Urine Biomarkers of Acute Kidney Injury and Association with Brain MRI Abnormalities in Hypoxic-Ischemic Encephalopathy

Abstract

Abstract Objective: Determine whether urine biomarkers NGAL (neutrophil gelatinase-associated lipocalin), KIM-1 (kidney injury molecule 1) and IL-18 (interleukin 18) are associated with abnormal MRI findings in neonates with hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). Study Design: Secondary analysis of a multicenter, prospective study of neonates with HIE requiring TH. Urine biomarkers were obtained at 12 and 24 hours of life (HOL). Brain MRI was scored per NICHD criteria. Association between biomarkers and MRI stage was determined. Results: In 57 neonates with HIE, only IL-18 at 24 HOL was significantly increased in neonates with MRI Stage 2B or greater, compared to Stage 2A or less (mean 398.7 vs. 182.9 pg/mL, p=0.024.) A multivariate model including IL-18 at 24 HOL and 5-minute APGAR performed best, with an AUC of 0.84 (SE=0.07, p=0.02). Conclusions: Elevated urine IL-18 at 24 HOL was associated with more severe brain MRI abnormalities among neonates with HIE.