Host and Bacterial Markers that Differ in Children with Cystitis and Pyelonephritis

Abstract

Objective: To determine whether treatment for urinary tract infections in children could be individualized using biomarkers for acute pyelonephritis.

Study design: We enrolled 61 children with febrile urinary tract infections, collected blood and urine samples, and performed a renal scan within 2 weeks of diagnosis to identify those with pyelonephritis. Renal scans were interpreted centrally by 2 experts. We measured inflammatory proteins in blood and urine using LUMINEX or an enzyme-linked immunosorbent assay. We evaluated serum RNA expression using RNA sequencing in a subset of children. Finally, for children with Escherichia coli isolated from urine cultures, we performed a polymerase chain reaction for 4 previously identified virulence genes.

Results: Urinary markers that best differentiated pyelonephritis from cystitis included chemokine (C-X-C motif) ligand (CXCL)1, CXCL9, CXCL12, C-C motif chemokine ligand 2, INF γ, and IL-15. Serum procalcitonin was the best serum marker for pyelonephritis. Genes in the interferon-γ pathway were upregulated in serum of children with pyelonephritis. The presence of E coli virulence genes did not correlate with pyelonephritis.

Conclusions: Immune response to pyelonephritis and cystitis differs quantitatively and qualitatively; this may be useful in differentiating these 2 conditions.

Keywords: UTI; calculator; diagnostic accuracy; prediction rule; risk.

Figure 1.

Flowsheet

Figure 2.

Heatmap showing relative expression. Green, red and black denote low, high, and median expression levels, respectively. Each row represents a gene and each column represent a patient. The black and red bars on top denote the pyelonephritis group and cystitis groups, respectively.