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Abstract: PO0190

Urine Biomarkers of AKI in Extremely Low Gestational Age Neonates: A Case-Control Study

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

  • Askenazi, David J., The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Halloran, Brian A., The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Schmicker, Robert, University of Washington School of Medicine, Seattle, Washington, United States
  • Heagerty, Patrick James, University of Washington School of Medicine, Seattle, Washington, United States
  • Juul, Sandra, University of Washington School of Medicine, Seattle, Washington, United States
  • Goldstein, Stuart, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Hingorani, Sangeeta R., Seattle Children's Hospital, Seattle, Washington, United States
  • Reagan, Meagan, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
Background

Urine biomarkers hold promise to diagnose and differentiate AKI. In premature neonates, biomarker evaluation must address normative gestational age (GA) differences.

Methods

We performed a case-control study from neonates enrolled in the Preterm Erythropoietin Neuroprotection Trial (PENUT) to evaluate differences in urine obtained in the first postnatal week between cases and controls. Twenty (N=20) neonates with severe AKI (Stage 2 or 3) were matched with 2 controls (N = 40) who did not have AKI, had the same GA week (rounded down to the nearest week), gender, and BW (+/- 50 g), without replacement. Biomarkers were analyzed on multi-analyte electro-chemiluminescent or single colorimetric ELISA kits. Biomarker were run in duplicates; the average concentration was converted to log10. Days were grouped into day 0-3, 4-6, 7-9, with day of birth was defined as day 0.
For each biomarker, the average pairwise difference between cases and controls was calculated. To account for multiple measurements, a linear mixed model framework was employed incorporating a random intercept for match, random effects across day, and a day case status interaction term. The predicted mean differences (95% CI) between cases and controls for each measurement time frame are compared and reported in the figures.

Results

Demographic characteristics were similar between those with and without AKI. The association with case status was modified by day (interaction p-values <0.05) for (Albumin, Clusterin, Creatinine, Cystatin C, epithelial growth factor (EGF), kidney injury marker-1 (KIM1), neutrophil gelatinase associated lipocalin (NGAL), FGF23, Ghrelin, IGFBP7, IL15, MCP1, TIMP2, VEGFA). Figures show a forest plot of the predicted mean differences (case minus control) at days 1 (0-3), 5 (4-6), and 9 (7-9) for each of 21 urine biomarkers. Urine albumin (day 1), EGF (day 1), creatinine (day 5 and 9), Cystatin C (Day 9), KIM-1 (day 9), IL-15 (day 9), and VEGFa (day 5) were significant differences between cases and controls.

Conclusion

Several urine biomarker concentrations differed in extremely low gestational age neonates with severe AKI vs. control. Further evaluation of these biomarkers is needed before clinical utility can be addressed.

Funding

  • Other NIH Support