Chapter 86: Urinary Tract Diseases

• Signs and symptoms of urinary tract infection (UTI) may be nonspecific in young infants, and even older children may not complain of dysuria.

• In the evaluation of infants and children with fever without a source, up to 7% of patients will be found to have a UTI.

• Urinary catheterization is the method of choice for obtaining the urine specimen in febrile infants and young children.

• Presence of bacteria on a Gram stain or nitrites and leukocyte esterase on urine dipstick are highly indicative of a UTI, but urine culture is the gold standard for diagnosis.

• Greater than 5% of infants younger than 3 months with fever and UTI are bacteremic.

• Antibiotic choice for UTI must be guided by local resistance patterns and effectiveness against Escherichia Coli.

• Approximately 90% of renal stones are radiopaque and can be managed medically.

• Computed tomography (CT) scan of the abdomen without contrast is the test of choice for the evaluation of children with renal stones; however, ultrasound may be used to evaluate children with recurrent renal stones.

• Recurrence rates of urolithiasis are high in children and require a thorough metabolic evaluation for the cause.

Urinary tract infection (UTI) is a frequent cause of fever in infants and young children accounting for more than 1.1 million visits annually, and occurring in 2.4% to 2.8% of all children.^1,2 It is important to identify and treat UTIs because this may lead to the diagnosis of unsuspected anomalies of the urinary tract, and, thus, the prevention of morbidity associated with progression to pyelonephritis as well as long-term complications of renal scarring such as chronic renal failure and hypertension. Fever may be the sole manifestation of a UTI. Febrile children younger than 24 months with no other identifiable source for fever on examination were found to have a 7% probability of UTI (range <1%–16%), which is higher than the likelihood of occult bacteremia (<1%) among fully immunized children.^3,4 The prevalence of UTI varies with age and gender. Studies show a 2- to 3-fold higher risk of UTI in febrile, uncircumcised male infants than age-matched females and a 10-fold greater risk of UTI than circumcised males in the first 3 months of life.^4,5 After 3 months of age, febrile female infants have a higher prevalence (2%–10%) of UTIs compared to their male counterparts with circumcised males having less than a 0.5% chance of UTI after 6 months of age.⁴ Race may also play a role in the incidence of UTI with Whites showing a higher prevalence (8% vs. 2.7%) compared with African Americans.⁴

Classic symptoms of UTI such as dysuria, urgency, increased urinary frequency, and flank pain are less frequently reported in children than in adults.⁴ Young children, in particular, are more likely to present with nonspecific symptoms. It is important to identify common risk factors for UTI, which include age less than 12 months, white race, history of UTI, suprapubic tenderness, lack of a source for fever, fever greater than 39°C, and fever for more than 2 days.^3,7,8

Pathophysiology

The development of a UTI may be due to colonization of the urinary tract by bacteria, viruses, fungi, or parasites. Of these, bacteria are by far the most common etiology. Viruses, namely adenovirus and BK virus, commonly cause lower UTIs or hemorrhagic cystitis. Fungal UTIs tend to occur in immunocompromised patients or those on long-term antibiotic therapy.

In the setting of bacterial UTIs, bacteria enter the urinary tract by one of the three mechanisms: retrograde ascent of fecal-perineal bacteria, direct introduction of bacteria via instrumentation, or hematogenous spread in the setting of systemic illness. Retrograde ascent via the fecal-perineal route is the most common cause of UTI. Thus, Escherichia coli is responsible for more than 80% of UTIs in children. Other gram-negative organisms include Klebsiella spp., Proteus spp., Enterobacter, and Pseudomonas. The most common gram-positive pathogens include group B streptococci, Enterococcus spp., and Staphylococcus aureus.^4,9,10 The presence of S. aureus suggests a more invasive infection due to hematogenous spread from other sites such as abscess, osteomyelitis, or bacteremia. In otherwise healthy children, Lactobacillus spp., coagulase-negative staphylococci, and Corynebacterium spp. are generally not considered to be pathogens. E. coli and Staphylococcus saprophyticus are the most common organisms in sexually active females. Nosocomial infections and those associated with Foley catheterization are most often caused by E. coli, Candida albicans, and Pseudomonas aeruginosa.⁹

In young infants or immunocompromised children, UTIs can result from systemic seeding due to bacteremia. In infants between 29 and 60 days of age, the risk of concomitant bacteremia is 6.5%.¹¹ After 3 months of age, the risk of bacteremia in the setting of UTI drops to less than 5%.

The main defense mechanism against UTI is constant anterograde flow of urine from the kidneys with intermittent complete emptying of the bladder. Dysfunctional elimination or any obstruction to normal flow may predispose children to development of UTIs. Backflow of urine due to vesicoureteral reflux (VUR) can lead to recurrent UTIs, pyelonephritis, and renal scarring. Other predisposing factors for UTI include sexual intercourse, pregnancy, and diabetes mellitus. Urine and the mucosal wall of the collecting system have antimicrobial qualities.¹² Bacteria that cause UTIs, such as E. coli species, often exhibit distinctive virulence factors that overcome the normal host defenses.

Signs and Symptoms

UTIs are divided into two overlapping categories: lower UTIs are limited to cystitis and urethritis, whereas upper UTIs include ureteritis, pyelitis, and pyelonephritis.⁶ Signs and symptoms vary with the age of the patient and are often nonspecific in children younger than 2 years. It is important to identify known risk factors for UTI to help guide diagnostic evaluation in the young child.⁷ Neonates and infants younger than 3 months tend to have nonspecific symptoms with or without fever, including vomiting, diarrhea, lethargy or irritability, oliguria, poor feeding, or failure to thrive. Newborns may exhibit asymptomatic jaundice. Children younger than 2 years may exhibit fever, vomiting, or anorexia. Any child younger than 2 years requiring administration of an antibiotic for fever without a source, should undergo urinalysis including culture prior to antibiotic administration.¹³ Patients between 2 and 5 years of age may complain of fever and abdominal pain. In the older child, symptoms may become more specific, including dysuria, frequency, urgency, suprapubic discomfort, hematuria, and flank or back pain.¹²

A thorough history in the patient suspected of having a UTI may uncover dysfunctional voiding. Symptoms include infrequent or incomplete bladder emptying, withholding maneuvers, daytime urgency-frequency syndrome, and enuresis or incontinence. In some children, constipation represents an equivalent to dysuria.⁶ Abnormal elimination of bladder and bowel is an often overlooked factor in the pathophysiology of UTI, particularly in school-aged children.

Dysfunctional elimination is also a risk factor for VUR and renal scarring. Up to 40% of toilet-trained children with their first UTI and 80% of patients with recurrent UTIs have dysfunctional elimination.⁴ A recent systematic review showed that 57% of children with their first documented UTI have evidence of acute pyelonephritis on a renal cortical scan, and children with VUR were 1.5 times more likely than children without VUR to have such findings on the dimercaptosuccinic acid (DMSA) scan.¹⁴

Patients with abdominal or flank pain, high fever, vomiting, or other systemic signs must be evaluated for pyelonephritis. Fever may be the predominant symptom, often without dysuria, even in older children.⁶ Females have a trimodal-age distribution for UTI with highest rates occurring in the first year, at the time of toilet training, and when sexual activity begins. All children should have a genital examination, looking for vaginal or penile discharge or foreign bodies, epididymitis, orchitis, or anatomic abnormalities. Moreover, a UTI should be considered in all patients with serious illness even if there is evidence of other infection.

Diagnostic Evaluation

Urine culture from an adequate urine sample is the gold standard to establish the diagnosis of UTI. Urinalysis is often used concomitantly, and while the results can be helpful, they may also be misleading. The presence of leukocyte esterase and/or pyuria (>5 WBCs per high-power field) carries a sensitivity greater than 90%, however, the specificity is poor. Many other entities can cause pyuria including exercise, masturbation, appendicitis, gastroenteritis, acute glomerulonephritis, Kawasaki disease, vaginitis, and bubble bath soap. WBC casts are pathognomonic of pyelonephritis.⁵ The presence of urinary nitrites, produced by gram-negative enteric bacteria, is highly specific (>90%) for a UTI. Yet, caution should be taken in its absence, particularly in infants and children with frequent voiding habits as this cannot be used to rule out a UTI.¹³ The presence of bacteria on Gram stain of an uncentrifuged urine sample is perhaps the single best rapid indicator of infection with a positive likelihood ratio of 18.5 and a negative likelihood ratio of 0.07.¹⁵ Urine dipstick also serves as a reliable screening tool, particularly in well-appearing febrile infants without an obvious source. In children younger than 2 years, the presence of both leukocyte esterase and nitrites has a positive likelihood ratio of 12.6 and the absence of both carries a negative likelihood ratio of 0.13.¹⁵ In children older than 2 years, the urine dipstick may be even more reliable with a reported positive likelihood ratio of 38.54 when both are present.¹⁶

The American Academy of Pediatrics (AAP) supports monitoring the clinical course of children between 2 months and 2 years of age with a negative urinalysis result who are deemed low risk for a UTI or are otherwise well-appearing. Thus, a sterile urine specimen need not be obtained.¹³ However, if the results of urinalysis or urine dipstick testing are positive, a urine culture should be obtained to confirm and identify the source of infection in all pediatric-age groups. The most recent AAP guidelines recommend the diagnosis of UTI be made in children between 2 months and 2 years of age only in the presence of a positive urinalysis and greater than 50,000 colony forming units of a single uropathogenic organism on culture obtained via catheterization or suprapubic aspiration (SPA).¹³

Methods of obtaining a urine sample include “bagging” the perineum, a “clean-catch” of mid-stream urine, urinary tract catheterization, and SPA. Although bag collection is noninvasive, it is the least reliable method due to high false-positive rates. Screening for UTI with bagged urine is only useful if it is negative. If the urinalysis results are positive, a clean-catch or sterile urine specimen should be sent for culture; catheterization or SPA should be used if the child is younger than 2 years or not yet potty-trained. Catheterization is usually chosen over SPA as SPA is more painful. Regardless of which method is used, confirmation of sufficient bladder volume with bedside ultrasound improves the success rate.¹⁷ Complications of SPA are uncommon, but include hematuria, bowel perforation, cystitis, and abdominal wall hematoma or infection.¹⁸ Older children are usually able to provide an adequate mid-stream “clean-catch” specimen. See Figure 86-1 for recommended evaluation for diagnosing UTIs.

Electrolytes and renal function tests should be considered on all patients with signs of dehydration or toxicity as well as infants, males, and patients with signs of upper UTI. In addition, consideration should be given to obtaining a serum procalcitonin (PCT) level. Studies have shown elevated levels of PCT (>0.5 ng/mL) correlate well with renal parenchymal involvement and future development of renal scarring as identified on DMSA scinitgraphy.¹⁹

Management and Radiologic Evaluation of the Urinary Tract

Empiric antibiotic therapy for UTI is directed at the presumed infecting organism until results of the urine culture are obtained (Table 86-1). In general, oral outpatient therapy is effective for the management of uncomplicated UTIs. Antibiotic choice should be guided by local resistance patterns and include coverage of E. coli. In addition, special attention should be paid to an individual patient's history such as VUR, immunodeficiency, history of complicated UTI or unusual prior uropathogens. There is widespread resistance to ampicillin and amoxicillin, and resistance to trimethoprim-sulfamethoxazole (TMP-SMX) and resistance to first-generation cephalosporins is increasing.²⁰ Appropriate first-line agents include second- and third-generation cephalosporins. However, it is important to remember that cephalosporins will not cover infections due to Enterococcus species. Ciprofloxacin should not be used as a first-line agent in children due to adverse musculoskeletal events. It has, however, been approved by the FDA for use in children with complicated UTIs. For children younger than 2 years the total course of therapy should be 7 to 14 days.¹³ Older children with uncomplicated cystitis are usually treated for 5 to 7 days.

Children older than 6 years may benefit from the addition of phenazopyridine (Pyridium) for pain control. Pyridium can be given 10 mg/kg/din three divided doses for 2 to 3 days or until patients are less symptomatic.

Strongly consider admission for intravenous antibiotics in all infants younger than 2 months, infants with pyelonephritis, immunocompromised patients, those with known urinary tract obstruction, children unable to tolerate oral fluids or medications, and those with inadequate follow-up or unreliable caretakers. Criteria for admission are listed in Table 86-2. Intravenous antibiotic therapy should continue until blood culture results are negative and for a minimum of 24 hours after resolution of symptoms. ²⁰ Appropriate choices for first-line parenteral therapy vary by age and may include Ampicillin plus Gentamicin, Cefepime, Cefotaxime, Ceftriaxone, or Ciprofloxacin. ²⁰ Stable patients may be discharged on an appropriate oral antibiotic to complete a 7- to 14-day course. Complicated UTIs are usually treated for a minimum of 10 to 14 days; this includes male patients, children younger than 2 years, patients with recurrent UTIs, and all admitted patients.

Children younger than 2 years who are diagnosed with their first febrile UTI should be evaluated for urinary tract abnormalities with a renal-bladder ultrasound (RBUS). As many as 50% of children with pyelonephritis have underlying VUR and up to 2% of this population have findings on RBUS that result in further evaluation and management.^5,13 Thus, RBUS is employed as a screening tool to identify those patients at risk for high-grade VUR or other anatomic anomalies. RBUS should only be completed during the first 2 days of therapy if the illness is unusually severe or if there is no improvement in clinical status.¹³ Otherwise, RBUS may delayed to the next most convenient time.

Radionuclide scanning (or renal cortical scintigraphy) using technetium-99 m DMSA was previously the test of choice to diagnose upper UTIs. DMSA is injected intravenously and uptake by the kidneys is measured several hours later. Areas of decreased uptake represent pyelonephritis or scarring. A negative DMSA scan, performed during the acute infection or months later, suggests that scarring in the future is unlikely.^5,21,22 However, while DMSA scintigraphy has a greater sensitivity for detecting acute pyelonephritis, it is not recommended routinely. This study rarely affects clinical management and may result in unnecessary cost and radiation exposure.¹³

Voiding cystourethrograms (VCUGs) are the diagnostic test of choice to evaluate for VUR. When mild, VUR is not associated with an increased incidence of UTI or morbidity and resolves spontaneously in most cases. Thus, while VUR is the most common abnormality of the urinary tract, VCUG is no longer recommended routinely in children between 2 months and 2 years of age who present with their first febrile UTI. Rather, current AAP recommendations suggest obtaining a VCUG only if RBUS reveals hydronephrosis, scarring, or other findings suggestive of high-grade VUR or obstructive uropathy.¹³ This recommendation has been challenged by the AAP Section on Urology secondary to concerns that moderate-to-severe VUR may be missed, resulting in recurrent infections and increased renal scarring.²³ Much of the controversy revolves around use of antibiotic prophylaxis in children with VUR and whether, if diagnosed by VCUG, any intervention is warranted. Based on a formal meta-analysis, the AAP subcommittee on UTI determined that antibiotic prophylaxis did not provide any statistically significant difference in recurrence rates of febrile UTIs/pyelonephritis in children with Grade IV VUR or less. Furthermore, there were too few children diagnosed with grade V VUR to provide conclusive results. However, other studies have shown a statistically significant reduction of recurrent UTIs in children who receive antibiotic prophylaxis and a nonsignificant increase in antibiotic-resistant UTIs.²⁴ Thus the evidence is still inconclusive. However, it should be noted that VCUG does carry the risk of radiation exposure and can be traumatizing to young children. The risk-to-benefit ratio must be carefully considered.

Current recommendations are to obtain an RBUS for any child with a febrile UTI (some recommend only <5 years) and boys of any age with a first UTI. Children with recurrent UTI or a first UTI associated with known urinary tract abnormalities, voiding dysfunction, hypertension, poor growth, or family history of renal disease are also candidates for an RBUS and a VCUG.^5,22 Children who do not respond promptly to therapy should undergo an RBUS to evaluate for the presence of a perirenal abscess or obstruction.⁵ Table 86-3 summarizes the types of diagnostic tests, their indications, and limitations.

Urolithiasis refers to stone formation in the bladder, ureter, or kidney. It is less common in children than it is in adults, but nevertheless has been reported in approximately 1 case per 7500 pediatric hospital admissions and its incidence has been on the rise in the last decade. ^25,28 Risk of renal stones is associated with a number of factors including, gender, geographic region, hydration status, diet, underlying disease, and socioeconomic status.^26–33 The incidence of stones is highest in the southeastern and western United States.²⁵ Urolithiasis is less common in Blacks but equally as common in girls as in boys, with a mean age of 9 years at presentation.^25,26,32

Pathophysiology

Causes of urinary tract stones can be divided into primary or metabolic causes, and secondary causes (Table 86-4).³¹ Primary causes comprise about 50% of cases and include hypercalciuria, cystinuria, hyperoxaluria, and hypocitraturia.^25,31,33 Hypercalciuria being by far the most common occurring in as much as 5% to 10% of the general population. ³⁴ Secondary causes are many and broadly include anatomic abnormalities of the genitourinary tract, such as VUR, various forms of obstruction of flow in the genitourinary tract, and postsurgical changes such as those related to bladder augmentation; infectious etiologies including organisms that contain urease, an enzyme that catalyzes urea (e.g., Staphylococcus, Proteus,Klebsiella, Serratia, and Pseudomonas); diet, such as high protein or ketogenic diets; underlying medical conditions including renal tubular acidosis, cystic fibrosis, hyperparathyroidism, prolonged immobilization, malignancies, and many others; and use of certain medications, such as indinavir, ceftriaxone, and prolonged corticosteroid therapy.^{25,31,35–37}

Most urinary calculi are calcium oxalate (40%–65%), followed in frequency by calcium phosphate (14%–30%), struvite (10%–20%), cystine (5%–10%), and uric acid (1%–4%). ^30,38,39

Signs and Symptoms

The classic signs of sudden onset of flank pain, nausea, vomiting, dysuria, and hematuria are not common in children. The younger the child, the more atypical the presentation, for example an infant may present with nonspecific symptoms, such as irritability, crying, signs of colic, or vomiting. Persaud et al. in a study of 110 cases of children with urolithiasis presenting to the ED, found 96% had abdominal or flank pain, 55% had nausea or vomiting, 15% had no hematuria and 13% presented with dysuria. Factors that predicted the presence of stones on CT included personal history of stones (OR 6.55; 95% CI 2.91–14.76), hematuria >2 RBCs per HPF (OR 3.10; 95% CI 1.45–6.66); history of nausea and vomiting (OR 2.39; 95% CI 1.28–4.47); and presence of flank pain (OR 2.23; 95% CI 1.17–4.25).⁴⁰ Interestingly, history of fever, dysuria, and costovertebral tenderness on physical examination were inversely associated with urolithiasis.⁴⁰

The emergency physician should solicit a history of previous urolithiasis, recurrent UTIs, frequent bouts of abdominal pain, a family history of stones, a history of microscopic or gross hematuria, or passage of stones or gravel in the urine. Patients are questioned about their diet, including intake of vitamins C and D, fluid and salt intake, consumption of soft drinks, especially those containing phosphoric acid, special diets (e.g., ketogenic diet), and use of herbal, holistic, or alternative medications. A complete list of medications should be obtained with and emphasis on those known to promote stone formation, such as diuretics, protease inhibitors, corticosteroids, antibiotics (e.g., ceftriaxone), and anticonvulsants. Children with a history of genitourinary tract abnormalities, frequent urinary infections, intestinal malabsorption such as inflammatory bowel disease or cystic fibrosis, and prolonged immobilization, such as after trauma, predispose a child to urolithiasis. Finally, other underlying medical conditions such as Wilson disease, hyperparathyroidism, Lesch–Nyhan syndrome, William syndrome, Dent disease, and malignancies (e.g., lymphoma and leukemia) have been associated with increased risk for stone formation. ^{25–27,31,39}

Perform a complete physical examination including evaluation of the blood pressure and growth parameters.

Diagnostic Evaluation

Obtain a urinalysis, urine Gram stain, urine culture, and renal function studies on all children with possible urinary tract stones. Urinalysis may reveal hematuria or be entirely normal. A complete blood cell count, renal function tests, electrolytes, calcium, phosphorous, magnesium, uric acid, total protein, and albumin may also be obtained.³¹

Once the diagnosis is suspected from history, physical examination findings, and laboratory analysis, obtain a CT scan of the abdomen without contrast. It is the diagnostic test of choice by the American College of Radiology for adults and children for patients with first-time presentations or in whom multiple alternative diagnoses are being considered.^41,42

Although 80% to 90% of stones are radiopaque, plain radiography has poor sensitivity and specificity so unhelpful in the evaluation of the child acutely in the ED, but may be used to track the progression of a radiopaque stone during follow-up visits.^31,39,40

Renal ultrasound has a high rate of detection (90%) of renal calculi, but a poor detection rate (38%) for ureteral calculi.³¹ Ultrasound may be useful in detecting hydronephrosis with pooled sensitivities of 85% to 90% and specificities of 90% to 100%. ⁴⁰ Thus, ultrasound may be useful in those patients who are pregnant, or for evaluating children with recurrent disease.^41–43

In the ED, patients are evaluated for signs of infection and given adequate hydration. Morphine sulfate with ketorolac has been found in adults to be superior to morphine sulfate alone for pain control in adult patients with renal colic.⁴⁴ Ketorolac as an analgesic has been shown to be safe for short-term use in infants and children in multiple settings requiring pain control.^45,46

Patients who have adequate pain control, renal function is normal, are able to drink fluids without vomiting, and have no sign of infection may be safely discharged home. Outpatient therapy should include encouragement of fluids and pain control. Stone passage depends on size, shape of stone, and location of the stone in genitourinary tract. Most stones in children <4 mm will pass spontaneous.^31,43,47 In addition, the adult literature supports the use of medical expulsion therapy (MET) with tamsulosin or terazosin, which are alpha-1 selective blockers to facilitate stone passage.^8,43,48 Mokhless et al.,⁴⁹ in a randomized study involving 61 children, with distal ureteral calculi <12 mm in size, demonstrated that the group receiving tamsulosin had a significantly higher passage rate (87.8% vs. 64.2%, p <0.001). Recurrences in children are high (24%–33%), thus consultation with a nephrologist and pediatric urologist for a metabolic evaluation, diet modification, and other possible therapy depending on the underlying etiology and success of medical management.^31,39,40,43

If medical therapy fails, other options for management include extracorporeal shock-wave lithotripsy (ESWL), ureteroscopy, percutaneous nephrostolithotomy, and open renal surgery.^31,50–52 Most stones in children can be managed with ESWL, considered the first-line interventional therapy, or with endoscopic techniques.^31,52 Overall, these techniques are safe but require sedation and anesthesia.

Patients with complete urinary obstruction, intractable pain, dehydration, a solitary kidney, renal insufficiency, or UTI should be admitted for hydration, parenteral pain medication, and antibiotic therapy as appropriate.³¹