10 of 30 vs. 40 of
  272, P0.02)

26
Results

• Initial DMSA scan
• 61 of children with signs of acute
  pyelonephritis.
• One child with previous scarring
• Repeat DMSA scan was performed in 89 of the
  children
• 9.5 had renal parenchymal involvement
• Renal scarring was more likely to occur in
  children with documented VUR (15 vs. 6, P0.03)
  
• No relation was found between renal scarring and
  age at dx, duration of fever before or after
  therapy.
• Only degree of VUR was significantly associated
  with higher incidence of renal scarring on
  logistic-regression models

27
Validity of this Prognostic Study

• Study population is a representative primary care
  cohort. (Greater generalizability per authors)
• Patients were entered into the study at a common
  early point of illness after the first febrile
  UTI.
• Follow-up occurred for six months with an
  acceptable dropout rate.

28
Validity of this Prognostic Study

• Objective outcome criteria were applied in a
  blind fashion.
• Adjustment for prognostic factors The authors
  state that independent predictor variables and
  their interaction were evaluated in
  logistic-regression models to determine their
  influence on scarring.

29
Summary

• This study confirms previous studies that US is
  not a sensitive test for the detection of VUR.
• Further studies may focus on the question of US
  as predictor of high grade VUR.
• In this study, US did NOT change management or
  clinical outcome. The authors state 95
  confidence that the true proportion of children
  with clinically important findings that would
  modify management is lt1.

30
Summary

• In this study, 39 of the study population was
  diagnosed with VUR. This is c/w estimates that
  30-40 of febrile infants and young children have
  VUR.
• This study also confirms that VUR is associated
  with renal scarring.
• Incidence of renal scarring (9.5) was lower that
  the 30 previously reported.

31
Question 1

• Is VCUG the only study needed in children less
  than 24 months of age with a first febrile UTI?

32
Question 2

• How does fetal ultrasound affect our decision to
  include US in the evaluation of infants/ young
  children with first febrile UTIs?

33
Fetal renal ultrasound

• Factors to consider in prenatal diagnosis of
  hydronephrosis as screening test
• Measurement criteria for AP pelvic diameter
• Gestational age
• Maternal hydration
• Consideration of other anomalies
• Fetal urine flow is higher than neonatal flow.

34
Question 3

• Does antibiotic prophylaxis change clinical
  outcome? (Will VCUG be necessary if the answer
  is no?)
• VUR management studies have compared medical vs
  surgical therapy but have not included a placebo
  or observation control group.

35
Question 4

• Bottom Line Clinical Outcome What are the
  long-term implications of small renal scars
  identified by DMSA scans?
• Previous studies showing an association betw
  renal scars and development of HTN, preE, RI and
  ESRD were based on intravenous pyelography, a
  test much less sensitive than DMSA.

36
Bibliography

• American Academy of Pediatrics. The Diagnosis,
  Treatment, and Evaluation of the Initial Urinary
  Tract Infection in Febrile Infants and Young
  Children. Pediatrics 1999103843-52.
• Hoberman, A. M.D., et al. Imaging Studies after
  a First Febrile Urinary Tract Infection in Young
  Children. NEJM 2003348195-202.
• Hoberman, A. M.D., et al. Oral vs Initial IV
  Therapy for UTIs in Young Febrile Children.
  Pediatrics 199910479-86.
• ODonovan, Donough, M.D. Urinary tract
  infections in newborns. UpToDate 2002.
• Ozcan, T and Bahado-Singh. Prenantal diagnosis
  of fetal pyelectasis, VUR, and hydronephrosis.
  UpToDate 2002.
• Rose, B and Herrin, J. Diagnosis and treatment
  of VUR and chronic pyelonephritis. UpToDate
  2002.
• Ross, J and Kay, R. Pediatric Urinary Tract
  Infection and Reflux. American Family Physician,
  March 15, 1999.
• Stapleton, F.B. Imaging Studies for Childhood
  Urinary Infections. Editorial. NEJM
  2003348251-52.

37
(No Transcript)