Work

Urine NGAL adds to serum creatinine in predicting cefepime clearance in critically ill children at high risk of acute kidney injury

Year: 2026

Type: article

Abstract: • Adding urine neutrophil gelatinase-associated lipocalin, or uNGAL, to a serum creatinine-based cefepime population pharmacokinetic model improves prediction of cefepime clearance , identifying children at risk for altered drug exposure early in critical illness. • Elevated uNGAL (≥500 ng/mL) was associated with ∼35% lower cefepime clearance after accounting for creatinine-based estimated glomerular filtration rate. • Patients with a low (<500 ng/mL) uNGAL but elevated creatinine had higher-than-expected clearance than that based on creatinine alone , suggesting a functional, rather than structural, AKI phenotype. • Monte Carlo simulations suggested that patients with a low uNGAL would benefit from extended or continuous infusions to achieve adequate pharmacokinetic/pharmacodynamic target attainment. • Urine biomarker-guided dosing strategies could help optimize antibiotic therapy early in pediatric critical illness and warrant further study . Cefepime clearance (CL) depends on renal function, but serum creatinine (SCr) lags behind real-time changes in kidney function. Urinary neutrophil gelatinase–associated lipocalin (uNGAL) is a biomarker of real-time tubular injury, though its role in predicting cefepime pharmacokinetics (PK) is unclear. We conducted a prospective study in pediatric intensive care unit (PICU) patients at high risk for acute kidney injury who received cefepime within 48 hours of admission and had uNGAL measured. A validated population PK model incorporating SCr-estimated GFR (eGFR) was adapted to test the added predictiveness of uNGAL. Inter-occasion variability (IOV) assessed whether CL and central volume (V1) differed after 48 hours of PICU admission. Monte Carlo simulations (n=10,000) evaluated the probability of pharmacodynamic (PD) target attainment (PTA) for various cefepime regimens and PK/PD targets across weight groups (5–40 vs 40–100 kg), kidney function strata (eGFR 30–60, 60–90, 90–150 mL/min/1.73m²), and uNGAL thresholds (≥500 vs <500 ng/mL). Fifty patients (median age 11.5 years) were enrolled. PICU admission uNGAL ≥500 ng/mL was associated with ∼35% lower CL, independent of eGFR, with IOV at 4 hours post-PICU admission significant for CL and V1. Patients with low uNGAL had higher CL at a given eGFR with consequently lower PTA for a given dosing regimen, necessitating extended or continuous infusions to reach PK/PD targets. Integrating uNGAL improves prediction of cefepime CL beyond SCr alone. Patients with low uNGAL despite elevated SCr risked subtherapeutic exposure. Urine biomarker-guided dosing may help optimize PTA and warrants further study.

Source: International Journal of Antimicrobial Agents

DOI: 10.1016/j.ijantimicag.2026.107741