Nicotinamide Adenine Dinucleotide Biosynthetic Impairment and Urinary Metabolomic Alterations Observed in Hospitalized Adults With COVID-19-Related Acute Kidney Injury.
Kidney Int Rep
; 6(12): 3002-3013, 2021 Dec.
Article
in English
| MEDLINE | ID: covidwho-1549765
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Etiology study
/
Observational study
/
Randomized controlled trials
Language:
English
Journal:
Kidney Int Rep
Year:
2021
Document Type:
Article
Affiliation country:
J.ekir.2021.09.001
Similar
MEDLINE
...
LILACS
LIS