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Preterm neonatal urinary renal developmental and acute kidney injury metabolomic profiling: an exploratory study

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Abstract

Background

Acute kidney injury (AKI) staging has been developed in the adult and pediatric populations, but these do not yet exist for the neonatal population. Metabolomics was utilized to uncover biomarkers of normal and AKI-associated renal function in preterm infants. The study comprised 20 preterm infants with an AKI diagnosis who were matched by gestational age and gender to 20 infants without an AKI diagnosis.

Methods

Urine samples from pre-term newborn infants collected on day 2 of life were analyzed using broad-spectrum nuclear magnetic resonance (NMR) metabolomics. Multivariate analysis methods were used to identify metabolite profiles that differentiated AKI and no AKI, and to identify a metabolomics profile correlating with gestational age in infants with and without AKI.

Results

There was a clear distinction between the AKI and no-AKI profiles. Two previously identified biomarkers of AKI, hippurate and homovanillate, differentiated AKI from no-AKI profiles. Pathway analysis revealed similarities to cholinergic neurons, prenatal nicotine exposure on pancreatic β cells, and amitraz-induced inhibition of insulin secretion. Additionally, a pH difference was noted. Both pH and the metabolites were found to be associated with AKI; however, only the metabotype was a significant predictor of AKI. Pathways for the no-AKI group that correlated uniquely with gestational age included aminoacyl-t-RNA biosynthesis, whereas pathways in the AKI group yielded potential metabolite changes in pyruvate metabolism.

Conclusions

Metabolomics was able to differentiate the urinary profiles of neonates with and without an AKI diagnosis and metabolic developmental profiles correlated with gestational age. Further studies in larger cohorts are needed to validate these results.

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Acknowledgements

We thank Zachery Acuff and Dr Jason Burgess for their contributions to this study. This project was performed as a collaboration through the NIH Eastern Regional Comprehensive Metabolomics Resource Core (RTI RCMRC), a NIH Common Fund award through NIDDK, Project Number 1U24DK097193-01 (Sumner), the Norman Siegel Career Development Award from the American Society of Nephrology/The UAB Center for Clinical and Translational Science UL1 TR000165 (Askenazi), and the University of Iowa Institute for Clinical and Translational Science UL1RR024979 (Brophy).

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Authors and Affiliations

  1. RTI International, 3040 E. Cornwallis Road, Research Triangle Park, Triangle, NC, 27709, USA

    Kelly Mercier, Susan McRitchie, Wimal Pathmasiri, Andrew Novokhatny & Susan Sumner

  2. University of Alabama Children’s Hospital, Birmingham, AL, USA

    Rajesh Koralkar & David Askenazi

  3. University of Iowa Children’s Hospital, 1269A-CBRB Newton Road, Iowa City, IA, 52242, USA

    Patrick D. Brophy

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  1. Kelly Mercier
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  2. Susan McRitchie
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  3. Wimal Pathmasiri
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  4. Andrew Novokhatny
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  5. Rajesh Koralkar
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  6. David Askenazi
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  7. Patrick D. Brophy
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  8. Susan Sumner
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Corresponding authors

Correspondence to Patrick D. Brophy or Susan Sumner.

Ethics declarations

This study was approved by the University of Alabama at Birmingham (UAB) Institutional Review Board; informed parental consent was obtained for all infants. The clinical and research activities being reported are consistent with the principles of the Declaration of Helsinki.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Patrick D. Brophy and Susan Sumner are co-senior authors

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Mercier, K., McRitchie, S., Pathmasiri, W. et al. Preterm neonatal urinary renal developmental and acute kidney injury metabolomic profiling: an exploratory study. Pediatr Nephrol 32, 151–161 (2017). https://doi.org/10.1007/s00467-016-3439-9

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  • DOI: https://doi.org/10.1007/s00467-016-3439-9

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