Infection is the most common abnormality of the urinary system in children. The urinary tract is the second most common site of bacterial infections in children, after the respiratory tract. Although most urinary tract infections are relatively minor and respond promptly to appropriate treatment, chronic or recurrent infections can lead to severe, even life-threatening, complications such as hypertension and end-stage renal disease. Of urinary tract infections, those of the kidneys carry the greatest risk of clinically significant sequelae.

Urinary tract infections can involve the renal parenchyma, collecting system, bladder (cystitis), or urethra (urethritis). The commonly utilized term pyelonephritis indicates infection or inflammation of both the renal parenchyma and the pelvicaliceal system. Additional categories of kidney infections include diffuse pyelonephritis, focal pyelonephritis, renal abscess, pyonephrosis, perirenal abscess, and retroperitoneal abscess. Unless complicated by pyelonephritis, infectious cystitis is rarely associated with long-term sequelae.

Screening studies have demonstrated bacteriuria in 1% to 1.4% of all neonates.^1–3 At this age, urinary tract infections are more common in males than in females. Uncircumcised infant boys are 8 to 10 times more likely to have a symptomatic urinary tract infection than circumcised boys.⁴ In preschool- and school-age children, bacteriuria is more prevalent in girls.^5,6 The female-to-male ratio of urinary tract infection is 0.4:1 in the neonatal period, 1.5:1 at the age of 1 to 6 months, 4:1 at 6 to 12 months, 10:1 at 1 to 3 years, 9:1 at 3 to 11 years, and 2:1 at 11 to 16 years.⁷ Once treated, infants with symptomatic urinary tract infection have about a 25% risk for recurrent infection, usually within the first 3 months. In older girls, the risk for recurrence within 18 months is as high as 40% to 60%; this elevated risk persists into adulthood.⁵

The clinical manifestations of urinary tract infections tend to vary with patient age. In neonates, nonspecific systemic symptoms are common; bacteremia develops in 30% to 40%, and progression to life-threatening sepsis can occur. Urinary tract infections in infants beyond the neonatal period also frequently result in nonspecific systemic symptoms such as fever and abdominal pain. However, sepsis is much less frequent at this age than in neonates; bacteremia occurs in less than 20% of these children.

Dysuria is common in preschool- and school-age children with urinary tract infection. Other potential clinical manifestations include abdominal pain, flank pain, enuresis, and fever. Systemic symptoms are typically absent or less severe in this age group than in infants. Although the clinical presentation frequently points toward urinary tract involvement, a specific diagnosis is not always possible on clinical grounds alone. There are multiple potential causes of dysuria, including vaginitis, urethritis, and cystitis. Urine bacteria counts may be relatively low despite the presence of a bacterial urinary tract infection.

Teenagers with urinary tract infection tend to have a more straightforward clinical presentation than do infants. Flank pain and dysuria are common. However, accurate differentiation between isolated lower urinary tract involvement and infections involving the pelvicaliceal system and kidney is unreliable when based on the clinical manifestations alone. In addition, sexually active teenage girls with the urinary frequency–dysuria syndrome can present with findings that overlap those of urinary tract infection.

The clinical diagnosis of bacterial urinary tract infection can be established when a substantial number of a single species of bacteria is cultured from the urine. The most commonly utilized definition of clinically significant bacteriuria is the growth of more than 100,000 colonies of a single organism/mL of urine obtained by a clean-catch technique, that is, greater than 100,000 colony-forming units. When the urine is collected by catheterization or suprapubic puncture, growth of fewer than 100,000 colonies/mL is usually abnormal. The 2011 criteria for the diagnosis of a bacterial urinary tract infection recommended by a Clinical Practice Guideline from the American Academy of Pediatric are urinalysis with pyuria or bacteriuria and urine culture with pure growth of at least 50,000 colony-forming units/mL. Microscopic evaluation of urine for leukocytes (≥ 5 WBCs/HPF) and dipstick evaluation for urine nitrites and leukocyte esterase are also diagnostically useful.⁸

Clinical criteria are inaccurate for the diagnosis of acute pyelonephritis. Suggestive findings include fever, culture-proven urinary tract infection, and elevation of C-reactive protein or the erythrocyte sedimentation rate. Imaging studies show evidence of parenchymal renal infection in 35% to 70% of children with a febrile urinary tract infection. Bladder washout studies and ureteral catheterization studies have demonstrated bacteria in the pelvicaliceal systems of as many as 20% of children with bacterial cystitis who lack clinical manifestations of upper tract involvement; these children are likely at risk for renal damage. Therefore, diagnostic imaging studies serve an important role for the detection of upper tract involvement in selected patients.⁹

Bacterial urinary tract infections most often involve organisms common in the fecal flora, such as Escherichia coli (80%), Proteus species (usually in association with urolithiasis), and Staphylococcus species (particularly in boys). P-fimbriated strains of E. coli are commonly associated with renal parenchymal infections, whereas these organisms account for less than one-fourth of instances of cystitis. Approximately 70% of upper urinary tract infections are caused by E. coli species with capsular polysaccharide antigen types 1, 2, 3, 12, and 13. Other pathogens include Klebsiella spp., Enterobacter, Serratia, Enterococcus, and group B streptococci. Candida infections are important in immunocompromised patients. Adenovirus can cause hemorrhagic cystitis.^10,11

Bacterial infection of the kidney most often occurs in the form of pyelonephritis due to ascension of organisms from the bladder. This is postulated most often to occur by way of reflux of infected urine, hence the importance of vesicoureteral reflux in the pathophysiology of upper urinary tract infections. Passage of organisms via subepithelial lymphatic channels from the bladder and ureter into the renal interstitium represents an additional potential pathway. Hematogenous inoculation of the kidney can also occur; this can lead to renal infection in the absence of bacteriuria. The hematogenous pathway is more common in infants than in older children, and more frequently involves staphylococcal species.

At least half of instances of acute pyelonephritis occur in the absence of substantial vesicoureteral reflux. However, vesicoureteral reflux is associated with a definite increased risk for pyelonephritis and parenchymal scarring. A history of a prior episode of pyelonephritis is an additional risk factor for future episodes.

Approximately 40% of children with renal parenchymal infection develop some degree of scarring. Scarring of moderate or marked severity can lead to hypertension; the onset is frequently delayed until adulthood. Hypertension is present in approximately 10% to 25% of young adults with substantial renal scarring related to childhood disease. The mild scarring that occurs in most children with vesicoureteral reflux or acute pyelonephritis is associated with little or no measurable risk for secondary hypertension. Clinically obvious renal insufficiency as an acute or delayed consequence of pyelonephritis is rare, except in children with severe preexisting renal abnormalities. Laboratory evidence of long-term compromise of renal function is more common, particularly when there is evidence of substantial bilateral scarring.¹²

Renal scarring is the most important manifestation of clinically significant kidney damage in patients with urinary tract infection and/or vesicoureteral reflux. There are 3 major proposed mechanisms for the occurrence of renal scarring in association with vesicoureteral reflux: (1) the parenchymal thinning in some patients represents dysplastic tissue due to abnormal embryological development of the ureteral bud. The developmental alteration concomitantly causes vesicoureteral reflux. (2) The episodes of reflux of sterile urine may lead to renal damage, possibly through an immunological mechanism. However, animal studies have failed to document renal scarring due to sterile high-pressure reflux alone. (3) Inflammatory destruction and fibrosis of renal parenchyma can result from passage of infected urine into renal papillae. This appears to be the most common mechanism of renal scarring.

The kidneys contain both simple and compound papillae. The simple form is a conical papilla that is resistant to intrarenal reflux because the orifices of the collecting ducts are slit-like and the collecting ducts follow oblique courses as they enter the calyx. As pressure within the calyx increases, the distal portions of the collecting ducts tend to collapse and thereby resist intrarenal reflux. A compound papilla contains more than 1 pyramid at its tip. The central pyramids of a compound papilla are less resistant to intrarenal reflux than those of simple papillae because their collecting ducts open into the calyx at right angles to the flat portion of papillae. The common occurrence of compound papillae in the polar regions of the kidneys may, at least in part, account for the propensity for scarring in these areas. The greatest risk for intrarenal reflux and reflux-associated renal damage is during infancy and early childhood; intrarenal reflux is an uncommon finding on cystourethrography in children over the age of 6 years. Likewise, renal scarring is predominantly the result of infections that occur during the first 2 to 4 years of life; infections in older children are unlikely to lead to scarring.

Followup diagnostic imaging studies are usually indicated for all infants and toddlers after their first urinary tract infection. The recommendations for imaging of older children are the subject of considerable attention and debate. The most commonly utilized studies for this indication are voiding cystourethrography (VCUG) and sonography. The most recent guidelines from the American Academy of Pediatrics Committee on Quality Improvement (2011 revision) recommend against routine performance of a VCUG after the first UTI. VCUG is recommended for children who have (1) sonographic evidence of hydronephrosis, scarring, or other findings that suggest high-grade VUR or obstructive uropathy, (2) atypical or complex clinical circumstances, or (3) recurrence of a febrile UTI.⁸

Cystourethrography allows the accurate detection and characterization of vesicoureteral reflux, as well as the demonstration of an underlying developmental or acquired abnormality of the lower urinary tract or ureter (e.g., urinary tract obstruction, ureterocele, posterior urethral valve, or bladder wall abnormality). Sonography serves to assess the upper urinary tract for scarring and predisposing developmental lesions such as duplication or obstruction. Although sufficient for most patients, renal sonography is less sensitive than renal cortical scintigraphy, CT, or MR for the demonstration of renal scarring.^13,14 Renal cortical scintigraphy (usually performed with ^99mTc-dimercaptosuccinic acid [DMSA]) has a sensitivity of 96% and a specificity of 98% for the detection of renal scarring. After sonography, this is the most commonly utilized imaging study selected for this indication.^15,16 MR is reported to provide a sensitivity of 77% to 84% and a specificity of 86% to 87% for the detection of renal scarring.^17,18

The imaging studies noted above are generally utilized for followup of children who experience a clinically diagnosed urinary tract infection, and are best performed a few weeks after resolution of symptoms. However, the presence of an infection does not affect the propensity for vesicoureteral reflux; therefore, a VCUG can be performed during treatment of an infection. Imaging of the kidneys during an acute illness is indicated in selected patients to detect renal parenchymal involvement and complications of infection. Effective imaging techniques for the evaluation of acute renal infection include sonography, CT, scintigraphy, and MRI.^16,19–21

Acute bacterial pyelonephritis can occur in children of all ages. Common presenting signs and symptoms include fever, chills, and flank pain. In some children, there is palpable fullness in the flank due to enlargement of the kidney. Progression of infection to renal abscess or perinephric abscess can occur.

The pathophysiology of acute bacterial pyelonephritis includes infiltration of the involved renal parenchyma with leukocytes, interstitial and cellular edema, and vasoconstriction of small vessels in the area of infection. Pus may accumulate in the collecting tubules. Permanent renal damage can occur due to inflammatory destruction of renal tubules and local ischemia.²²

Grayscale sonography of acute pyelonephritis without suppuration may show focal or diffuse parenchymal swelling, abnormal parenchymal echogenicity, and loss of corticomedullary differentiation (Figure 47-1). Edematous urothelium may appear thickened on sonography (Figure 47-2). A small amount of perinephric fluid is occasionally present. Standard sonography is normal in up to half of patients with uncomplicated pyelonephritis. Doppler sonography utilizing power and color techniques improves the sensitivity of ultrasound for the diagnosis of pyelonephritis; reported sensitivities range from 63% to 89% (Figure 47-3). This technique allows detection of perfusion defects due to infection-induced vasoconstriction (Figure 47-4). The sensitivity of sonography for the detection of acute pyelonephritis is increased with the use of a contrast-enhanced technique; foci of infection appear as triangular areas of subnormal perfusion.^23–26

Focal pyelonephritis confined to 1 or more renal lobules is sometimes termed “lobar nephronia.” The resultant local area of swelling and abnormal echogenicity sometimes has the sonographic appearance of a small mass, with a bulge in the renal contour (Figure 47-5). Echogenicity of the inflamed portion of the kidney varies between patients, and can be hypoechoic, isoechoic, or hyperechoic; however, loss of normal corticomedullary differentiation is a universal finding. Typically, the interface between inflamed and normal parenchyma is somewhat ill-defined. Patients with substantial focal renal enlargement should have followup imaging studies to exclude a neoplasm.

The scintigraphic evaluation of acute renal infection is usually performed with ^99mTc-DMSA; gluceptate is an alternative agent. Single-photon emission computed tomography (SPECT) images increase the anatomic detail of the examination. The infected portions of the kidney have diminished or absent accumulation of radiopharmaceutical, often with a spherical or flare-like pattern (Figure 47-6). These agents bind to the proximal renal tubular epithelial cells. Uptake of tracer with these imaging studies requires both perfusion and renal tubular secretion. The defective uptake in the presence of infection may predominantly be due to a metabolic alteration in the transport mechanism in the tubular cell membrane. Local vasoconstriction and inflammatory obstruction of capillaries are additional important mechanisms.^27,28

Scintigraphy may continue to show a parenchymal defect for several months following an episode of pyelonephritis. Ditchfield et al reported that 44% of children with acute pyelonephritis had persistent scintigraphic defects between 2 and 6 months after the initial scan; however, only 18% still had defects on scintigraphy performed 23 to 26 months after the first scan.²⁹ Agras et al found residual uptake defects in 38% of patients on scintigraphy performed 6 months after the initial infection and 18% at 12 months.³⁰ Therefore, definitive scintigraphic evidence of scarring requires that a defect persist for at lease several months.

^99mTc scintigraphy with DMSA detects acute pyelonephritis with sensitivity and specificities of greater than 90%. An overall 94% agreement has been reported between DMSA imaging and histopathological findings for the detection of individual segmental lesions.²⁸ An animal study comparing the various available imaging techniques showed DMSA SPECT scintigraphy to offer the highest sensitivity and specificity for the detection of pyelonephritis. The sensitivities and specificities in this study were 92% and 94% for DMSA SPECT, 90% and 88% for MR, 87% and 88% for CT, and 74% and 57% for sonography.³¹

CT is a sensitive method for the detection of acute renal infection, and is the superior technique for the characterization of complications such as an intrarenal or perinephric abscess. Inflammatory edema and microabscesses alter the tissue attenuation characteristics of the infected kidney, sometimes visible as subtle regions of subnormal attenuation on unenhanced CT images. Local or global nephromegaly is common. The major CT finding, however, is diminished attenuation on contrast-enhanced images. This is due to local vasoconstriction and inflammation, which interfere with contrast excretion in the infected parenchyma. Various patterns can occur on enhanced images: (1) radially oriented linear streaks of decreased attenuation, (2) round or irregular hypoattenuating foci, (3) wedge-shaped defects (Figure 47-7), and (4) heterogeneous poor enhancement throughout an enlarged kidney (Figure 47-8). The nephrogram of the involved kidney is often diminished in intensity. Delayed images frequently show coarse “staining” of the involved parenchyma due to retention of contrast in obstructed pus-filled tubules visualized against a background of normal parenchyma in which appropriate clearance has occurred; this is a relatively specific characteristic of renal infection on CT (Figures 47-9 and 47-10).

Edema from acute infection causes diminished signal intensity on T1-weighted MR images and increased signal intensity on T2-weighted images. The involved parenchyma often appears expanded. There may be loss of corticomedullary differentiation and/or a striated appearance of the parenchyma. Stranding of fat within the perinephric space is common. In some patients, the Gerota fascia appears thickening and irregular. Contrast-enhanced images are quite helpful when there is suspected renal infection; vasospasm and debris within collecting tubules result in deficient enhancement in the involved portions of the parenchyma. A focus that completely lacks internal enhancement suggests the presence of an abscess. With pyonephrosis, there is layering of hypointense pus in the contrast-enhanced collecting system.^32,33

Although IV urography provides excellent definition of renal collecting system morphology, it is of little use for the detection of renal infection. Other imaging techniques, including sonography, renal cortical scintigraphy, contrast-enhanced CT, and MR, are much more sensitive for the diagnosis of acute pyelonephritis than is IV urography. Because IV urography provides only limited information about renal function, this technique shows manifestations of renal infection in only approximately 20% of affected children. Potential findings include a delayed nephrogram, nephromegaly, delayed appearance of contrast in the pelvicaliceal system, and slow emptying of contrast from the pelvicaliceal system and ureter (diminished ureteral peristalsis).

Scintigraphy with gallium-67 or ^99mTc-labeled white blood cells serves a complementary role to standard imaging techniques for patients with renal infection. Most often, selection of these studies is to survey the entire body of the patient who has evidence of infectious disease but no localizing signs. Radiogallium and labeled white blood cells avidly accumulate within an infected kidney (Figure 47-11).³⁴

Acute renal infection can lead to renal scarring. The pathophysiology involves renal parenchymal necrosis due to infection-related influx of leukocytes, release of cytotoxic metabolites, and local vasoconstriction (ischemia). This complication may be more common in those patients with superimposed vesicoureteral reflux, but many patients who develop scars do not have demonstrable reflux. Although scarring due to renal infection is most common in infants and young children, children of all ages with pyelonephritis are at substantial risk for progression to scarring.³⁵ Up to 10% of children with substantial renal scarring eventually develop end-stage renal disease during adulthood and at least 20% develop hypertension.^36,37

Sonography is the most commonly utilized technique to detect scarring in patients following pyelonephritis (Figure 47-12). However, renal cortical scintigraphy provides greater sensitivity, and is the preferred technique in many institutions (see image 48-4).^38,39 Scars are often best appreciated on SPECT images. MRI is also is sensitive for the detection of renal scaring. Fat-saturated T1-weighted and contrast-enhanced short tau inversion recovery (STIR) images are often most helpful. MR can be useful for the differentiation between postinfection scarring, congenital dysplastic parenchymal thinning (small kidney with dysmorphic calyces and abnormal parenchyma), and renal hypoplasia.^18,40