Urinary NT-proBNP as a noninvasive biomarker for pediatric septic shock: a comparative study with serum levels

The 2024 Phoenix Sepsis Score (PSS) may not fully capture subclinical cardiovascular stress in pediatric sepsis. N-terminal pro-B-type natriuretic peptide (NT-proBNP), released under haemodynamic strain, is measurable in urine and serum and has been associated with cardiovascular dysfunction. This study aimed to compare urinary and serum NT-proBNP levels in pediatric sepsis and septic shock, evaluate their ability to differentiate these conditions, and examine their correlations with PSS.

Participants aged 1 month-18 years with sepsis or septic shock according to PSS were included in this prospective cross-sectional analytical study at a tertiary hospital in Bandung, Indonesia. Urinary and serum NT-proBNP concentrations were measured within 48 h of diagnosis. Patients with preexisting heart, kidney, or urological problems were excluded. Main analyses included Mann-Whitney U, ROC curves, and Spearman correlations. To evaluate statistical stability, 1,000 bias-corrected and accelerated (BCa) bootstrap iterations, fragility index (FI) analysis, and time-adjusted sensitivity analyses were added.

Final analyses comprised 52 children (26 sepsis, 26 septic shock). Median urinary NT-proBNP levels were higher in septic shock than in sepsis (8,065 vs. 210 pg/mL; p = 0.003), as were serum NT-proBNP levels (1,655 vs. 200 pg/mL; p = 0.005). Urinary NT-proBNP had an AUC of 0.743 (95% BCa CI 0.584-0.867) for septic shock (cut-off > 9,550 pg/mL, specificity 100%, sensitivity 42.3%, FI = 4), whereas serum NT-proBNP showed an AUC of 0.726 (95% BCa CI 0.573-0.852; cut-off > 1,640 pg/mL, specificity 92.3%, sensitivity 50.0%, FI = 3). Sensitivity analyses confirmed performance stability when restricting collection to ≤ 6 h. Urinary NT-proBNP correlated weakly with PSS (r = 0.261; p = 0.031), while serum NT-proBNP did not (r = 0.221; p = 0.058).

Urinary NT-proBNP demonstrated moderate discriminatory ability and high specificity for pediatric septic shock, comparable to serum NT-proBNP, although its correlation with PSS was modest. It may have potential value as an adjunctive rule-in biomarker for cardiovascular stress in pediatric sepsis, but not as a screening tool or replacement for clinical assessment. Further studies are needed to determine its broader clinical utility in pediatric sepsis.