Proteomic characterization of acute kidney injury in patients hospitalized with SARS-CoV2 infection
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Published:2023-06-12
Issue:1
Volume:3
Page:
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ISSN:2730-664X
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Container-title:Communications Medicine
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language:en
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Short-container-title:Commun Med
Author:
Paranjpe Ishan, Jayaraman PushkalaORCID, Su Chen-YangORCID, Zhou SiruiORCID, Chen Steven, Thompson RyanORCID, Del Valle Diane Marie, Kenigsberg EphraimORCID, Zhao ShanORCID, Jaladanki SurajORCID, Chaudhary Kumardeep, Ascolillo StevenORCID, Vaid AkhilORCID, Gonzalez-Kozlova EdgarORCID, Kauffman Justin, Kumar ArvindORCID, Paranjpe Manish, Hagan Ross O., Kamat Samir, Gulamali Faris F., Xie Hui, Harris Joceyln, Patel ManishkumarORCID, Argueta Kimberly, Batchelor Craig, Nie Kai, Dellepiane Sergio, Scott Leisha, Levin Matthew A.ORCID, He John CijiangORCID, Suarez-Farinas MayteORCID, Coca Steven G., Chan Lili, Azeloglu Evren U.ORCID, Schadt EricORCID, Beckmann NoamORCID, Gnjatic SachaORCID, Merad MiramORCID, Kim-Schulze Seunghee, Richards BrentORCID, Glicksberg Benjamin S.ORCID, Charney Alexander W.ORCID, Nadkarni Girish N.ORCID
Abstract
Abstract
Background
Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms.
Methods
Using measurements of ~4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N = 437), we identified 413 higher plasma abundances of protein targets and 30 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p < 0.05). Of these, 62 proteins were validated in an external cohort (p < 0.05, N = 261).
Results
We demonstrate that COVID-AKI is associated with increased markers of tubular injury (NGAL) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p < 0.05). Proteins most strongly associated with decreased post-discharge eGFR included desmocollin-2, trefoil factor 3, transmembrane emp24 domain-containing protein 10, and cystatin-C indicating tubular dysfunction and injury.
Conclusions
Using clinical and proteomic data, our results suggest that while both acute and long-term COVID-associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
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