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Abstract: PO0001

Observational Evidence of NAD+ Biosynthetic Impairment and Urinary Metabolomic Alterations in COVID-Related AKI

Session Information

Category: Coronavirus (COVID-19)

  • 000 Coronavirus (COVID-19)

Authors

  • Raines, Nathan H., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Cheung, Matthew David, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Wilson, Landon Shay, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Agarwal, Anupam, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Barnes, Stephen, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Parikh, Samir M., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
Background

Acute kidney injury (AKI) is a frequent extrapulmonary manifestation of COVID-19 and is associated with increased morbidity and mortality. We investigated alterations in the urine metabolome associated with AKI among patients with COVID-19, with the hypothesis that changes in nicotinamide adenine dinucleotide (NAD+) metabolism described in ischemic, toxic, and inflammatory AKI will be also associated with AKI in patients with COVID-19.

Methods

This is a case-control study among two adult populations with COVID-19: critically ill patients hospitalized in Boston, Massachusetts, and a general hospitalized patient population in Birmingham, Alabama. Cases had AKI stages 2 or 3 by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Controls had no AKI by KDIGO criteria. Metabolites were measured by liquid chromatography - mass spectrometry.

Results

14 cases and 14 controls were included from Boston, and 8 cases and 10 controls included from Birmingham. Urinary quinolinate to tryptophan ratio, an indicator which increases with impaired NAD+ biosynthesis, was higher among cases than controls at each location and pooled across locations (median [IQR]: 1.34 [0.59-2.96] in cases, 0.31 [0.13-1.63] in controls, unadjusted p = 0.0013; p=0.03 in analyses adjusted for age and sex). We identified alterations in tryptophan, nicotinamide, and other components of energy metabolism as well as decreases in purine metabolites which contributed to a distinct urinary metabolomic signature that could reliably differentiate patients with and without AKI (supervised random forest class error: 1/14 for AKI and 1/14 for no AKI groups in Boston, 0/8 for AKI and 0/10 for no AKI groups in Birmingham).

Conclusion

Conserved urinary metabolic alterations spanning multiple biochemical pathways distinguish AKI vs. non-AKI in the context of COVID-related hospitalization at two large academic medical centers. AKI is further associated with derangements in NAD+ biosynthesis that suggest impaired energy metabolism in the kidney. Augmenting renal NAD+ by administering biosynthetic precursors may present a novel therapeutic opportunity to mitigate COVID-19 associated AKI.

Funding

  • NIDDK Support