URINARY TRACT INFECTIONS
Presented by
Sarfraz Ahmed Ansari
Under guidance of
Dr.Chandrakanta (MD)Deptt.Of Paediatrics; CSMMU; Lucknow
Overview Background Epidemiology Etiology Clinical features Diagnosis Treatment Follow up Prevention Imaging Vesico-ureteral reflux (VUR) Summary
BackgroundUrinary tract infection (UTI) is common in infants and
childrenUTI is difficult to recogniseCollecting urine and interpreting laboratory results is not
easyDiagnosis is not always confirmedUTI in infants and children may have long term sequelae UTI due to ESBL produces ranging uncomplicated
infection to life threatening sepsis emerging very fast.
Management of it differ altogether.
Importance of UTI
Acute morbidity
Urological disorders
VUR (30-40%)
obstructive uropathy (5%)
VUR
UTI
ScarReflux nephropathy
Hypertension & ESRD
UTI- Infection of urinary tract identified by growth of a significant number of organism of a single species in urine in the presence of symptoms.
Significant bacteriuria – Midstream urine sample showing colony count >105/ ml of a single organism. Any bacterial growth in specimen by SPA
Symptomatic UTI-- significant bacteriuria with symptoms like dysuria frequency & urgency with or without fever & renal or flank pain.
Definitions
Asymptomatic Bacteriuria—significant bacteriuria on 2 or > specimen in a child without symptoms (Incidence 1-2 % preschool age girls ,0.03% boys) No treatment except in pregnent women & following instrumentationComplicated UTI—UTI with presence of fever >38.50c ,toxic look, vomiting, dehydration & renal angle tenderness
Simple UTI –UTI with low grade fever, dysuria,frequency,urgency but none of the symptoms of toxemia
Definitions contd..
Atypical UTI seriously ill, poor urine flow, abdominal or bladder mass, raised creatinine, septicaemia, failure to respond to treatment with suitable antibiotics within 48 hours or infection with non-E. Coli organisms.
Recurrent UTI two or more episodes of UTI with acute pyelonephritis/upper UTI, or one episode of UTI with acute pyelonephritis/upper UTI plus one or more episodes of UTI with cystitis/lower UTI, or three or more episodes of UTI with cystitis/lower urinary tract infection.
Definitions contd..
NICE 2007
Epidemiology
Prevalence of UTI Girls 3-5%, first UTI by 5 years (peak -infancy, toilet training)
-In 60-80% 2nd UTI within 18 months-In Boys-mostly during 1st year of life.-Much more common uncircimcised males
Boys 1%, most UTIs during the first year of life During infancy
Male : female :: 2.8-5.4 : 1 Beyond 1-2 years of age
Male : female :: 1: 10
Hellerstein’s Ped Clin. North Am 1995;42 ;1437-1457IPNG INDIAN Pediatrics 2001;38:1106-1115IJP-2009.76(8):809-814.
Urinary Tract InfectionEpidemiology (N=990)
Age group Total(Males) “Upper tract”
“Lower tract”
0-1 years
38(66%) 35(92%)
3(8%)
1-4 years
570(24%) 242(42%)
328(58%)
≥5 years
382(22%) 127(33%)
255(67%)
Total 990(25%) 404(41%)
586(59%)Christian MT et. al. Arch Dis. Child. 2000;82:376
Incidence of Renal Scarring
Population based study in Sweden - 9.3/ lac with ratio girls : boys- 2 : 1 -0.18% girls & .11% boys in population –Renal Parenchymal defect. Systemic review 4 prospective studies -5-15% children have Renal parenchymal defects (Dick PT et al . Journal of paed. 1996;128 (1) :15-22)
―Mainly by colonic bacteria―E.coli( 75- 90 %) ―Klebsiella spp.―Proteus spp―Proteus =E.coli < 1yrs boys―Grm.+ve organism – males―Staph. Saprophyticus & Enterococci in both―Viral infection –sp. Adenovirus—cystitis―Proteus & pseudomonas—Recurrent UTI, instrumentation & Nosocomial infection.―Fungi— immunocompromised―Candida albicans—common in preterms immunocompromised & prolonged antibiotic therapy.
Etiology
Risk factors for UTI
Female gender Uncircumcised male VUR Toilet training Voiding dysfunction Obstructive uropathy Urethral
instrumentation Bubble bath
Tight clothingPinworm infestationConstipationBacteria with p.fimbriaeAnatomic abnormality (labial adhesion)Wiping from back to front in femaleNeuropathic bladderSexual activityPregnancyBroad spectrum antibiotics for minor infections
Nelson text book of paediatrics
Usually ascending infection
Haematogenous –Endocarditis & some neonates
Pathogenesis
mannose resistans mannose sensitive
Flagellum
Capsular k-1 Antigen
Fimbriae Type2 Type1
Haemolysin Aerobactin
Type I fimbriae-Mannose sensitive -no role in UTI
Adhesion-Glycocalyx polymers -Biofilm formation
Adhesion-Activation of cytokines-Adhesin molecues & Chemotaxis
O antigen (LPS, Endotoxin) of E.coli- inflammation & fever
Urothelial cells--Glycosphingolipid --- Gal—1—4 gal receptor
Age group Symptoms and signs
Most common Least common
Infants younger than 3 months
FeverVomitingLethargyIrritability
Poor feedingFailure to thrive
Abdominal painJaundiceHaematuriaOffensive urine
Infants andchildren,3 months orOlder
Preverbal Fever Abdominal painLoin tendernessVomitingPoor feeding
LethargyIrritabilityHaematuriaOffensive urineFailure to thrive
Verbal FrequencyDysuria
Dysfunctional voidingChanges to continenceAbdominal painLoin tenderness
FeverMalaiseVomitingHaematuriaOffensive urineCloudy urine
Lower UTI or cystitis-urgency, dysuriafrequency,
suprapubic pain, incontinence & malodorous urine -fever is not common -common in females -less chance of associated anomalies.
Difficult to distinguish upper UTI & lower UTI in infants & children <5 yrs.(Mehta KR Ali U. (under IAP subsp. Series on Paed.infectious disease (underIAP action Plan 2006) 1st edn 2006; 178-183.
Upper UTI / Acute pyelonephritis-Fever ,vomiting,toxemia ,flank pain (occasionally diarrhoea) -In new borns poor feeding, irritability & wt loss.
-usually associated with urinary tract malformations
Upper & lower UTI
Classical signs and symptoms – urgency, frequency and dysuria may not be presentSymptoms are non-specific – irritability, anorexia, failure to gain weight, vomiting, diarrhea, feverThus delay in diagnosis of acute pyelonephritis likelyHigh index of suspicion of UTI essential as:
UTI is the commonest bacterial infection in febrile infants and young children without an obvious cause.
Younger child is at greatest risk for renal damage if treatment is delayed
Diagnosis
History and examination–Poor urine flow or dysfunctional voiding–Previously suggested or confirmed UTI–Recurrent fever of uncertain origin–Antenatally diagnosed renal abnormality –Family history of vesico-ureteric reflux or renal disease–Constipation–Dysfunctional voiding–Enlarged bladder–Abdominal mass–Evidence of spinal lesion–Poor growth–High blood pressure
Sample collection
Supra pubic aspiration -Gold standard for obtaining urine in infant -Invasive (should be avoided -NICE 2007) -Risk of contamination is very low
-2cm. above syphysis gentle negative Pressure while advancing the needle.
-Complications rare if USG guided -Any growth – diagnostic
Clean catch midstream specimen -In toilet trained children -Most widely used -Can be easily performed -Ramage et al. demonstrated strong correlation with sample from SPA -Recommended method by NICE 2007
Cathetrised specimen.Temporary catheterisation or from indwelling catheterUrine aspirated from catheter by using sterile needle & syringeVery reliable method, fewer contamination
Colletion bag—not recommended (AAP-1999)
Adhesively attached to perineal areaHigh contamination rateFalse positivity very highUnneccessary testing & hospitalisationNo role in diagnosis of childhood UTIIf negative rules out UTI
Mild proteinuria leukocytouria (leukocytosis>5/hpf(spun) or >10/mm3(unspun) Centrifugation of urine 10 ml, spun @5000 rpm for 5 min Bacteriuria UTI can occur in absence of pyuria.. Pyuria can be present without UTI. Normal urinalysis in asymptomatic child excludes UTI. Symptomatic child –UA negative -UTI possible.
UrinalysisMicroscopy & Dipstick tests
Leukocyte EsteraseLE is produced from the breakdown of
leukocytes. Not always indicative of infectionVaginitis/vulvitis can lead to inflammation without
infection + LEHas to accumulate in urineInsufficient accumulation possible in small
infants who void frequentlyInfants <3 months old may not have mature
enough immune system to induce leukocytes in urine
Nitrites or Greiss’ test
Nitrites are produced by bacteria that metabolize nitrates: E. coli, Klebsiella, Proteus (GNRs)
Much more predictive of UTIGPCs do not produce nitrites
By products of E. coli and other lactose fermenters 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)
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, nitrite ,Microscopy 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)
AAP 1999
Urine culture is necessary for confirmation & appropriate therapy
Method of collection Colony count (pure culture) Probability of infection Suprapubic aspiration Gram-negative bacilli: any
number Gram-positive cocci: > a few thousand
>99%
Transurethral catheterization >105 95%
104 to 105 Infection likely 103 to 104 Suspicious; repeat <103 Infection unlikely
Clean void Boy: >104 Infection likely Girl: 3 specimens >=105 95% 2 specimens >=105 90% 1 specimen >=105 80% 5 x 104 to 105 Suspicious; repeat 104 to 5 x 104 Symptomatic: suspicious;
repeat Asymptomatic: infection unlikely
<104 Infection unlikely
Hellerstein S. Recurrent urinary tract infections in children. Pediatr Infect Dis 1982;1:271-81.
Criteria for the Diagnosis of Urinary Tract Infection
Other Tests CBC—leukocytosis,Neutrophilia ESR raisedCRP increased Blood culture (neonates & infants) (Garin et al, pediatrics Nephr . 2007;22;1002-1006) Specific gravity-- renal concentrating capcity decreased in Pyelonephritis (Winsberg S.et al Pead.1959;48;577-589) Antibody coated bacteria in urine detected by fluorescin -labelled antiimmunoglobin diagnostic of pyelonephritis in adolescents & young adults (Bensman et al, Arch fr. Pediatrics 1978;35:242-252)
Unreliable in children (hellerstein et al, j.paediatrics 1978;92:188-193) High procalcitonin in serum -ac.pyelonephritis in febrile UTI. ( Smolkin et al. pediatric Nephr 2002;17:409-412)
Imaging
Renal USG
Detects structural malformations Hydronephrosis Pyonephrosis & perinephric abscess Pyelonephritis-focal or diffuse enlargement Renal scars-hypoechoic Helpful in detecting the ureteral dilatation of advanced stage reflux (Grades III-IV)
Can be done immediately
Enlarged kidney
Hydronephrosis
Scarring
VCUG
Bladder is fully filled via catheter with radiopaque liquidChild is asked to voidDuring voiding, look under fluoroscopy for refluxCan be done after 48 hrs of receiving antibioticsCan be done 4 – 6 weeks after UTI
Two techniques– One involves fluoroscopic contrast – more
radiation but better delineation of anatomy for grading VUR
– The other uses a radionuclide – less radiation and more sensitive than contrast
Normal VCUG
Vesicoureteral reflux (VUR)
USG MCU USG + MCU
Sensitivity % 29.1 74.5 76.4
Specificity % 95.6 82.2 79.4
PPV % 41.0 30.4 27.8
NPV % 92.8 96.9 97.0
Imaging in Pediatric Urinary Tract InfectionPredicting Renal Scarring
AJR 2009; 192:1253–1260
Renal cortical scintigraphy DMSA SCANDifficult to distinguish between new acute inflammatory changes and stablished renal scarsMetaanalysis of animal studies –sensitivity -86% & specificity – 91%. (CRAIG JC et al, J.nucl.med.2000;41:986-993)
Only recmmonded by NICE clinical guidelines 2007Only where to confirm or exclude ac. Pyelonephritis & power doppler USG is not available.
Scar in the superior and inferior pole of the right
kidney
CT scan
Contrast enhancement d/t renal ischemia.Normal perenchyma brighter.Disadvantages-significant radiation exposer.Hypersensitivity to iodinated contrastSedationRarely used
Darkening of normal renal parenchyma. Brighter areas of pyelonephritis. D/A- cost, need for sedation IV gadolinium in renal insufficiency. (stean H et al. paed Nephr.2007;22:1239-1242)Lack of ionising radiation is appealing in pediatric age
MRI
Additional Investigations
An X-ray of the spine– spinal abnormalities if clinically
suspected.
X-ray KUB region --- calculi.
IVP may be performed to examine for renal scarring if
facilities for renal scintigraphy are not available.
TREATMENT
Treatment Based on Severity
Complicated
Age <3 months
Septicemia
Upper UTI
Toxic, vomiting
Uncomplicated
Older children
Not toxic
Accepting orally
IV, later oral Oral agents
Infants < 2-3 months with febrile UTIOlder infants and children with complicated UTIHigh fever and clinically ill or ‘toxic’Persistent vomitingModerate to severe dehydrationPoor compliance anticipated Renal angle tenderness.
Hospitalization recommended in:
Treatment contd…
The efficacy of oral regimens is as effective as parenteral regimens
If the child is not responding the empiric treatment within two days while awaiting culture results, repeat the urine culture and perform a renal ultrasound.
Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, Majd M, et al. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics 1999;104:79-86.
Baker PC, Nelson DS, Schunk JE. The addition of ceftriaxone to oral therapy does not improve outcome in febrile children with urinary tract infections. Arch Pediatr Adolesc Med 2001;155:135-9.
Parenteral Oral
Medication mg/kg/day Doses/day Medication mg/kg/day Doses/day
Ampicillin 100 3 Amoxicillin 30-35 3
Gentamicin 5-6 2 Cotriomoxazole 6-10
(trimethoprim) 2
Amikacin 15-20 2 Cephalexin 50-70 3
Cefotaxime 100-150 3 Co-amoxiclav 30-35
(amoxicillin)2-3
Ceftriaxone 75-100 1-2 Cefaclor 40 3
Ciprofloxacin 10-20 2
Cefixime 8-10 IPNG 2001
Antimicrobials for Treatment of UTI
Duration of therapy
Complicated UTI 10-14 d
Uncomplicated UTI 7-10 d
Shorter courses 3-4 d
lower tract infection [Cochrane 2003]
UTI caused by ESBL producing organisms
Klebsiella pneumoniae, E.coli, Proteus mirabilis, enterobacterWidespread use of 3rd generation cephalosporins is the major causeIn a study in JNMC Hospital Aligarh India, 42% isolates were ESBL producers in the community acquired UTIPoor response to 3rd generation cephalosporin and also resistant to Aminoglycosides & FluoroquinolonesConfirm ESBL producing status on culture & sensitivity pattern
AntibioticsPiperaacillin-tazobactum, Cefoperzone-sulbactum, Imipenem, Meropenem, Ertapenem, Faropenem, Cefepime
Urine Culture on follow up Urine cultures need not be routinely repeated at
cessation of antibiotic therapy.
A culture should however be obtained in patients
-Who fail to show the expected response to the treatment
-Recurrence of symptoms suggestive of a UTI
-Initial culture contaminated
Antibiotic prophylaxis
Controversial
Indications and Duration of Prophylaxis
Antibiotic prophylaxis is recommended under the following circumstances:1. Following treatment of: (i) First UTI in all children below 2 years of age, and (ii) complicated UTI in children below 5 years old, while awaiting
imaging studies.2. Children with VUR.3. Patients showing renal scars following a UTI even if reflux is not demonstrated. Prophylaxis may be stopped if a radionuclide cystogram or MCU repeated 6 months later is normal.4. Children with frequent febrile UTI (3 or more episodes in a year) even if the urinary tract is normal Not recommended in patients with urinary tract obstruction (e.g., PUV), urolithiasis or neurogenic bladder. chance of colonization with resistant organisms. IPNG 2001
Duration of prophylaxis Evidence is not conclusive, it appears the risk of
scarring diminishes with age. Some experts recommend cessation of
prophylaxis after age 5 to 7 years, even if low-grade VUR persists.
In one study of 51 low-risk (no voiding abnormalities or renal scarring) older children (mean age 8.6 years) with grades I to IV VUR, cessation of prophylactic antibiotics resulted in no new renal scarring on annual DMSA
Cooper CS, et al. The outcome of stopping prophylactic antibiotics in older children with vesicoureteral reflux. J Urol 2000 Jan;163(1):269-72; discussion 272-3.
Finding Age of patient Duration
First UTI
Reflux Next Table
No reflux but renal scar All Six months and re-evaluate*
No reflux, no renal scar <2 years Six months and re-evaluate*
>2 Years No prophylaxis
Recurrent UTI (Without reflux or scar)
All Six months
Indications and Duration for Antimicrobial Prophylaxis
IPNG 2001
* DRCG/MCU to look for reflux, which might have been missed on initial evaluation.Prophylaxis is stopped if reflux is not detected.
Grade of reflux Initial evalution Follow up
Grade I and II Antibiotic prophylaxis till 5 years of age
Grade III and unilateral Grade IV
Antibiotic prophylaxis below 5 years Surgery above 5 years
Surgery beyond 5 years if reflux persists at same grade
Grade IV (bilateral) and Grade V
Antibiotic prophylaxis below 1 year, Surgery above 1 year
Surgery if reflux persists at same grade
Treatment of Primary Vesicoureteric Reflux
IPNG 2001
Drug mg/kg/day Remarks
Cotrimoxazole 1-2 (trimethoprim) Avoid in infants <3 months age and G-6 PD deficiency.
Nitrofurantoin 1-2 GI upset; avoid in infants <3 months age, G-6 PD deficiency and renal insufficiency. Resistance rare
Cephalexin 10 Drug of choice in first 3-6 mo
Cefadroxil 3-5
Used in young infants where NFT & cotrimoxazole is restricted
Cefaclor 5-10
Cefixime 2
Antimicrobials for Prophylaxis of UTI
ABP should not be routinely recommended in infants and children following first UTI.ABP may be considered in infants and children with recurrent UTI.Asymptomatic bacteriuria in infants and children should not be treated with prophylactic antibiotics.
NICE Clinical guideline 2007
Antibiotic prophylaxis
Antibiotic prophylaxis
In the Indian ContextAntibiotic prophylaxis following UTI does not appear to prevent recurrence of infection and/or renal scarring in children with or without VUR, considered separately. Antibiotic prophylaxis could result in increased risk of recurrence with resistant organisms.Antibiotic Prophylaxis Following Urinary Tract Infection in Children: A
Systematic Review of Randomized Controlled Trials
Joseph L MathewAdvanced Pediatrics Centre, PGIMER, Chandigarh
Indian Pediatr 2010;47: 599-605
Does Circumcision Prevent UTI
Bacteria colonize urethral meatus
Uncircumcised 7-14/1000 Circumcised 1-2/1000 Relative risk: 4-10 fold Benefits limited to first year
Not an indication for routine circumcision
Baby boys with severe VUR or other renal anomalies at risk of UTI Arch Dis Child 2005;90:853-858)
Circumcision is not recommended routinely but may be considered for infants with recurrent UTI Attention to under-garments and perineal hygiene, including the foreskin in boys, is explained to the parents. Plenty of fluid intake and frequent voiding ensures flushing out of the uropathogens. Constipation predisposes to recurrent UTI and improvement in bowel habits reduces the incidence of UTI In children with VUR who are toilet trained, regular and volitional low pressure voiding with complete bladder emptying is encouraged Double voiding is recommended in order to empty the bladder of post void residual urine
Measures to Reduce Recurrent UTI
IMAGING
AAP (PEDIATRICS Vol.103 No.4 April 1999)
<2Years with UTI
Antimicrobial therapy
Response
YesNo
USG
VCUG or RNC
USG &VCUG or RNC
48 hrs 48 hrs
Evaluation following first documented UTI
First UTI
Ultrasound examination
Normal Abnormal
<2 years 2-5 years >5 years All ages
MCU and DMSA scan
DMSA scan MCU if: Scar on scan or scan -nt
No further evaluation
MCU and DMSA scan
IAP 2001Recurrent UTI , any age, USG & MCU, Renal scan for scar
Recommended imaging schedule
Responds well to treatment within 48 hours
Atypical UTI Recurrent UTI
Test
<6 Mths
6 Mths-3 yrs
>3 Yrs
<6 Mths
6 Mths-3 yrs
>3 Yrs
<6 Mths
6 Mths-3 yrs
>3 Yrs
Ultrasound during the acute infection
No No No Yesb Yesb Yesb,d Yes No No
Ultrasound within 6 weeks
Yesa No No No No No No Yes Yesd
DMSA 4–6 months following the acute infection
No No No Yes Yes No Yes Yes Yes
MCUG No No No Yes Noc No Yes Noc No
National Institute For Health And Clinical Excellence (2007)
In atypical UTI, USG of the urinary tract during the acute infection to identify structural abnormalities of the urinary tract e.g. obstruction For infants < 6 months with first-time UTI that responds to treatment, USG should be carried out within 6 weeks of the UTIFor 6 months or older with first-time UTI that responds to treatment, routine USG is not recommended except atypical UTIInfants and children with a lower UTI should undergo USG (within 6 weeks) only if they are < 6 months or have had recurrent infections.
A DMSA scan 4–6 months following the acute infection should be used to detect renal parenchymal defects In subsequent UTI while awaiting DMSA, the timing of the DMSA should be reviewed and consideration given to doing it sooner.
Imaging tests
Recommended imaging schedule
• a-If abnormal consider MCUG.• b-In an infant or child with a non-E. coli UTI, responding well
to antibiotics and with no other features of atypical infection, the ultrasound can be requested on a non-urgent basis to take place within 6 weeks.
• c-While MCUG should not be performed routinely it should be considered if the following features are present:
• dilatation on ultrasound
• poor urine flow
• non-E. coli infection
• family history of VUR.
• d-Ultrasound in toilet-trained children should be performed with a full bladder with an estimate of bladder volume before and after micturition.
Imaging Protocols Following First UTI
Ultrasound MCU DMSA
National Institute Of Health & Clinical Excellence (2007)
Indian Pediatric Nephrology Group (2001)
All 2 yr <5 yr
American Academy of Pediatrics (1999)
<2 yr <2 yr No guideline
Royal College of Physicians London (1991)
All <1 yr 1-7 yr
IPNG: US, VCUG & DMSA if any abnormalityAAP: Recommendations for <2 yr-old only
Newer studies
255 children < 5 years old admitted with their first uncomplicated febrile UTI
Renal ultrasound did not change management
Zamir G, Sakran W, Horowitz Y, Koren A, Miron D. Urinary tract infection: is there a need for routine renal ultrasonography? Arch Dis Child 2004;89:466-8
Newer studies
150 children 2 – 10 years old with first UTI were randomized to routine imaging (U/S and VCUG) or to selective imaging (for recurrent UTI or persistent problems)
21 % (1 in 5) in the selective group had imaging performed
Routine imaging increased the use of prophylactic antibiotics (28% vs 5%)
No change in rate of recurrent UTIs (26% vs 21%) No change in rate of renal scarring (9% vs 9%)
Dick PT. Annual Meeting of Canadian Pediatric Society, June 12-16, 2002. Pediatric Notes 2002;26(27):105
Vesicoureteric reflux (VUR)
Vesicoureteral Reflux
Approximately 40% of children with febrile UTIs have VUR.
Approximately 8% of children with febrile UTIs demonstrate renal scarring when studied.
Treatment recommendations are made to stop the progression of VUR with medications/antibiotics and/or surgery.
No data demonstrate that treatment of VUR prevents renal scarring, hypertension and CKD
Nuutinen M, Uhari M. Recurrence and follow-up after urinary tract infection under the age of 1 year. Pediatr Nephrol 2001;16:69-72
Vesicoureteric Reflux Grading
“Antenatally diagnosed hydroureteronephrosis with postnatal conformation of
Dilatoing VUR often shows renal scarring on DMSA before any UTI has occurred.
This is renal dysplasia and accounts for a significant proportion of the renal damage
seen in dilating VUR”
IJP 2009; 76(10):1031-1035
Renal scarring
Congenital dysplasia
Global damage
Hypertension, renal
failure
Boys with VUR IV-V
Not amenable to therapy
Acquired scarring
Small scars
Limited long term
morbidity
Girls: recurrent UTI
May be prevented
Renal ScarringDysembryogenesis vs. Infection
VUR
The management of VUR is evolving and the final word is yet to
be said
(Dave s et al. Indian j urology 2007: 23:403-413)
Principles of management VUR can cause upper UTI by bringing
bacteria to the kidneysResults: renal scarring, loss of
parenchyma reflux nephropathy:Potential for hypertension, decreased renal
function, proteinuria, renal failure/ end stage renal disease
Management: based on -Identification of children with VURPrevention of renal damage due to reflux
GRADE AGE (YR) SCARRINGINITIAL TREATMENT FOLLOW-UP
I–II Any Yes/No Antibiotic prophylaxis
No consensus
III–IV 0–5 Yes/No Antibiotic prophylaxis
Surgery
III–IV 6–10 Yes/No Unilateral:antibiotic prophylaxis
Surgery
Bilateral:surgery
V <1 Yes/No Antibiotic prophylaxis
Surgery
V 1–5 No Unilateral:antibiotic prophylaxis
Surgery
V 1–5 No Bilateral:surgery
V 1–5 Yes Surgery V 6–10 Yes/No Surgery
Summary of guidelines developed by American Urological Association;age refers to age at diagnosis
Treatment Recommendations for Vesicoureteral RefluxDiagnosed Following a Urinary Tract Infection
Concerns about medical therapy
Long-term antibiotics may complications: minor to severe - including bone marrow suppression,
Stevens-Johnson syndromeAdherence (compliance)Breakthrough infection Urine-analysis and cultures whenever UTI
possibleSurveillance cultures at 3-4 monthsNeed to monitor reflux with either VCUG or
radionuclide cystography (RNC), both with discomfort and radiation
VUR TREATMENT
Medical vs surgical therapyNot clearMeta–analysis Wheeler, et al. (Arch Dis Child 2003; 88:688-594)7 randomized, controlled studies,ABP vs surgery, n = 859
4 studies: no difference after 5 years2 studies: less febrile UTI, at 5 years, surgery
(10%) vs ABP (22%)But no difference in scarring!
Meta-analysis, continued4 studies: no differences in scarring after 5
years5% overall risk of new scars by DMSA
4 studies: no differences in renal growth2 studies: no difference in hypertension or
end-stage renal diseaseNo information about surgical vs medical
adverse events
Meta-analysis, continued
conclusions 9 reimplantations required to prevent 1 febrile UTI No reduction in rate of renal scarring! Hardly seems wise to prefer surgical therapy
Vesico-ureteric refluxAim of treatment is to prevent further scarringNo difference in outcome between surgical and
Medical intervention (International Reflux Study in Children, European Branch. J Urol 1992;148:1666 Birmingham Reflux Study Group. BMJ 1987;295:237-241)
Surgical correctionSTING (Macroplastique,defflux)Ureteric reimplantaion
VUR: indications for surgery
Parental preference, poor compliance, intolerance to medical treatment
Possible role Breakthrough UTI
New scarring
Persistent grade V reflux beyond infancy
Reflux with nephropathy, reduced GFR
“It is not clear whether any intervention for children with primary VUR does more good than harm. Well designed and adequately powered placebo controlled randomized trials of antibiotics alone in children with
VUR are now required.”
(Wheeler et al, Antibiotics and surgery for VUR: a meta-analysis of RCTs, ADC, 2003)
Clinical Trials
Author, Journal, Year Abx No Abx RR (95% CI)
Savage, Lancet, 1975 7/29 (24%) 4/32 (13%) 1.9 (0.6-5.9)
Garin, Pediatrics, 2006 13/55 (24%) 12/58 (21%) 1.1 (0.6-2.3)
Roussey, JU, 2008 18/103 (17%) 32/122 (26%) 0.7 (0.4-1.1)
Garin: Up to age 18 years, febrile UTI, grades 1-3 VUR, unblinded
Roussey: 1 mo – 3 years, febrile UTI, grades 1-3 VUR, unblinded
In Garin study, recurrent acute pyelo seen in 7/55 (abx) v. 1/58 (placebo) (p=0.03) raising specter of INCREASED risk of APN with prophylactic antibiotics.
No. (%) with Recurrent UTI
Systematic Review
“The evidence to support the widespread use of antibiotics to prevent recurrent symptomatic UTI is weak. Large randomized, double blinded studies are needed…”
Williams et al, Long-term antibiotics for preventing recurrent UTIs in children. Cochrane Database of Systematic Reviews 2006, Issue 3.
Prophylaxis vs. None for VUR
No difference in risk of UTI, scarring(Reddy. Pediatrics Suppl 1997; RCT; 43 children; followed for 1 yr)
Similar UTI rates with/without prophylaxis(Georgaki-Angelaki. Scand J Infect Dis 2005)
Multicenter RCT; no difference in UTI rates, scars(Garin. Pediatrics 2006; 236 patients with/without VUR followed 1 yr)
More UTI with prophylaxis; no difference in scars(Peratoner. Ped Nephr ’06 ; 90 pts; followed 2 yr with/withoutprophylaxis)
Urine culture: standard for diagnosis
All patients with UTI need evaluation
No need for surveillance cultures
Current management of VUR might not result in reduction in ESRD
VUR: prophylaxis, surgery or nothing?
Summary
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