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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