Polymorphonuclear Elastase as a Diagnostic Marker of Acute Pyelonephritis in Children
Authors: Fretzayas Andrew , Moustaki Maria , Gourgiotis Dimitrios , Bossios Apostolos , Koukoutsakis Petros , Stavrinadis Christodoulos 
Published: August 2004

Objective.
Experimental evidence suggests that neutrophils and their metabolites play an important role in the pathogenesis of pyelonephritis. The aim of this study was to investigate the diagnostic value of polymorphonuclear elastase-a1-antitrypsin complex (E-a1-Pi) for the detection of acute pyelonephritis in children.

Methods.
Eighty-three patients, 29 boys and 54 girls, 25 days to 14 years of age, with first-time symptomatic urinary tract infection were prospectively studied. Fifty-seven healthy children served as controls. Dimercaptosuccinic acid (DMSA) scan and voiding cystourethrography were performed in all patients. Plasma and urinary E-a1-Pi, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil count, urinary N-acetyl-β-glucosaminidase (NAG), N-acetyl-β-glucosaminidase b (NAG b), and creatinine levels were measured in all patients on admission and 3 days after the introduction of antibiotics. The same markers were also measured in the control subjects.

Results.
Planar DMSA scintigraphy demonstrated changes of acute pyelonephritis in 30 of 83 children (group A). It was normal in the remaining 53 children (group B). The sex and age distributions were not significantly different between the 2 groups, as well as between the patients and the control subjects (group C). Nineteen of the 53 children with a normal DMSA had body temperature ≥38°C, whereas all but 4 children with abnormal DMSA had temperature ≥38°C. Therefore, the temperature was significantly different between these 2 groups. The sensitivity and specificity of fever (≥38°C) as an indicator of renal involvement based on isotopic findings were 86% and 64%, respectively. Given the significant number of the febrile children with normal DMSA scintiscans, group B was subdivided into B1 with 19 febrile children (14 boys and 5 girls) and B2 with 34 children whose body temperature was below 38°C (8 boys and 26 girls). The sex and age distribution was significantly different between groups B1 and B2. The mean age of group B1 was .78 years (range: 28 days to 9 years; median: .25 years; standard deviation: 2.1). All but 1 child in this group were younger than 1 year of age. In contrast, in group B2, there were only 4 infants, the remaining 30 children were older than 2.5 years (mean age: 6 years; median: 7 years; standard deviation: 3.5; range: 34 days to 12 years). The mean duration of fever before hospital admission was 2.8 days for group A and 1.8 days for group B1. This difference was not statistically significant. Similarly, body temperature was not significantly different between these 2 groups. The distribution of plasma E-a1-Pi values was normal in the control subjects. The sensitivity and specificity of plasma E-a1-Pi, as an indicator of renal involvement, were 96% and 50%, respectively, taking the 95th percentile of the reference range as a cutoff value. However, considering as a cutoff value the level of 72 μg/dL (95th percentile of group B2), its sensitivity and specificity were 74% and 86%, respectively. Plasma E-a1-Pi levels were significantly elevated in group A compared with group B and in both groups, the plasma E-a1-Pi values were significantly higher than in the control subjects. A significant difference also was noticed between group A and each of the subgroups B1 and B2 and also between the subgroups themselves. Plasma E-a1-Pi concentrations correlated significantly with neutrophil count in groups A (r = .3), B (r = .4), and B2 (r= .46), but the correlation was not significant in group B1. ESR levels showed, among the different groups, similar differences with those of E-a1-Pi values. Unlike E-a1-Pi, CRP levels were comparable between groups A and B1, which both consisted of febrile children. Neutrophil count was not significantly different between subgroups B1and B2. Considering 20 mg/dL as a cutoff level for CRP, its sensitivity and specificity for identifying the urinary tract infection site were 69% and 57%, respectively. The sensitivity and specificity of ESR, using 30 mm/hour as a cutoff value, were 90% and 59%, respectively. The comparison of febrile infants with a normal DMSA scan (all but 1 child of group B1) with those with an abnormal one (a subpopulation of group A) showed significant difference of plasma E-a1-Pi and ESR but not of CRP and neutrophils. Urinary E-a1-Pi, as well as NAG and NAG b/creatinine values, showed no significant difference between groups A and B. NAG and NAG b levels were significantly higher in group B1compared with group B2 but they were similar with those of group A. Reflux was noticed in 16/83 children (19%), 9/30 children with an abnormal DMSA (30%) and 7/53 with a normal DMSA scan (13%); this difference was not statistically significant. The sensitivity and specificity of reflux, as an indicator for renal lesions on the DMSA scan, were 30% and 86%, respectively. The follow-up investigation on the third day revealed that plasma E-a1-Pi levels, as well as CRP, were significantly lower compared with their levels on admission within each group. Despite the fact that ESR levels were lower on the third day, the difference was not significant.

Conclusions.
Plasma E-a1-Pi is a sensitive but not a specific marker for the detection of acute pyelonephritis. Urinary E-a1-Pi levels cannot be used for this purpose.