International journal of antimicrobial agents · 2026
Urine NGAL adds to serum creatinine in predicting cefepime clearance in critically ill children at high risk of acute kidney injury.
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Hambrick Horace Rhodes, Junior Ronaldo Morales, Curry Calise, Collins Michaela, Johnson Luana, Mizuno Tomoyuki, Krallman Kelli A, Goldstein Stuart L, Tang Girdwood Sonya
Аннотация
INTRODUCTION: 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.
METHODS: We conducted a prospective study in paediatric intensive care unit (PICU) patients at high risk for acute kidney injury who received cefepime within 48 h 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 h 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).
RESULTS: Fifty patients (median age 11.5 y) were enrolled. PICU admission uNGAL ≥500 ng/mL was associated with ∼35% lower CL, independent of eGFR, with IOV at 4 h 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.
CONCLUSIONS: Integrating uNGAL improves the prediction of cefepime CL beyond SCr alone. Patients with low uNGAL despite elevated SCr risked subtherapeutic exposure. Urine biomarker-guided dosing may help optimise PTA and warrants further study.
METHODS: We conducted a prospective study in paediatric intensive care unit (PICU) patients at high risk for acute kidney injury who received cefepime within 48 h 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 h 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).
RESULTS: Fifty patients (median age 11.5 y) were enrolled. PICU admission uNGAL ≥500 ng/mL was associated with ∼35% lower CL, independent of eGFR, with IOV at 4 h 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.
CONCLUSIONS: Integrating uNGAL improves the prediction of cefepime CL beyond SCr alone. Patients with low uNGAL despite elevated SCr risked subtherapeutic exposure. Urine biomarker-guided dosing may help optimise PTA and warrants further study.