Pediatric Pyelonephritis Workup

It is prudent to order urinalysis (and urine culture in those with abnormal findings) in all febrile boys younger than 6 months and febrile girls younger than 24 months with fever lasting more than 48 hours. Female adolescents who present with symptoms of UTI, pyelonephritis, and/or vaginitis and who are sexually active must be evaluated for pregnancy and sexually transmitted diseases.

An increased blood urea nitrogen (BUN) and/or creatinine level should raise the suspicion for hydronephrosis or renal parenchymal disease.

Urine must be collected with proper technique to be useful for diagnosing cystitis or acute pyelonephritis. Suprapubic bladder aspiration should be performed in uncircumcised male patients in whom the urethral meatus is not visible, as well as in infants with periurethral irritation.

Bladder catheterization is the appropriate technique for obtaining a urine sample in most infants and young children. In neonates, suprapubic bladder aspiration may be used. A clean-catch, midstream urine sample may be obtained in children who can cooperate and void on request.

A specimen collected by using sterile bag may be used for urinalysis but not for urine culture. A urine specimen that is positive for nitrite, leukocyte esterase, or blood may indicate UTI. Microscopic examination of an unspun sample that contains more than 10 white blood cells (WBCs) per high-powered field or any bacteria is highly predictive of a positive urine culture. Red blood cell (RBC) or WBC casts suggest underlying renal parenchymal disease. Epithelial cells suggest skin contamination. A normal result from urinalysis does not exclude pyelonephritis. ^[10]

Urine cultures must be obtained in all children with suspected pyelonephritis. Treatment should not be commenced on the basis of urinalysis results, and normal urinalysis findings do not exclude an infection. Acute pyelonephritis may be present even if urine cultures demonstrate no growth.

A clean-catch urine specimen with more than 100,000 colony-forming units (CFUs) of a single organism is considered diagnostic of a UTI. Organisms, such as Lactobacillus, Staphylococcus, or Corynebacterium species, may not be clinically relevant.

Cultures showing more than 100,000 CFUs of a single organism obtained by means of transurethral catheterization are 95% sensitive and 99% specific for UTI. Specimens growing 10⁴ CFUs may be consistent with infection, but the test should be repeated if infection is not likely and if treatment has not yet commenced.

Cultures from bagged urine specimens are useful only if no growth is observed. Bagged urine specimens result in a false-positive rate of 85%. Before treatment is started on the basis of results from a bagged-specimen test, a catheterized or suprapubic specimen should be obtained.

Structural abnormalities of the urinary tract may be associated with infections secondary to multiple organisms or unusual gram-negative bacteria, such as Pseudomonas aeruginosa.

Lertdumrongluk et al investigated whether urine heparin binding protein (UHBP), a cytokine released from activated neutrophils, was a useful diagnostic tool for acute pyelonephritis (APN) and concluded that UHBP is a valid adjunctive diagnostic tool for aiding clinicians in making rapid treatment decisions for APN. ^[11]

Some patients may have electrolyte abnormalities, which may be secondary to vomiting or diarrhea.

Secondary pseudohypoaldosteronism may develop, with impaired renal tubular function, in infants with pyelonephritis. Mild hyponatremia and hyperkalemia may be present. Infants with underlying urinary-tract anomalies have an increased risk of this electrolyte imbalance, which resolves when the infection is treated.

An elevated WBC count is nonspecific and does not help in distinguishing lower UTI from upper UTI. In the presence of a febrile UTI, however, an erythrocyte sedimentation rate (ESR) of more than 30 mm/h is highly predictive of acute pyelonephritis.

C-reactive protein (CRP) levels are correlated with parenchymal defects on DMSA scanning. Elevated CRP concentrations are sensitive, but nonspecific, markers of renal parenchymal involvement in the febrile infant and child with UTI. CRP values may be used to distinguish bladder colonization from acute pyelonephritis in a febrile child with bacteriuria and a neurogenic bladder.

Procalcitonin is an acute inflammatory marker with a sensitivity of 70-95% and a specificity that approaches 90% for renal involvement in infants and children with febrile UTI. Although less sensitive than CRP, procalcitonin is more specific for the diagnosis of acute pyelonephritis. Procalcitonin values are better correlated with long-term renal scarring than is CRP. ^{[12, 13]}

Procalcitonin levels near 0.5 ng/mL may not consistently correlate with acute pyelonephritis. As procalcitonin levels increase, the severity of renal lesions on DMSA increases. Higher levels of procalcitonin predict VUR in infants and children at the onset of pyelonephritis. ^[14]

Serum and urinary IL-6 and IL-8 are correlated with renal involvement in infants and children with UTI with high sensitivity (81-88%) and acceptable specificity (78-83%). These markers are not reliable in neonates with suspected acute pyelonephritis.

A Cochrane review aimed to determine whether procalcitonin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) can replace the acute DMSA scan in the diagnostic evaluation of children with UTI. The review found that the ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis. The review also reported that the procalcitonin test seems better suited for ruling in pyelonephritis, however, the study could not find any compelling evidence to recommend the routine use of any of these tests in clinical practice. ^[15]

A study reviewed 138 children with pediatric UTIs to compare the diagnostic accuracy of plasma neutrophil gelatinase-associated lipocalin (NGAL) with procalcitonin, C-reactive protein, and white blood cells for predicting acute pyelonephritis. The study reported that at the best cutoff values of all the biomarkers examined for diagnosing acute pyelonephritis, plasma NGAL level had the highest sensitivity (86%), specificity (85 %), positive predictive value (81%), and negative predictive value (89%). The study also found that 117 ng/ml was the optimal NGAL cutoff value. ^[16]

A study by Lee et al that retrospectively analyzed the data of 177 infants with febrile UTI reported that higher D-dimer levels can also be used as an inflammatory marker for acute pyelonephritis. ^[17]

Radiographic studies are generally not indicated to diagnose acute pyelonephritis. Studies may be indicated, however, if the child's condition does not respond to treatment as expected and if colonization must be distinguished from infection in the patient with chronic bacteriuria.

Guidelines from the American Academy of Pediatrics recommend imaging after first febrile UTIs in infants and young children to identify abnormalities that may predispose them to recurrent infection or renal scarring. ^[18]

In children who have not had ultrasonography performed in the prenatal period, this study may be useful to exclude congenital malformations but is otherwise not helpful in the evaluation of acute pyelonephritis. Renal ultrasonography is useful for determining the size and shape of the kidneys but is generally poor for visualizing nondilated ureters. In addition, it does not provide information regarding renal function.

Renal ultrasonography has low sensitivity (50%) in detecting acute pyelonephritis, although focal abnormalities on ultrasonography, combined with a CRP level of more than 70 mg/L, may be predictive of renal scarring.

Findings on power Doppler ultrasonography have been correlated with DMSA findings of acute pyelonephritis. Renal ultrasonography is useful in the diagnosis of urolithiasis, hydronephrosis, hydroureter, ureteroceles, and bladder distention. ^[19]

VCUG

Voiding cystourethrography (VCUG) is useful for visualizing the urethral and bladder anatomy and for the detecting VUR. Following a second febrile UTI, VCUG may be performed after 3-4 days of therapy to ensure that bladder irritability has resolved and that the urine is sterilized. The voiding phase is needed to evaluate for VUR and posterior urethral valves.

Consistent with new recommendations, VCUG is no longer required as a mandatory part of the evaluation of children with their first febrile urinary tract infection, ^[20] although it may be of benefit for infants with abnormal 6-month follow-up DMSA scans. ^[21]

Nuclear cystography

This study is good for evaluating the bladder and detecting VUR. However, it does not permit adequate evaluation of the urethra and is therefore not used for an initial evaluation of the urologic anatomy.

Cystography has only about 1% of the radiation dose of fluoroscopic study. Cystography may be used for serial follow-up studies.

Nuclear cortical scanning depicts tubular damage and scarring. It provides information regarding the general size of the kidneys; however, it does not provide detailed information regarding the collecting system. DMSA scanning is not necessary to evaluate or follow up most episodes of acute pyelonephritis, although DMSA has a sensitivity of more than 90% in detecting changes that are suggestive of acute pyelonephritis. Radiation exposure to the patient undergoing this procedure is low.

This study most frequently involves the use of technetium-99m (^99m Tc) DMSA to depict renal cortical scarring. The volume of the initial defect is useful in predicting the development of renal scars.

Follow-up DMSA scans performed more than 6 months after acute pyelonephritis resolves are useful to detect permanent renal scarring. Studies performed less than 6 months after acute pyelonephritis may reveal residua of the original infection rather than permanent scars.

DMSA scans can help in determining the cause of fever in children with chronic bacteriuria, such as patients with spinal-cord injury and those who undergo clean intermittent catheterization.

CT scanning

Enhanced computed tomography (CT) scanning may be useful in distinguishing acute pyelonephritis from other causes of fever. However, increased radiation exposure makes CT scanning a less favorable study in children, especially because ultrasonography is generally adequate in defining the anatomic structure. [#WorkupProcedures]

MRI

Gadolinium-enhanced magnetic resonance imaging (MRI) scans are correlated with DMSA scans in detecting renal parenchymal defects and are effective in distinguishing acute inflammation from scars. MRI is superior to nuclear scintigraphy in distinguishing acute inflammation from chronic scars. MR cystography may be useful in evaluating VUR. Sedation is generally required in MRI. ^{[22, 23]}