Febrile Urinary Tract Infections in Children: The Role of High Mobility Group Box-1

Background: Differentiating between febrile lower urinary tract infection (LUTI) and acute pyelonephritis (APN) is crucial for prompt clinical management. We investigated whether the high mobility group box-1 (HMGB1) could be a useful biomarker in differentiating between LUTI or APN. Methods: We enrolled seventy-four pediatric patients with suspected LUTI/APN, according to the positive or negative renal scintigraphy (DMSA) scan. If the first DMSA findings were abnormal, a second DMSA was performed after six months. Voiding cystourethrography ruled out vesicoureteral reflux (VUR). Results: Higher serum (s) HMGB1 levels characterized the APN group when compared to LUTI patients (13.3 (11.8-14.3) versus 5.9 (5.2-6.8) ng/mL, p: 0.02), whereas there were no differences according to urine (u) HMGB1 values. sHMGB1 correlated with C-reactive protein (CRP) levels (beta = 0.47; p: 0.02). Receiver operating characteristic curves identified the best diagnostic profile for detecting APN. sHMGB1 area under the curve was different from CRP (p: 0.01) and white blood cells (p: 0.003). After multivariate analyses, VUR (HR:4.81) and sHMGB1 (HR 1.16; p: 0.006) were independently associated with the risk of renal scarring development. Conclusions: sHMGB1 could represent a marker to differentiate APN from LUTI. Measurement of sHMGB1 could select children for early intervention or long-term follow-up.

Automated summary

This study found that high mobility group box-1 (HMGB1) could serve as a useful biomarker in differentiating between febrile lower urinary tract infection (LUTI) and acute pyelonephritis (APN). Serum HMGB1 levels were higher in APN patients compared to LUTI patients, while urine HMGB1 values showed no differences. Serum HMGB1 correlated with C-reactive protein levels, and its area under the curve was different from CRP and white blood cells in detecting APN. Serum HMGB1 and vesicoureteral reflux were independently associated with the risk of renal scarring development.