Nicotinamide Adenine Dinucleotide Biosynthetic Impairment and Urinary Metabolomic Alterations Observed in Hospitalized Adults With COVID-19–Related Acute Kidney Injury

Nathan H. Raines, Matthew D. Cheung, Landon S. Wilson, Jeffrey C. Edberg, Nathaniel B. Erdmann, Alec A. Schmaier, Taylor F. Berryhill, Zachary Manickas-Hill, Jonathan Z. Li, Xu G. Yu, Anupam Agarwal, Stephen Barnes, Samir M. Parikh

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Introduction: Acute kidney injury (AKI) is common in COVID-19 and associated with increased morbidity and mortality. We investigated alterations in the urine metabolome to test the hypothesis that impaired nicotinamide adenine dinucleotide (NAD+) biosynthesis and other deficiencies in energy metabolism in the kidney, previously characterized in ischemic, toxic, and inflammatory etiologies of AKI, will be present in COVID-19–associated AKI. Methods: This is a case-control study among the following 2 independent populations of adults hospitalized with COVID-19: a critically ill population in Boston, Massachusetts, and a general population in Birmingham, Alabama. The cases had AKI stages 2 or 3 by Kidney Disease Improving Global Outcomes (KDIGO) criteria; the controls had no AKI. Metabolites were measured by liquid chromatography–mass spectrometry. Results: A total of 14 cases and 14 controls were included from Boston and 8 cases and 10 controls from Birmingham. Increased urinary quinolinate-to-tryptophan ratio (Q/T), found with impaired NAD+ biosynthesis, was present in the cases at each location and pooled across locations (median [interquartile range]: 1.34 [0.59–2.96] in cases, 0.31 [0.13–1.63] in controls, P = 0.0013). Altered energy metabolism and purine metabolism contributed to a distinct urinary metabolomic signature that differentiated patients with and without AKI (supervised random forest class error: 2 of 28 in Boston, 0 of 18 in Birmingham). Conclusion: Urinary metabolites spanning multiple biochemical pathways differentiate AKI versus non-AKI in patients hospitalized with COVID-19 and suggest a conserved impairment in NAD+ biosynthesis, which may present a novel therapeutic target to mitigate COVID-19–associated AKI.

Original languageEnglish (US)
Pages (from-to)3002-3013
Number of pages12
JournalKidney International Reports
Volume6
Issue number12
DOIs
StatePublished - Dec 2021

Keywords

  • COVID-19
  • acute kidney injury
  • metabolism
  • metabolomics
  • nicotinamide adenine dinucleotide (NAD)

ASJC Scopus subject areas

  • Nephrology

Fingerprint

Dive into the research topics of 'Nicotinamide Adenine Dinucleotide Biosynthetic Impairment and Urinary Metabolomic Alterations Observed in Hospitalized Adults With COVID-19–Related Acute Kidney Injury'. Together they form a unique fingerprint.

Cite this