Urine Biomarkers for the Assessment of Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Receiving Therapeutic Hypothermia.

OBJECTIVE To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN We performed a multicenter prospective observational study of 64 neonates. Urine was obtained at 12, 24, 48, and 72 hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin 18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), insulin like growth factor binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO AKI criteria. RESULTS AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use (median [IQR], 2[0-5] days vs. 0 [0-2] days; P = .026). Mortality was greater in neonates with AKI (25% vs 2%; p=0.012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs only yielded a fair prediction. KIM-1 had the best predictive performance across time points with an AUC (SE) of 0.79 (0.11) at 48 HOL. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48 HOL. CONCLUSIONS Urine NGAL, KIM-1, and IL-18 were elevated in neonates with HIE receiving TH who developed AKI. However, wide variability and unclear cut off levels make their clinical utility unclear.