Time Course of Kidney Injury Biomarkers in Children With Septic Shock: Nested Cohort Study Within the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis Trial.

Summary

In 478 children with septic shock, kidney injury biomarkers tracked AKI severity early, but only cystatin C remained elevated near discharge. Elevated urine NGAL identified subclinical AKI with fewer hospital-free days even when creatinine-based AKI was absent/mild. Receiving >100 mL/kg fluids in 48 hours doubled the odds of persistently elevated urine NGAL.

Key Findings

• All measured kidney injury biomarkers were higher with KDIGO stage 2/3 vs. no/stage 1 AKI at presentation and days 2–3.
• Only plasma cystatin C remained elevated prior to discharge/death (T3).
• Among children without/mild AKI at presentation, urine NGAL ≥150 ng/mL identified subclinical AKI and fewer hospital-free days.
• Fluid >100 mL/kg in 48 hours was associated with persistently elevated urine NGAL (IPTW-adjusted OR 2.7; 95% CI 1.1–6.2).

Clinical Implications

Consider integrating urine NGAL and cystatin C to detect subclinical AKI and guide fluid stewardship. Avoid exceeding >100 mL/kg within 48 hours when possible, pending RCT validation, and monitor kidney biomarkers for early injury.

Limitations

• Non-prespecified biomarker substudy; potential selection bias across three centers.
• No long-term kidney outcomes; creatinine-based AKI definition may miss tubular injury.

Future Directions

Randomized trials of biomarker-guided fluid strategies; validation of urine NGAL thresholds; integration with EHR alerts to prevent fluid-associated kidney injury.