Impact of gestational age, sex, and postnatal age on urine biomarkers in premature neonates
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Urine proteins may help in understanding physiology and diagnosing disease in premature infants. Determining how urine proteins vary by degree of prematurity, sex, and postnatal day is warranted.
We performed a prospective cohort study to assess the independent correlation of 14 urine biomarkers (measured on postnatal days 1–4) with gestational age (GA), sex, and postnatal age in 81 premature infants (mean, 1017 g) without acute kidney injury using a random-effects mixed model.
Neutrophil gelatinase-associated lipocalin (NGAL) and vascular endothelial growth factor (VEGF) showed significant associations for sex, GA, and postnatal age. Cystatin C, osteopontin (OPN), and trefoil factor 3 (TFF3) were associated with postnatal age and GA, but not sex. Epithelial growth factor (EGF) and uromodulin were associated with GA only. Clusterin was associated with postnatal age and sex. Albumin was associated with sex only. Beta-2-microglbulin (B2M), osteoactivin, kidney injury molecule −1 (KIM-1), and alpha glutathione S-transferase (αGST) were associated with postnatal age only.
Postnatal age affects B2M, cystatin C, NGAL, OPN, clusterin, Kim-1, osteoactivin, TFF3, VEGF, αGST. GA affects cystatin C, EGF, NGAL, OPN, UMOD, TFF3, and VEGF. Sex affects albumin, NGAL, and clusterin. Interpretation of urine biomarkers will need to account for these associations.
KeywordsAcute kidney injury Acute renal failure Infant Reference Baseline NGAL KIM-1 Cystatin C
Statement of financial support
Research reported in this publication was supported by the Norman Siegel Career Development Award from the American Society of Nephrology and the UAB-UCSD O'Brien Center and Grant NIH P30-DK079337. Dr. Askenazi receives funding from the NIH (R01 DK13608-01) and the Pediatric and Infant Center for Acute Nephrology (PICAN) which is sponsored by Children’s of Alabama and the University of Alabama at Birmingham’s School of Medicine, Department of Pediatrics and Center for Clinical and Translational Science (CCTS) under award number UL1TR00165. Dr. Ambalavanan receives funding from NIH (grant # U01 HL122626; R01 HD067126; R01 HD066982; U10 HD34216). Dr. Griffin receives funding from UAB CCTS, and PICAN.
Conflicts of interest
Dr. Askenazi is speaker for The AKI Foundation.
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