Urinary tract infections, renal malformations and scarring Yaacov Frishberg, MD Division of Pediatric Nephrology Shaare Zedek Medical Center Jerusalem, ISRAEL
UTI - definitions UTI = growth of bacteria within the urinary tract (heterogeneous group) Symptomatic UTI Acute pyelonephritis (renal parenchyma - fever) Acute cystitis (lower urinary tract dysuria) Unspecified UTI manage as acute PN Asymptomatic bacteriuria
When should you suspect urinary tract infection? Neonatal fever (following circumcision) Anorexia, vomiting and lethargy in infancy Fever of unknown etiology ( weakness, loss of appetite and vomiting) Abdominal pain Dysuria, frequency Secondary enuresis
UTI - epidemiology 6.6% of girls and 1.8% of boys had had symptomatic UTI by the age of 7 years 43% of the affected girls and 60% of the boys had febrile UTI The highest incidence was during infancy Gender difference in the incidence of firsttime infection beyond the age of 2 years Early detection and prompt treatment Acta Paediatr 87:549-52,1998
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UTI - pathogenesis Beyond the neonatal period ascending infection Periurethral bacterial flora urethral length in females voiding pattern in boys Bacterial properties adherence to uro-epithelial cells (E. Coli pili) inflammatory response (Toll-like receptor recruitment, IL-6, IL-8, neutrophils recruitment) Defense mechanisms of the bladder (emptying)
Acute pyelonephritis clinical presentation High fever >38.5 0 C Back or loin pain (>4-5 years) Renal tenderness Elevated CRP or ESR Leukocytosis Low serum sodium In the newborn non-specific signs (apathy, anorexia, vomiting, greyish color)
Acute pyelonephritis Pay special attention if: History reveals heredity for urinary malformations Previous episodes of unexplained fever Abdominal mass Back anomaly suggestive of spinal dysraphism High blood pressure
Acute cystitis clinical presentation Voiding symptoms (dysuria, frequency, urgency) Afebrile or low grade fever (<38.5 0 C) Check genital area for local inflammation (especially in girls)
UTI diagnosis Urinalysis: pyuria (casts), nitrite test (requires long bladder time or significant residual), hematuria, bacteriuria Urinalysis cannot substitute for urine culture Frequent culturing of urine in febrile children is necessary in order to have a high detection rate Urine culture should be obtained before treatment is started
Urine culture The quality of the urine sample is essential sample refrigerated dipslide (colonies of different types, agar) suprapubic puncture (any count) catheterization of the bladder (10 3-10 4 ) voided sample: midstream or bag (10 5 ) very high false-positive rate!
Bacteria causing first time UTI in children < 2 years E. coli is the most common bacterial cause (85%) Other gram negative: Klebsiella, Proteus, Enterobacter, Citrobacter Gram positive bacteria: Staph saprophyticus, enterococcus, Staph aureus Non-E. Coli UTI is associated with urinary tract anomalies, young age and previous antibacterial therapy
UTI - treatment Children with symptomatic UTI should be given antibiotics without delay Resistance pattern of urinary pathogens in the area Recent antibacterial treatment Persisting growth indicates bacterial resistance or severe abnormality in urinary tract
Antibacterial drugs in childhood UTI agent sensitivity Amoxicillin 30-40% Trimetoprim-sulfamethoxasole 65-70% 1 st gen cephalosporines 65-70% 2 nd gen cephalosporines 80-90% Nalidixic acid 80-90% Nitrofurantoin 80-90% I.V.: ampicillin/gentamicin, cefuroxime
UTI - resolution Sterile urine within 1-2 days Afebrile within 4-5 days A check-up urine culture at the end of the treatment period is unnecessary Later samples should be obtained ONLY if the child develops symptoms suggestive of UTI
First time pyelonephritis Complete 10-14 days of antimicrobial therapy Refer child for a renal-bladder ultrasound If ultrasound abnormal consider further imaging studies (VCUG; DMSA scan)
Ultrasonography Lack of clinical response within 2 days of antimicrobial therapy to rule out: Obstruction Localized infection (nephronia, abscess) Kidneys: size, position, echotexture, scarring, hydronephrosis, double collecting system, dilated ureters Bladder: hypertrophy, dilation of distal ureters, ureterocoele Normal US does not exclude vesicoureteric reflux
Recurrent UTI s 8-30% will experience recurrent episode(s) of febrile UTI Start prophylactic antibiotics controversial Evaluate and treat bowel and bladder dysfunction Refer child to a pediatric nephrologist Imaging studies (US, VCUG, DMSA scan) Long term follow-up
Bowel and bladder dysfunction An abnormal elimination pattern Frequent or infrequent voids Urgency Constipation Bladder and/or bowel incontinence Withholding maneuvers
Bowel and bladder dysfunction 20% of children with UTI s are likely to have bladder dysfunction Treatment reduces the likelihood of recurrent UTI s Treatment is associated with faster resolution of VUR
Treatment of bladder dysfunction Timed voiding (every 2-3 hours) Double voiding Avoidance of C s: carbonated drinks, caffeine, citrus, chocolate and food colorants Consider another C: cranberry juice Use laxatives for constipation
Vesicoureteral reflux (VUR) The rate of VUR among children younger than 1 year with UTI exceeds 50% VUR occurs in ~1/3 of all children examined after UTI Grades of severity based on the extent of the reflux and associated dilatation of the ureter and pelvis Children with high grade VUR are 4-6 times more likely to have scarring than those with low-grade VUR (and 8-10 times more than those without VUR)
UTI s, reflux and scarring Reflux in combination with upper UTI can be dangerous to the kidney Reflux without UTI has not been shown to be dangerous Upper UTI without demonstrable reflux can cause renal damage Unilateral renal damage carries some risk for longterm complications Bilateral damage is associated with considerable risk for long-term complications (hypertension and decreased renal function)
Voiding cystourethrography - VCUG VCUG with fluoroscopy characterizes reflux better than does radionucleide cystography (RNC) There is no benefit in delaying performance of these studies as long as the child is free of infection While waiting for reflux study results the child should be receiving antibiotics therapy
Reflux grade at first VCUG Grade Boys (n=183) Girls (n=505) 0 126 (68.8%) 332 (65.7%) I 8 (4.4%) 36 ( 7.1%) II 31 (16.9%) 101 (20.0%) III 14 (7.6%) 33 (6.5%) IV 2 (1.1%) 2 (0.4%) V 2 (1.1%) 1 (0.2%)
Imaging of renal scarring 99m Tc-DMSA renal scintigraphy has by and large replaced the IVP for detection of scarring Localizes in the proximal tubular cells with minimal excretion The preferred method for visualizing functioning renal parenchyma Quantitative assessment of differential renal function
Risk factors for renal scarring Congenital vs. acquired Reflux with dilatation Young age Delay of treatment Number of pyelonephritic attacks Obstruction Unusual bacteria
Renal scarring The process of scarring is slow (up to 2 yrs) Occurs in 10-15% Increased risk of recurrent UTI, hypertension and renal failure In pregnant women: recurrent UTI, pregnancy-induced hypertension, preeclampsia and renal failure
Outcome of scarred kidneys 30 patients (26 females) 27 years after the detection of pyelonephritic scarring The mean age of scarring detection - 6 years No follow-up 3 developed ESRD and the remaining had a significantly low GFR than 13 healthy control subjects BMJ 1989;299:703-6
Long-term follow-up of renal function in children with UTI Follow-up investigation 16-26 yrs after the first recognized UTI Overall GFR was well preserved and low risk of hypertension A significant reduction of individual renal GFR in the unilaterally scarred kidneys Concomitant decrease in the incidence of ESRD due to pyelonephritic scarring High awareness of UTI in infants and close supervision of those with renal scarring may minimize deteriorating renal function Arch Pediatr Adolesc Med 2000;154:339-345
Asymptomatic bacteriuria More common in girls Prevalence of 1.2%-1.8% in schoolchildren Treatment may increase the risk of complications: elimination of bacteria of low virulence may result in recurrences in 80% Antibacterial treatment may result in acute pyelonephritis Voiding dysfunction should be ruled out
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