TY - JOUR
T1 - Gestational age, sex, and time affect urine biomarker concentrations in extremely low gestational age neonates
AU - on behalf of the PENUT Trial Consortium
AU - Askenazi, David J.
AU - Halloran, Brian A.
AU - Heagerty, Patrick J.
AU - Schmicker, Robert H.
AU - Brophy, Patrick
AU - Juul, Sandra E.
AU - Hingorani, Sangeeta
AU - Goldstein, Stuart L.
AU - Juul, Sandra E.
AU - Comstock, Bryan A.
AU - Wadhawan, Rajan
AU - Mayock, Dennis E.
AU - Courtney, Sherry E.
AU - Robinson, Tonya
AU - Ahmad, Kaashif A.
AU - Bendel-Stenzel, Ellen
AU - Baserga, Mariana
AU - LaGamma, Edmund F.
AU - Downey, L. Corbin
AU - Rao, Raghavendra
AU - Fahim, Nancy
AU - Lampland, Andrea
AU - Frantz, Ivan D.
AU - Khan, Janine Y.
AU - Weiss, Michael
AU - Gilmore, Maureen M.
AU - Ohls, Robin
AU - Srinivasan, Nishant
AU - Perez, Jorge E.
AU - McKay, Victor
AU - Vu, Phuong T.
AU - Heagerty, Patrick J.
N1 - Funding Information:
All authors declare no real or perceived conflicts of interest that could affect the study design, collection, analyses, and interpretation of data, writing of the report, or the decision to submit for publication. For full disclosure, we provide here an additional list of other authors’ commitments and funding sources that are not directly related to this study: D.J.A. is a consultant for Baxter, Nuwellis, Medtronic, Bioporto, AKI foundation, and SeaStar. He also receives external education and research funding not related to this project from Baxter, Nuwelis, and Medtronic. S.L. G. reports personal fees from and a position as a consultant to Nuwellis, Renibus, ExThera, Reata, and Medtronic Inc. S.L.G. receives grant funding from and serves as a consultant and on a Speaker’s Bureau for Baxter Healthcare, Inc. S.L.G. receives grant funding and serves as a consultant for BioPorto, Inc. S.L.G. serves on a Speaker’s Bureau for Fresenius Medical Corporation. S.E.J. receives grant funding from NINDS and NICHD for studies not related to this project. P.J.H. and R.H.S. receive grant funding from NHLBI and PCORI for studies not related to this project.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
PY - 2022/7
Y1 - 2022/7
N2 - Background: Our understanding of the normative concentrations of urine biomarkers in premature neonates is limited. Methods: We evaluated urine from 750 extremely low gestational age (GA) neonates without severe acute kidney injury (AKI) to determine how GA affects ten different urine biomarkers at birth and over the first 30 postnatal days. Then, we investigated if the urine biomarkers changed over time at 27, 30, and 34 weeks postmenstrual age (PMA). Next, we evaluated the impact of sex on urine biomarker concentrations at birth and over time. Finally, we evaluated if urine biomarkers were impacted by treatment with erythropoietin (Epo). Results: We found that all ten biomarker concentrations differ at birth by GA and that some urine biomarker concentrations increase, while others decrease over time. At 27 weeks PMA, 7/10 urine biomarkers differed by GA. By 30 weeks PMA, 5/10 differed, and by 34 weeks PMA, only osteopontin differed by GA. About half of the biomarker concentrations differed by sex, and 4/10 showed different rates of change over time between males vs. females. We found no differences in urine biomarkers by treatment group. Conclusions: The temporal patterns, GA, and sex differences need to be considered in urine AKI biomarker analyses. Impact: Urine biomarker concentrations differ by GA at birth.Some urine biomarkers increase, while others decrease, over the first 30 postnatal days.Most urine biomarkers differ by GA at 27 weeks PMA, but are similar by 34 weeks PMA.Some urine biomarkers vary by sex in premature neonates.Urine biomarkers did not differ between neonates randomized to placebo vs. Epo.
AB - Background: Our understanding of the normative concentrations of urine biomarkers in premature neonates is limited. Methods: We evaluated urine from 750 extremely low gestational age (GA) neonates without severe acute kidney injury (AKI) to determine how GA affects ten different urine biomarkers at birth and over the first 30 postnatal days. Then, we investigated if the urine biomarkers changed over time at 27, 30, and 34 weeks postmenstrual age (PMA). Next, we evaluated the impact of sex on urine biomarker concentrations at birth and over time. Finally, we evaluated if urine biomarkers were impacted by treatment with erythropoietin (Epo). Results: We found that all ten biomarker concentrations differ at birth by GA and that some urine biomarker concentrations increase, while others decrease over time. At 27 weeks PMA, 7/10 urine biomarkers differed by GA. By 30 weeks PMA, 5/10 differed, and by 34 weeks PMA, only osteopontin differed by GA. About half of the biomarker concentrations differed by sex, and 4/10 showed different rates of change over time between males vs. females. We found no differences in urine biomarkers by treatment group. Conclusions: The temporal patterns, GA, and sex differences need to be considered in urine AKI biomarker analyses. Impact: Urine biomarker concentrations differ by GA at birth.Some urine biomarkers increase, while others decrease, over the first 30 postnatal days.Most urine biomarkers differ by GA at 27 weeks PMA, but are similar by 34 weeks PMA.Some urine biomarkers vary by sex in premature neonates.Urine biomarkers did not differ between neonates randomized to placebo vs. Epo.
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U2 - 10.1038/s41390-021-01814-x
DO - 10.1038/s41390-021-01814-x
M3 - Article
C2 - 34845352
AN - SCOPUS:85120179309
SN - 0031-3998
VL - 92
SP - 151
EP - 167
JO - Pediatric Research
JF - Pediatric Research
IS - 1
ER -