Every year, approximately 50,000 infants are born who are under 32 weeks in gestational age and who weigh less than 1,500 g

The Child with Urinary Tract Infection
Henrietta Kotlus Rosenberg, MD, FACR, FAAP
Englewood, New Jersey, USA


Urinary tract infection (UTI) is a common problem in infants and children. The symptoms of UTI may at times be nebulous, as patients may present with fever, nonspecific abdominal or pelvic pain, back pain, nausea, vomiting, irritability, loss of continence, new onset of bedwetting, hematuria, foul smelling urine, and/or failure to thrive. Radiologic imaging serves to detect those structural and functional abnormalities of the urinary tract that predispose the child to UTI, including vesicoureteral reflux (VUR), upper urinary tract obstruction (ureteropelvic junction obstruction [UPJ]), lower urinary tract obstruction (primary megaureter, ureterovesical junction obstruction [UVJ], posterior urethral valve, ectopic ureterocele with or without associated duplex collecting system), neurogenic problems (dysfunctional voiding), calculi, and parenchymal scars. Rapid diagnosis and differentiation between upper (pyelonephritis) and lower (cystitis) UTI, and immediate institution of appropriate treatment is essential to minimize renal damage. Facts About Urinary Tract Infections in Children
Numerous factors predispose the child’s urinary tract to infection. The increased virulence of certain strains of bacteria can contribute to the development of UTI in some children. P fimbriae Escherichia coli adhere to urothelial cells and cause slow flow in the peripheral ureters so that adherent bacteria are not washed away. This bacterium secretes endotoxins that cross the ureteral mucosa and gain access into the muscle, leading to paralysis of ureteral peristalsis and risk of ascent and reflux of bacteria. Other uncommon organisms include Klebsiella, Proteus, Pseudomonas, and Enterobacter. Compromise of host natural immune defenses that protect the urinary tract from infection also predisposes pediatric patients to development of UTI. In addition, some children have colonization of their feces by virulent bacteria. Urinary tract infections are more likely to occur in girls because of the ease of introital contamination and resultant bacterial access to the bladder. There is 10-times higher incidence of UTI in uncircumcised boys than in those who are circumcised. In addition, the normal unidirectional brisk flow of urine that serves to wash away unattached bacteria from the urinary tract is compromised in the presence of VUR, obstruction, and/or incomplete bladder emptying. Before an imaging work-up is begun, there must be laboratory confirmation of a UTI. The diagnosis of UTI is based on a properly collected specimen. In the infant or child without urinary control, specimens should be obtained via sterile catheterization or, when necessary, by suprapubic aspiration. In patients with urinary control, a clean-catch midstream specimen is generally sufficient for diagnosis (>100,000 colony count). The primary role of imaging in the evaluation of UTI in the pediatric age range is to detect structural abnormalities which predispose the infant, child, or adolescent to a UTI, and to demonstrate resultant damage to the urinary tract. Renal size, renal growth (serial sonograms), and renal texture must be evaluated and a careful assessment for parenchymal scarring must be performed. One must look for congenital and acquired causes of obstruction of the kidneys, ureters, bladder and urethra, VUR, intrarenal reflux, and bladder wall abnormalities. The most commonly used imaging modalities used for these purposes are renal sonography (ultrasound [US], fluoroscopic voiding cystourethrogram (VCUG), nuclear voiding cystourethrogram (NVCUG), and nuclear renal scintigraphy including diuretic renography as needed. The excretory urogram is no longer recommended in the routine evaluation of childhood UTI, as information regarding anatomy and function can be better assessed with US and nuclear renal scintigraphy, modalities that provide less radiation exposure and avoid the potential risk of iodinated contrast allergy. While US offers better anatomic detail of the kidneys and bladder, nuclear renal scintigraphy provides quantitative and qualitative analysis of renal function and aids in the assessment of urinary tract obstruction. Computed tomography (CT) and magnetic resonance imaging (MRI) are primarily reserved for complex cases in which a definitive diagnosis cannot be made with routine imaging. Henrietta Kotlus Rosenberg, MD, FACR, FAAP
The Child with Urinary Tract Infection
Ultrasound, the modality of choice for screening the urinary tract in infants and children is not dependent on renal function and does not involve radiation. Ultrasound evaluation should include the entire urinary tract: kidneys (size, contour, echotexture, scars), bladder capacity (BC) (BC = length x depth x width/2, wall thickness, wall contour), distal ureters, postvoid residual, collecting systems (include ureters if dilated), and urethra (without voiding or if indicated with voiding). The addition of duplex, color, or power Doppler imaging is useful to demonstrate areas of decreased perfusion in patients with focal or diffuse areas of pyelonephritis and to differentiate dilated ureters from vascular structures. The sonographic examination of the urinary tract should begin with the examination of the bladder in order to obtain images prior to involuntary voiding by pediatric patients who are not yet potty trained. If the bladder is empty or inadvertently empties, the baby or toddler can be given an appropriate amount of liquid to drink to allow for filling of the bladder while the upper tracts are being scanned. The normal bladder capacity can be estimated as follows: < 1 year, BC (cc) = weight (kg) x 7; > 1 year, BC (cc) = age (years) + 2 x 30. In newborns, the BC should be 30-50 cc; at 1 year, 100 cc; at 5 years, 200 cc; at 10 years, 300 cc. The disadvantages of US that have been noted include decreased sensitivity for detection of acute pyelonephritis, inability to quantitatively assess renal function, difficulty in demonstrating small cortical scars, and difficulty in detecting ureteral stones and fungal balls in the absence of hydronephrosis. Voiding Cystourethrogram
Voiding cystourethrography is traditionally the first radiographic study performed in a child with a documented UTI. The procedure consists of a preliminary plain film of the abdomen and pelvis,
sterile catheterization of the bladder, filling and voiding films, and a postvoid kidney ultrasound
biopsy. In boys with a tight phimosis, the external genitalia are cleansed and a “blind” catheterization
is performed. In girls with labial adhesions, the adhesions need to be medically lysed with Premarin for
appropriate visualization of the urethra. During this procedure, assessment includes bladder capacity,
bladder wall thickness and contour, observation for VUR during maximal distention and micturition,
examination of the urethra, and measurement of the postvoid residual. This study allows for detection
of VUR that may put the kidneys at risk for scars developing. Urologists agree with radiologists that
initial voiding cystourethrography in males should be performed with digital fluoroscopic VCUG.
There is controversy as to whether NVCUG vs. VCUG should be the first study in girls less than 5
years of age. Some urologists feel the lower radiation dose afforded by NVCUG and the incidence of
urethra and bladder anomalies in girls outweighs the inability of NVCUG to consistently identify grade
1 VUR and accurately grade VUR using the International Reflux Study criteria. Others disagree and
advocate fluoroscopic VCUG initially, with subsequent NVCUG for follow-up studies. The presenter
believes that VCUG performed on modern digital equipment with careful attention to maximum
reduction of fluoroscopic imaging time can keep the radiation dosage to a bare minimum. Ultrasound
VCUG is used at some centers as an alternative first study in girls, using US contrast agents to identify
VUR. In boys, VCUG is necessary in order to evaluate the urethra for such problems such as posterior
urethral valve, stricture, or anterior urethral diverticulum. In females older than 5 years who present
with a first UTI, sonography is recommended and if the examination is normal, no further imaging is
necessary. If the sonogram is abnormal, VCUG is recommended and if that is normal, nor further
imaging is done. If the VCUG is abnormal, a nuclear renal scan is done. In the female who is older
than 12 years who presents with UTI, treatment and watchful waiting is recommended. If resolution
occurs with antibiotic treatment, imaging is not recommended. If, however, the patient experiences
recurrent UTI (2-3 episodes within 12-18 months), sonography is recommended. If the US is normal,
no further imaging is necessary, but if the sonogram is abnormal, VCUG is recommended.

Nuclear Renal Scintigraphy

A wide selection of technetium 99mTc-labeled radiopharmaceuticals are available to evaluate the kidneys. Each agent is primarily chosen for its ability to evaluate specific aspects of renal function. Using 99mTc-labeled agents, such as DTPA and MAG3, dynamic imaging of the kidneys can be obtained. Time activity curves are useful to quantify renal function, including: renal perfusion, Henrietta Kotlus Rosenberg, MD, FACR, FAAP
The Child with Urinary Tract Infection
glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and tubular transit times. The post-Lasix diuretic renogram is useful for determining high-grade renal obstruction. Cortical imaging agents such as GHP, DMSA, and MAG3 can assess the renal parenchyma for morphologic anormalities such as scars or congenital anomalies. Excretory urogram, CT, and MRI are reserved for complex cases in which the anatomic details cannot be completely delineated with conventional modalities such as US, VCUG, or nuclear medicine. CT and MRI have proven to be excellent for demonstration of complications of pyelonephritis, such as intrarenal abscess, perinephric abscess, and perinephric fluid collections, particularly when contrast-enhanced. Some researchers are advocating MRI for the anatomic and functional diagnosis of urinary tract obstruction. Cost factors and need for sedation or anesthesia must be considered. Vesicoureteral Reflux
Vesicoureteral reflux tends to occur in families, with an incidence of reflux in 8% to 26% of the siblings of the index child, thus suggesting that screening of siblings may be advisable. Grading of VUR is based on the International Reflux Study Classification. The underlying anatomic cause for reflux is presumed to be an abnormal insertion of the distal ureter at the UVJ. In some females with reflux, the ureter is postulated to insert into the bladder musculature surrounding it to function as a sphincter. This abnormal angle of insertions diminishes as a young girl grows, making spontaneous resolution of reflux likely with time. The same phenomenon is not seen in boys because of the presence of the prostate gland and other anatomic differences. Secondary reflux can develop in infants and children because of diverticulum at the UVJ (Hutch diverticulum), dysfunctional voiding secondary to a neurogenic bladder, and bladder-sphincter dyssynergy. When VUR reflux is demonstrated and is of a degree that requires prophylactic low dose antibiotics (usually grade II or higher), followup imaging (VCUG or NVCUG) is obtained one year after initiation of treatment to determine if the reflux has resolved and (US of entire urinary tract) to determine if the kidneys demonstrate appropriate serial growth, if there is evidence of parenchymal scarring, and if there is hydro(uretero)nephrosis. If the reflux is worsening and kidneys are not growing satisfactorily or demonstrate worse scarring, it may be necessary to correct the reflux either with ureteral reimplantation or with endoscopic treatment with injection of autologous chondrocytes at the ureterovesical junction. Congenital Anomalies
Differentiation between upper and lower urinary tract anomalies is essential. Arbitrarily, the author defines the upper tract to include the kidney down to the level of the UVJ, ureteral duplication (complete, incomplete) including reflux into the collecting system of the lower pole or obstruction of the upper pole with or without ureterocele, ureteral obstruction (atresia, kink), and UVJ. Lower tract anomalies include neurogenic bladder, bladder and urethral diverticula, bladder dyssynergia, posterior urethral valves, anterior urethral valve, phimosis, and bladder and/or urethral fistula. Calculi, although rare, may be the underlying cause of UTI. Ultrasound evaluation of patients with UTI should include a thorough search for stones, especially in the presence of urinary tract obstruction and difficulty voiding. The entire urinary tract should be scanned, including the urethra. No enhanced spiral CT is reserved for patients with negative sonograms and a high clinical suspicion of calculi, although in large or obese patients, CT is the modality of choice. Imaging the Kidneys in Pyelonephritis
Imaging the kidneys in patients with pyelonephritis with sonography may be challenging, but early diagnosis is essential to better avoid renal damage. Pyelonephritis results from ascending infection, hematogenous spread, or VUR, and must be accurately diagnosed and distinguished from uncomplicated lower UTI. Clinical symptoms may include flank pain, fever, nausea, vomiting, and Henrietta Kotlus Rosenberg, MD, FACR, FAAP
The Child with Urinary Tract Infection
malaise. Most patients present for screening US. In acute pyelonephritis, the kidneys may appear sonographically normal. Abnormal findings may be subtle but should be meticulously looked for, such as renomegaly, decreased cortico-medullary differentiation, focal parenchymal abnormalities, decreased color Doppler flow, and thickening of the walls of the renal collecting systems (>0.8 mm). In chronic pyelonephritis, scars and decreased renal size may be demonstrated. In acute pyelonephritis, renal nuclear scan using DMSA, GHP 99mTc, or MAG3 is useful to demonstrate focal renal parenchymal defects or a flare pattern of decreased activity from the hilum of the kidney to the periphery. With chronic pyelonephritis, focal defects and decreased renal size may be seen. Computed tomography and MRI are usually not necessary for the diagnosis of acute or chronic pyelonephritis. With acute pyelonephritis, these modalities may demonstrate renomegaly, focal areas of decreased contrast enhancement of perinephric stranding, whereas with chronic inflammation, scars and decreased renal size may be noted. These modalities are useful for the detection of complications such as intrarenal or perinephric abscess and perinephric fluid collections. Pyonephrosis/Fungal Infection
Ultrasound is useful for the demonstration of echogenic material within the collecting systems in the presence of bacterial or fungal infection. Although the finding of echogenic urine is not specific for a particular cause, the possibility of fungal infection should be considered in pediatric patients with immune e suppression or with diabetes mellitus. Hydronephrosis and renal bezoars (fungal balls caused by Candida albicans) may result from systemic candidiasis in low-birth premature neonates. Lower Urinary Tract Infection: Cystitis
Most females with UTI have acute cystitis. Symptomatology includes dysuria, urgency, frequency, hesitancy, lower abdominal/pelvic pain, new onset urinary incontinence and/or bed wetting, strong foul smelling urine, and hematuria. Although US findings may be normal, at times, the bladder wall is thickened (focal or diffuse), particularly with viral (hemorrhagic) cystitis. With viral cystitis, the bladder wall may have characteristics more suggestive of rhabdomyosarcoma (mass-like wall thickening, bullae), but the history differentiates cystitis from tumor and US findings resolve within 2 weeks. Patients with hemorrhagic cystitis present with acute urinary frequency, dysuria, and hematuria, whereas patients with tumors are more likely to present with hematuria and signs of urinary tract obstruction. Other Conditions Mimicking Cystitis
Other conditions may predispose or simulate cystitis. These include neurogenic bladder, urachal diverticulum, and bladder wall diverticulum or diverticula, focal bladder wall thickening caused by indwelling catheter, prostatitis, and tumor. In summary, pediatric patients with UTI need rapid diagnosis and differentiation between upper and lower UTI so that appropriate therapy can be instituted promptly and renal damage minimized. Henrietta Kotlus Rosenberg, MD, FACR, FAAP
The Child with Urinary Tract Infection
1. Rosenberg HK, Ilaslan H, Finkelstein MS. Work-up of urinary tract infection in infants and
children. Ultrasound Quarterly 2001;17:87-102. 2. Rosenbaum DM, Korngold E, Teele RL. Sonographic assessment of renal length in normal children. AJR Am J Roentgenol 1984;142:467-9. 3. Kenda RB, Novljan G, Kenig A, Hojker S, Fettich JJ. Echo-enhanced ultrasound voiding cystography in children: a new approach. Pediatric Nephrology 2000;14:297-300. 4. Paltiel HJ, Diamond DA, Zurakowski D, Drubach LA, Atala A. Endoscopic treatment of vesicoureteral reflux with autologous chondrocytes: postoperative sonographic features. Radiology 2004;232:390-397

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Pii: s0891-5849(99)00247-6

Free Radical Biology & Medicine, Vol. 28, No. 3, pp. 351–360, 2000Copyright © 2000 Elsevier Science Inc. PII S0891-5849(99)00247-6 Original Contribution INCREASED LIPOPROTEIN OXIDATION IN ALZHEIMER’S DISEASESVEN SCHIPPLING,* ANATOL KONTUSH,* S¨ONKE ARLT,* CARSTEN BUHMANN,† HANS-J¨ORG ST¨URENBURG,†ULRIKE MANN,‡ TOMAS M¨ULLER-THOMSEN,‡ and ULRIKE BEISIEGEL**Medi


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