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

Friday, April 28, 2023

5:15 PM – 7:15 PM ET

Poster Number: 170
Publication Number: 170.136

Megan J.. Turner, University of Colorado School of Medicine, Denver, CO, United States; Jennifer Rumpel, University of Arkansas for Medical Sciences College of Medicine, little rock, AR, United States; Beverly J. Spray, Arkansas Children's Research Institute, Little Rock, AR, United States; Nicholas Stence, University of Colorado School of Medicine, Aurora, CO, United States; Ilana Neuberger, Children's Hospital Colorado, Aurora, CO, United States; Valerie Y. Chock, Stanford University School of Medicine, Sunnyvale, CA, United States; Katja M. Gist, Children's Hospital Medical Center (Cincinnati), Cincinnati, OH, United States

Presenting Author(s)

Megan J. Turner, MD, MPH (she/her/hers)

Neonatologist, Assistant Professor of Pediatrics
University of Colorado School of Medicine
Denver, Colorado, United States

Background:

Acute kidney injury (AKI) is associated with worse outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) and can be predicted by urine biomarkers NGAL, KIM-1, and IL-18. The extent of brain injury after HIE is difficult to predict, though NICHD injury score of 2B or greater is associated with death or IQ < 70 at 6-7 years of age. We hypothesized that elevated NGAL, KIM-1, and/or IL-18 within the first 24 hours after birth would be associated with abnormal brain MRI findings.

Objective: Determine whether urine biomarkers NGAL, KIM-1 and IL-18 are associated with abnormal MRI findings in neonates with HIE who underwent therapeutic hypothermia (TH)

Design/Methods: Secondary analysis of a multicenter, prospective observational study of 57 neonates with HIE requiring TH based on Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) criteria was examined. Urine NGAL, KIM-1 and IL-18 were obtained at 12 and 24 hours of life (HOL). De-identified brain MRI obtained between DOL 4-7 were independently scored according to NICHD criteria by two pediatric neuroradiologists. Percent agreement, as determined by weighted kappa, was 97.8. Multivariate ANOVA was used to determine the relationship between mean biomarker levels and MRI stage, dichotomized as “Stage 2a or less” and “Stage 2b or greater.” Binary logistic regression was performed to determine the accuracy of any biomarker predicting MRI stage of 2b or greater using a threshold level of the urine biomarker(s).

Results: Of 57 neonates with HIE, 52.6% were male, mean gestational age was 38.8 weeks (SD=1.7), and average birth weight was 3393g (SD=570.40). NGAL, KIM-1 and IL-18 levels did not differentiate between MRI stage at 12 HOL (p >.05), nor did NGAL and KIM-1 levels differentiate between MRI stage at 24 HOL (p >.05). IL-18 levels at 24 HOL were significantly increased in neonates with an advanced MRI stage (M = 398.7; SD = 475.1) compared to those with stage 2a or less (M = 182.9; SD = 413.6, p = 0.024). Logistic regression analysis yielded an area under the curve (AUC) estimate of .73. IL-18 levels at 24 HOL varied greatly from 2.2 to 2000 pg/mL; precluding the determination of a clear cutoff value to predict advanced stage MRI findings.

Conclusion(s):

Elevated levels of urine IL-18 at 24 HOL were associated with brain MRI abnormalities stage 2b or greater among neonates with HIE. An AUC of 0.73 suggests a fair relationship between IL-18 and advanced MRI abnormalities, but variability in IL-18 levels yielded uncertain thresholds to predict advanced MRI stage.