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Urinary metabolomics to develop predictors for pediatric acute kidney injury

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Abstract

Background

Acute kidney injury (AKI) is characterized by an abrupt decline in glomerular filtration rate (GFR). We sought to identify separate early urinary metabolomic signatures at AKI onset (with-AKI) and prior to onset of functional impairment (pre-AKI).

Methods

Pre-AKI (n=15), AKI (n=22), and respective controls (n=30) from two prospective PICU cohort studies provided urine samples which were analyzed by GC-MS and DI-MS mass spectrometry (193 metabolites). The cohort (n=58) was 8.7±6.4 years old and 66% male. AKI patients had longer PICU stays, higher PRISM scores, vasopressors requirement, and respiratory diagnosis and less commonly had trauma or post-operative diagnosis. Urine was collected within 2–3 days after admission and daily until day 5 or 14.

Results

The metabolite classifiers for pre-AKI samples (1.5±1.1 days prior to AKI onset) had a cross-validated area under receiver operator curve (AUC)=0.93 (95%CI 0.85–1.0); with-AKI samples had an AUC=0.94 (95%CI 0.87–1.0). A parsimonious pre-AKI classifier with 13 metabolites was similarly robust (AUC=0.96, 95%CI 0.89–1.0). Both classifiers were similar and showed modest correlation of high-ranking metabolites (tau=0.47, p<0.001).

Conclusions

This exploratory study demonstrates the potential of a urine metabolite classifier to detect AKI-risk in pediatric populations earlier than the current standard of diagnosis with the need for external validation.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information with inner reference to ESM for GA

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Data availability

Patient level data is not publicly available. Primary data is available upon request from the corresponding author.

Code availability

Code for analysis in R is available, upon request from the corresponding author.

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Acknowledgements

We are grateful to the patients and parents who agreed to participate in the two primary studies on acute kidney injury.

Funding

This work was funded by an establishment grant by the BC Children’s Hospital Foundation. The primary research was funded by McGill University Health Centre Research Institute, the Kidney Research Scientist Core Education, National Training Program and the Fonds de Recherches en Santé du Quebec, a research salary award from the Fonds de Recherches du Quebec-Sante, and grants from the National Institutes of Health (NIH, P50DK096418).

Author information

Authors and Affiliations

  1. College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, Scotland

    Alexandra Franiek

  2. Department of Pediatrics and Child Health, Children’s Hospital at Health Sciences Center, University of Manitoba, Winnipeg, MB, Canada

    Atul Sharma

  3. SickKids Research Institute, University of Toronto, Toronto, ON, Canada

    Vedran Cockovski

  4. The Metabolomics Innovation Center, University of Alberta, Edmonton, AB, Canada

    David S. Wishart

  5. Department of Pediatrics, Division of Nephrology, Montreal Children’s Hospital, McGill University Health Centre, Montreal, Québec, Canada

    Michael Zappitelli

  6. Department of Pediatrics, University of British Columbia, BC Children’s Hospital, Vancouver, BC, Canada

    Tom D. Blydt-Hansen

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  1. Alexandra Franiek
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  2. Atul Sharma
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Contributions

The following authors were involved in conceiving the research concept and approving the final manuscript: TBH, MZ, and AS. Analysis and results reporting was completed by AS, TBH, VC, and AF. The manuscript was drafted by AF.

Corresponding author

Correspondence to Tom D. Blydt-Hansen.

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Ethics approval

Research ethics board approval was obtained from the University of British Columbia. In the primary studies, research ethics board approval was obtained to perform research activities at all participating institutions.

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Informed consent (and child assent when appropriate) in the original studies was obtained and included consent to utilize frozen biologic specimens for future analyses.

Consent for publication

Patients consented regarding publishing their data as per primary studies.

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The authors declare no competing interests.

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Franiek, A., Sharma, A., Cockovski, V. et al. Urinary metabolomics to develop predictors for pediatric acute kidney injury. Pediatr Nephrol 37, 2079–2090 (2022). https://doi.org/10.1007/s00467-021-05380-6

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  • DOI: https://doi.org/10.1007/s00467-021-05380-6

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