Procalcitonin, C-reactive protein, and erythrocyte sedimentation rate for the diagnosis of acute pyelonephritis in children

In some children with urinary tract infection (UTI), the infection is localized to the bladder (lower urinary tract). In others, bacteria ascend from the bladder to the kidney (upper urinary tract). Only children with upper urinary tract involvement are at risk for developing permanent kidney damage. If non-invasive biomarkers could accurately differentiate children with lower urinary tract disease from children with upper urinary tract disease, treatment and follow-up could potentially be individualized. Accordingly, we examined the usefulness of three widely available blood tests (procalcitonin, C-reactive protein, erythrocyte sedimentation rate) in differentiating upper from lower urinary tract disease. We found 24 relevant studies of which 17 provided data for our primary outcome. Six studies (434 children) provided data for the procalcitonin test; 13 studies (1638 children) provided data for the C-reactive protein test, and six studies (1737 children) provided data for the erythrocyte sedimentation rate test. We found all three tests to be sensitive (summary sensitivity values ranged from 86% to 95%), but not very specific (summary specificity values ranged from 38% to 71%). None of the tests were accurate enough to allow clinicians to confidently differentiate upper from lower urinary tract disease.

Authors' conclusions: 

The ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis. A low CRP value (< 20 mg/L) appears to be somewhat useful in ruling out pyelonephritis (decreasing the probability of pyelonephritis to < 20%), but unexplained heterogeneity in the data prevents us from making recommendations at this time. The procalcitonin test seems better suited for ruling in pyelonephritis, but the limited number of studies and the marked heterogeneity between studies prevents us from reaching definitive conclusions. Thus, at present, we do not find any compelling evidence to recommend the routine use of any of these tests in clinical practice.

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Background: 

In children with urinary tract infection (UTI), only those with pyelonephritis (and not cystitis) are at risk for developing long-term renal sequelae. If non-invasive biomarkers could accurately differentiate children with cystitis from children with pyelonephritis, treatment and follow-up could potentially be individualized.

Objectives: 

The objectives of this review were to 1) 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; 2) assess the influence of patient and study characteristics on the diagnostic accuracy of these tests, and 3) compare the performance of the three tests to each other.

Search strategy: 

We searched MEDLINE, EMBASE, DARE, Web of Science, and BIOSIS Previews for this review. The reference lists of all included articles and relevant systematic reviews were searched to identify additional studies not found through the electronic search.

Selection criteria: 

We only considered published studies that evaluated the results of an index test (procalcitonin, CRP, ESR) against the results of an acute-phase DMSA scan (conducted within 30 days of the UTI) in children aged 0 to 18 years with a culture-confirmed episode of UTI. The following cutoff values were used for the primary analysis: 0.5 ng/mL for procalcitonin, 20 mg/L for CRP and 30 mm/h for ESR.

Data collection and analysis: 

Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate pooled random-effects pooled sensitivity and specificity values.

Main results: 

A total of 24 studies met our inclusion criteria. Seventeen studies provided data for the primary analysis: six studies (434 children) included data on procalcitonin, 13 studies (1638 children) included data on CRP, and six studies (1737 children) included data on ESR (some studies had data on more than one test). The summary sensitivity estimates (95% CI) for the procalcitonin, CRP, ESR tests at the aforementioned cutoffs were 0.86 (0.72 to 0.93), 0.94 (0.85 to 0.97), and 0.87 (0.77 to 0.93), respectively. The summary specificity values for procalcitonin, CRP, and ESR tests at these cutoffs were 0.74 (0.55 to 0.87), 0.39 (0.23 to 0.58), and 0.48 (0.33 to 0.64), respectively.

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