{"doi":"10.1016/j.ekir.2021.09.001","title":"Nicotinamide Adenine Dinucleotide Biosynthetic Impairment and Urinary Metabolomic Alterations Observed in Hospitalized Adults With COVID-19–Related Acute Kidney Injury","abstract":"IntroductionAcute 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.MethodsThis 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.ResultsA 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).ConclusionUrinary 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.","journal":"Kidney International Reports","year":2021,"id":169543,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9602,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":92165,"name":"Matthew Cheung","orcid":"0000-0003-4182-5220","position":1,"is_corresponding":false},{"id":486021,"name":"Landon Wilson","orcid":"0000-0002-0246-6491","position":2,"is_corresponding":false},{"id":548969,"name":"Jeffrey C. Edberg","orcid":null,"position":3,"is_corresponding":false},{"id":104977,"name":"Nathaniel Erdmann","orcid":null,"position":4,"is_corresponding":false},{"id":656977,"name":"Alec A. Schmaier","orcid":"0000-0002-4975-700X","position":5,"is_corresponding":false},{"id":485708,"name":"Taylor F. Berryhill","orcid":null,"position":6,"is_corresponding":false},{"id":552218,"name":"Zachary Manickas-Hill","orcid":"0000-0002-9880-2356","position":7,"is_corresponding":false},{"id":108340,"name":"Jonathan Z. Li","orcid":"0000-0001-9914-9662","position":8,"is_corresponding":false},{"id":108339,"name":"Xu G. Yu","orcid":"0000-0002-8295-884X","position":9,"is_corresponding":false},{"id":267116,"name":"Anupam Agarwal","orcid":"0000-0003-4276-5186","position":10,"is_corresponding":false},{"id":484841,"name":"Stephen Barnes","orcid":"0000-0001-6837-1674","position":11,"is_corresponding":false},{"id":268732,"name":"Samir M. Parikh","orcid":"0000-0002-1038-981X","position":12,"is_corresponding":false},{"id":700564,"name":"Nathan H. Raines","orcid":"0000-0003-3297-9447","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:46:15.560174Z","pmid":"34541422","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}