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Series GSE225349 Query DataSets for GSE225349
Status Public on Dec 01, 2023
Title Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection
Organism Homo sapiens
Experiment type Protein profiling by protein array
Summary 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 40 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.
 
Overall design We used serum protein measurements from patients hospitalized with COVID-19. We defined an AKI cohort using proteomic data acquired at the last available timepoint during the hospital course for all individuals. Controls were defined as individuals who developed AKI stage 1 or did not develop AKI during their hospital course. We used the SomaScan discovery platform to quantify levels of protein expression. See https://www.synapse.org/#!Synapse:syn35874390/ for full clinical data and associated metadata including detailed description for process workflow.

Submitter states: The raw data files are .adat files and contain identifiable sample IDs that cannot be deidentified in the adat file. Therefore the raw data files will not be provided.
Web link https://www.nature.com/articles/s43856-023-00307-8
 
Contributor(s) Paranjpe I, Jayaraman P, Su C, Zhou S, Chen S, Thompson R, Del Valle DM, Kenigsberg E, Zhao S, Jaladanki S, Chaudhary K, Ascolillo S, Vaid A, Kumar A, Kozlova E, Paranjpe M, O’Hagan R, Kamat S, Gulamali FF, Kauffman J, Xie H, Harris J, Patel M, Argueta K, Batchelor C, Nie K, Dellepiane S, Scott L, Levin MA, He JC, Suarez-Farinas M, Coca SG, Chan L, Azeloglu EU, Schadt E, Beckmann N, Gnjatic S, Merad M, Kim-Schulze S, Richards B, Glicksberg BS, Charney AW, Nadkarni GN
Citation(s) 37308534
Submission date Feb 15, 2023
Last update date Mar 01, 2024
Contact name Pushkala Jayaraman
E-mail(s) pushkala.jayaraman@cahn.mssm.edu
Organization name Icahn School of Medicine at Mount Sinai
Department Charles Bronfman Institute of Personalized Medicine
Lab AIMS Lab
Street address 1 Gustave Levy Pl
City New York
State/province New York
ZIP/Postal code 10029
Country USA
 
Platforms (1)
GPL33128 SomaScan human discovery v4.1
Samples (1135)
GSM7046011 plasma, subject 0028c054T1
GSM7046012 plasma, subject 005cd7b9T1
GSM7046013 plasma, subject 005cd7b9T12
Relations
BioProject PRJNA935327

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE225349_non-normalized_counts_covid_AKI.txt.gz 5.0 Mb (ftp)(http) TXT
GSE225349_non-normalized_counts_covid_only.txt.gz 26.3 Mb (ftp)(http) TXT
GSE225349_somalogic_protein_ids_validated.csv.gz 160.6 Kb (ftp)(http) CSV
Processed data are available on Series record

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