uti in children. introduction pediatric utis often signal an underlying genitourinary tract...
TRANSCRIPT
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Uti in children
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Introduction
Pediatric UTIs often signal an underlying genitourinary tract abnormality
Can lead to renal scarring with resultant hypertension and renal failure
Difficult to diagnose because symptoms are non-specific in this age group and testing is often invasive
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Pediatric UTIs: Epidemiology
Prevalence Girls—6.5-8% Boys—2-3%
Uncircumcised boys have a 5-20 X increase in UTIs vs circumcised boys
Occurs in about 7% of children <2 who present with fever without a source
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Epidemiology (continued)
Incidence of vesicoureteral reflux (VUR) is 1% in children < 2 yoa. 50% of kids <1 yoa with UTI have VUR
Early renal scarring is nearly twice as common in this age group.
Incidence of scarring increases with each subsequent UTI Scarring occurs in 5-38% of febrile UTI’s.
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Figure 1Prevalence of VUR by age. Plotted are the prevalencesreported in 54 studies of urinary tract infections inchildren (references in Technical Report).
Pediatrics 1999; 103: 843-852
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Figure 2Relationship between renal scarring and number ofurinary tract infections.16
Pediatrics 1999; 103: 843-852
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UTI: Classiffication
Classification: Upper tract infection
Acute pyelonephritis- fever, bacteriuria, systemic symptoms
Lower tract infection Urethritis Cystitis Voiding symptoms, little or no fever, no
systemic symptoms
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Clinical Presentation
Age and gender dependent 0 - 2 months:
Fever 2 mo.– 2 y/o:
Fever (>38 C) Irritability Vomiting and Diarrhea Decrease appetite Between 1-2 y/o = crying on urination, foul
smelling odor
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Clinical Presentation
2 y/o – 6 y/o: Systemic symptoms Fever Flank or back pain Urgency, urinary incontinence, dysuria Suprapubic or abdominal pain Foul smelling odor
> 6 y/o and adolescents: Same as above
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Urethritis
In female infants Part of a diaper
dermatitis In adolescent girls
and boys Presenting sign of
STD
In pre-school and school age girls Part of “non-specific”
vulvovaginitis Generally environmental Bubble bath Nylon panties (also biker
shorts, leotards, bathing suits)
Poor hygiene (not wiping, wiping back to front)
Overzealous hygiene Use of baby powder,
perfumes
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Symptoms of urethritis
Dysuria Reluctance to void Perineal discomfort, erythema May be associated with vaginal
irritation and erythema in girls In older boys, urethral discharge In adolescent girls associated with
PID symptoms
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Cystitis
Afebrile usually Frequency Enuresis Dysuria Reluctance to void
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Pyelonephritis
Usually associated with fever and systemic signs 2° renal parenchymal inflammation
Older children Flank pain or abdominal pain
Younger children Fever, irritability, vomiting, poor
feeding
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Pyelonephritis - Significance
EACH infection results in scar formation and reduced renal function
After diabetes mellitus and collagen vascular disease, undetected renal disease and untreated childhood UTI may be responsible for: A large of portion of ESRD in adults A huge need for dialysis and transplantation
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Pyelonephritis - Significance
Untreated childhood UTI responsible for: Hypertension Impaired kidney function Complications of pregnancy
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Causes and course of UTIGut flora Bacterial virulence
Uropathogenic strain Colonisation of the urethra and the perineum (in females the vagina)
Mucosa barriere
Host Increased adherence immunstatus
VUR obstruction foreign body previous inflammations
cystitis
akute pyelonephritis
healed urosepsis scar
hypertension CRF...
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Risk Factors
Age <1 year Female gender Uncircumcised
males Constipation Voiding
dysfunction
Improper wiping Genitourinary
abnormalities Vesicoureteral
reflux Obstruction
Colonization with virulent E. Coli
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Signs and Symptoms – Children 2 months to 2 years
Fever—usually unexplained Vomiting and/or diarrhea Abdominal Pain Failure to thrive Malodorous urine Crying on urination
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Signs and Symptoms – Children >2
Fever Vomiting and/or diarrhea Abdominal pain Malodorous urine Frequency and/or urgency Dysuria New incontinence
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Summary
Urinary tract infections are a common cause of fever without a source in children <2 and can lead to renal scarring, HTN or ESRD. Rapid treatment is essential.
Symptoms are non-specific and thus a high level of suspicion is required
Urine culture is required for diagnosis, and should be obtained by catheterization or SPA when child is ill or infection is suspected
Treatment requires a 7-14d course of antibiotics Prophylactic abx are required after initial
treatment All Children <2 require 2 imaging studies after
initial UTI
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References
Committee on Quality Improvement, Subcommittee on Urinary Tract Infection. The diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics 1999; 103:843-852
Layton, KL. Diagnosis and Management of Pediatric Urinary Tract Infections. Clinics in Family Practice 2003; 5: 2
Chon DH, Frank CL, Shortliffe LM. Pediatric Urinary Tract Infections. Pediatric Clinics of North America 2001; 48: 1441-1459
Linderd KA, Shortliffe LM. Evaluation and management of pediatric urinary tract infections. Urologic Clinics of North America 1999; 26: 719-728
McCollough M, Sharieff G. Marx: Rosen’s Emergency Medicine: Concepts and Clinical Practice, 5th ed.2002; 2327-2334
Acute Urinary Tract Infections Clinical Effective Committee. Evidence based clinical practice guideline for patients 6 years of age or less with a first time acute urinary tract infection. Cincinnati (OH): Children’s Hospital Medical Center 1999; 1-14
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Patient groups Infants of 1 year Girls and boys Recurrent UTI (no abnormalities) Mild VUR (grade I and II)
Options Long-term low dose antibiotics (Cochrane review)
(Trimethoprim, Nitrofurantoin, Cotrimoxazole) Intermittent treatment of UTIs
Time horizon 3 years of long-term antibiotics and follow-up to end
stage renal disease
NHS perspective
long-term antibiotic treatment for preventing recurrent urinary tract infections (UTI) in children
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Model Structure for UTI
No UTI
1 UTI
2 UTIs
3 UTIs
4 UTIs
Age atESRD onset
Frequency of recurrent UTIs
Number of pyelonephritic attacks
Progressive renal scaring
End-stage renal disease
TransplantPyelonephritic
attack
Pyelonephritic attack
Pyelonephritic attack
Pyelonephritic attack
Number of attacks
Progressive renal
scaringDevelopment
of ESRD
Dialysis
No UTI
1 UTI
2 UTIs
3 UTIs
4 UTIs
Age atESRD onset
Frequency of recurrent UTIs
Number of pyelonephritic attacks
Progressive renal scaring
End-stage renal disease
TransplantPyelonephritic
attack
Pyelonephritic attack
Pyelonephritic attack
Pyelonephritic attack
Number of attacks
Progressive renal
scaringDevelopment
of ESRD
Dialysis
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The evidence
Effectiveness• Existing reviews (variable quality)• Meta analysis, Multiple parameter synthesis• Probabilistic trial based model
Natural history• Epidemiological studies• Pooled trial baselines• Registry studies• Clinical judgement
Quality of life • Published studies• Survey
Costs • Published studies• Published unit costs and dosage (BNF, PSSRU, CIPFA)
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Antenatal Period
The most common cause is physiologic dilation.
Metanephric urine production begins at 8 weeks, even before ureteral canalization is complete.
Transient obstruction with hydronephrosis occurs.
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Embryology
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Pathophysiology:
Anatomic and functional processes interrupts the flow of urine.
There is a rise in ureteral pressure causing stretching and dilation; if pressures continue to rise, leads to decline in renal blood flow and GFR.
When significant obstruction is persistent, it affects nephrogenic tissue and results in varying degrees of cystic dysplasia and renal impairment.
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Grading of Severity of Hydronephrosis
Grade Central RenalComplex
RenalParenchymalThickness
0 Intact Normal
1 Slight splitting Normal
2 Evident splitting Normal
3 Wide splitting Normal
4 Further dilatation Thin
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Most Common Causes in Neonates:
Ureteropelvic Junction Obstruction Ureterovesical Junction Obstruction Posterior Urethral Valves Eagle-Barrett Syndrome (a.k.a.
Prune Belly Syndrome) Vesicoureteral Reflux Ureterocele
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Treatment for UPJ: Pyeloplasty
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Diagnosis
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Urine Collection
Clean Catch acceptable for toilet trained children (wearing underwear or pull-ups) Ensure cleansing with antiseptic
towelette Catheterized specimen in diapered
children Suprapubic bladder tap in <6 month
old child is guaranteed sterile
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Leukocyte Esterase
Has to accumulate in urine Insufficient accumulation possible in
small infants who void frequently Infants <3 months old may not have
mature enough immune system to induce leukocytes in urine (beware neutropenia on CBC)
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Nitrites
By-products of E. coli and other lactose fermenters (glucose digestion)
Insufficient accumulation possible in small infants who void frequently
Insufficient accumulation possible in older child during the day and in older patient who has significant frequency
If positive, highly suggestive of UTI (high specificity)
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Microscopy
>10 WBC/hpf on spun urine Bacteria on unspun urine are
common unless catheterized specimen
Gram stain is very helpful on spun urine
Standard UA plus gram stain is “enhanced UA”
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Urine Culture
>100,000 cfu per mL on any culture >10,000 cfu per mL on cath
specimen ANY bacterial growth on bladder tap
(at least 1,000 cfu/mL)
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Sensitivity and Specificity of Components of the UA
TestSensitivity %
(Range)Specificity %
(Range)
Leukocyte esterase
Nitrite
Leukocyte esterase or nitrite positive
Microscopy: white blood cells
Microscopy: bacteria
Leukocyte esterase or nitrite orMicroscopy positive
83 (67.94)
53 (15-82)
93 (90-100)
73 (32-100)
81 (16-99)
99.8 (99.100)
78 (64-92)
98 (90-100)
72 (58-91)
81 (45-98)
83 (11-100)
70 (60-92)
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Urine Cultures
Held for 48 h but usually positive at 24 h for true UTI
Requires another day for ID of organism
May require another day for sensitivities
If contains skin flora (S. epi., S. aureus or α-strep.) considered contamination secondary to poor specimen collection
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Diagnosis
Urinalysis Can be obtained by most convenient
means if infant is not ill UTI CANNOT be diagnosed with UA
alone If suspicious UA, the Urine Culture must
be obtained via SPA or catheter specimen
If UA does not suggest UTI, it is reasonable to follow child clinically
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Table 1. Sensitivity and Specificity of Components of the Urinalysis, Alone and in Combination (References in Text)
Test Sensitivity %(Range)
Specificity %(Range)
Leukocyte esterase 83 (67-94) 78 (64-92)
Nitrite 53 (15-82) 98 (90-100)
Leukocyte esterase or nitrite positive
93 (90-100) 72 (58-91)
Microscopy: WBCs 73 (32-100) 81 (45-98)
Microscopy: bacteria 81 (16-99) 83 (11-100)
Leukocyte esterase or nitrite or microscopy positive
99.8 (99-100) 70 (60-92)
Pediatrics 1999; 103: 843-852
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Diagnosis
Urine Culture MUST be collected via catheter or SPA UTI CANNOT be diagnosed from a bag
specimen Diagnosis of UTI requires Urine Culture
LOE--Strong
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Urine Collection: Suprapubic Aspirate
“Gold standard” - >99% specificity Positive culture: any number of g-
bacilli or >3000 CFU of g+ cocci
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Urine Collection: Transuretheral Catherization
>105 CFU - 95% specificity 104 – 105 CFU – infection is likely 103 – 104 CFU – Suspicious <103 CFU – infection unlikely
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treatment
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Treatment
May initiate treatment either orally or parenterally
Admit and use parenteral antibiotics if toxic, dehydrated or unable to take PO
Choices: TMP/SMX Cephalosporin Amoxicillin (check local resistance)
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Treatment--continued
Improvement should be seen in 24-48 hours
If not having expected clinical response in 2 days, re-culture, consider changing antibiotics and do imaging studies
Complete 7-14 day course of antibiotics 14 days should be given for those that were
ill with clinical evidence of pyelonephritis
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Prophylaxis
After completion of initial antibiotics, children should be give a prophylactic dose of antibiotics until imaging studies complete
Antibiotic should have high urinary excretion and low serum and fecal levels, thus minimizing the development of resistance.
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Imaging
Needs to be performed in ALL children <2 years old with initial UTI
Need to perform at least 2 studies to image the upper and lower urinary tracts
Acute imaging only necessary when appropriate clinical response is not achieved within 2 days
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Ultrasound
Should be done on all infants < 2yoa after their initial UTI
Helps to detect hydronephrosis and ureteral dilation
Has replaced IVP Need additional study to evalute VUR Is not as sensitive as renal cortical
scintigraphy (DMSA) for detecting inflamation and scarring
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Voiding Cystourethrography (VCUG)
Used to identify and grade reflux Also evaluates the urethra and bladder for
abnormalities – important for boys who may have posterior urethral valves and girls with voiding dysfunction
Radionuclide cystography (RNC) – can also evaluate reflux, but does not delineate the lower tract anatomy well. Can be used for follow-up exams as has low ratiation dose
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Renal Cortical Scintigraphy (DMSA)
Very sensitive for evaluating acute inflammation from pyelonephritis as well as renal scarring
Role in clinical management is still unclear
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Treatment
No “short course” therapy for small children
No “short course” therapy for males Empiric therapy is directed at
organisms and adjusted for age. Choose narrowest spectrum
allowable considering host factors Adjust therapy when sensitivities
available
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IV antibiotics-Indications
Any person of any age who appears clinically toxic or who has neutropenia
Infants <1 mo until bacteremia, sepsis, & meningitis ruled out
Children unable to tolerate oral antibiotics
Immunocompromised patients
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Antibiotic choice
Neonates Ampicillin plus a second antibiotic (usually
gentamycin or cefotaxime) to cover for GBS, Listeria, as well as gram negative organisms
S. aureus and S. epi. can cause hematogenous pyelonephritis (in children instrumented :ET tube,central lines, etc)
Vancomycin may be indicated for toxic patients or those unresponsive to initial therapy
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Therapy
Cefixime (Suprax) oral is as effective as parenteral ceftriaxone
Cefpodoxime (Vantin) Bad tasting 10 mg/kg/day
Fluoroquinolones are expensive and ”off label” in pedi
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Bacterial virulence Bacterial spectrum at the Ist Dept. of Pediatrics, in 2002-2003
N=7850 (%) E. coli 49 Enterococcus faecalis 13 Proteus indol neg. 10 Klebsiella 7 Pseudomonas spp 7 Enterobacter spp 6 Proteus indol pos 3 Staphylococcus 3 Other 2
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Sensitive host
Age related factorsAnatomy (short urethra, phymosis and
adhesio cellularis preputii et labia minora, diaper)
colonization Immunological susceptibility
Mucosal barrier Inherited/acquired
immunresponse Inherited/acquired
Ex: IgA deficiency, P1 blood group
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Sensitive host
Anatomical malformationsobstructionVURmeningomyelokeleprune-belly syndromeStone disease, etc
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Age-related incidence of UTI
0 10 20 30 40 50 60 70 80
age (years)
rela
tive
risk
boys girls
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neonate child > 3(6)y systemic infection cystitis hospitalize outpatient i.v. antibiotics (AB) per os AB
US
Adjust treatment according to bacteriology
(in case of relaps)
MCU US 4-6 weeks after the acute phase norm: care for 1 y pathological: scintigraphy (ivu) prophylaxis+surg.
Management of UTI
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Prognosis
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UTI Controversy #1:Antibiotic Prophylaxis
Indications grade 1 VUR frequent UTI recurrences
Problems Pt Rxd with antibiotic prophylaxis
Increased infection with Proteus and Enterobacter pseudomonas and Candida increased in children
with urogenital abnormalities Drug toxicity and sensitivities
Antimicrobial choices (qhs better) TMP-SMX or Nitrofurantoin (GI disturbance) Keflex if < 3 months Quinolones in some circumstances
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Posterior Urethral Valves
Abnormal congenital mucosal folds that are thin membranes impeding bladder drainage.
Most common obstructive urethral lesion in male newborns found at the distal prostatic urethra.
Incidence is approx’ly 1 in 8,000 males. Approx’ly 50% have reflux. VCUG is the modality of choice.
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Radiographic signs of PUV:
distended prostatic urethra
valve leaflets bladder and/or
bladder neck hypertrophy
diverticula narrow stream in the
penile urethra incomplete emptying
of the bladder
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Treatment of PUV:
Transurethral valve ablation, vesicostomy or upper tract diversion
Urethral stricture is a common complication
Fetal intervention carries a high risk with mortality rate of 43%
ESRD, renal insufficiency and chronic renal failure are long-term consequences
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30% of boys with posterior urethral valves whose symptoms present in infancy are at risk for progressive renal insufficiency.
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PUV, 2 months , MCU
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PUV, 2months
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Mcu done for suspected PUV
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9 months old child with dribbling of urine and difficulty in passing urine
?PUV MCU done Uroprophylaxis suggested Told by another Doc: not necessary Came with high grade fever after 1 month UTI
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Vesicoureteral Reflux Retrograde propulsion of urine into the upper
urinary tract during bladder contraction. Primary reflux is caused by attenuation of
the trigone and the contiguous intravesical ureteral musculature.
May be caused by the ectopic insertion of the ureter into the bladder wall resulting in a shorter intravesicular ureter, which acts as an incompetent valve during urination.
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The ratio of the submucosal tunnel length to the ureteral diameter is the primary factor determining the effectiveness of the normal valve mechanism.
It is normally 5:1, and in those with reflux it is 1.4:1.
The intramural length increases from 0.5 cm at birth to 1.3 cm by 12 years of age.
Duplication of the collecting system and ureteroceles should also be considered.
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Some clinical facts about VUR:
It is genetic. Occurs in about 30% of first-degree
relatives. 1/3 of children with a urinary tract
infection has reflux on VCUG. Primary reflux tends to resolve over
time as intravesical segment elongates with growth.
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Grading of Vesicoureteral Reflux
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VUR Grading
Grade I Grade II Grade III
Grade IV Grade V
Prognosis - 5% adultsScarring - 5-50%ScreeningUTI
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Prognosis: Resolves
spontaneously before adolescence in: 90% of Gr. 1 reflux 80% of Gr. 2 50% of Gr. 3 10% of Gr. 4 0 in Grade 5 reflux
Kidney is most susceptible to scarring in the first year of life and at the time of first upper tract infection.
Scars less frequently develop after the age of 5.
VUR and scarring lead to hypertension, progressive renal insufficiency and failure.
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Treatment:
Observation Medical treatment of infections Surgical treatment
significant hydroureteronephrosis indicated if impossible to keep urine
sterile and reflux persists acute pyelonephritis occurs evidence of increasing renal damage
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VUR
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MCU
C/o Recurrent UTI
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Management of VUR I-III (IV)-V conservative operative UTI neurogenic bladder scar duplex system non-compl. Solitary kidney transplanted kidney
? pontaneous resolution STING / SMING neoimplantation
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Endoscopic submucosal injection
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Endoscopic submucosal injection
• Teflon• Silicon• Collagen
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Bacterial virulence Virulence=factors that enable bacteria to
invade the urinary tract Surface antigenes
O: lipopolysacharides with endotoxin properties. Induces fever, local inflammation
K, (capsular) antigene, prevents phagocytosis
“P” fimbriae: bind to glycolipid receptors of the P blood group family
A number of further factors not routinely checked
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Bacterial virulence
Pyelonephritis: 3-4 (known) virulence factors
Cystitis: 0-2 factors
CAVE: OBSTURCTION !! MALFORMATION !!