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author Nadkami, Girish
Paranjpe, Ishan
Jayaraman, Pushkala
Su, Chen-Yang
Zhou, Sirui
Chen, Steven
Valle, Diane Del
Thompson, Ryan
Kenigsberg, Ephraim
Zhao, Shan
Jaladanki, Suraj
Chaudhary, Kumardeep
Ascolillo, Steven
Vaid, Akhil
Gonzalez-Kozlova, Edgar
Kumar, Arvind
Paranjpe, Manish
O’Hagan, Ross
Kamat, Samir
Gulamali, Faris
Kauffman, Justin
Xie, Hui
Harris, Joceyln
Patel, Manishkumar
Argueta, Kimberly
Batchelor, Craig
Nie, Kai
Dellepiane, Sergio
Scott, Leisha
Levin, Matthew
He, John
Suárez-Fariñas, Mayte
Coca, Steven
Chan, Lili
Azeloglu, Evren
Schadt, Eric
Beckmann, Noam
Gnjatic, Sacha
Merad, Miriam
Kim-Schulze, Seunghee
Richards, J. Brent
Glicksberg, Benjamin
Charney, Alexander
author_facet Nadkami, Girish
Paranjpe, Ishan
Jayaraman, Pushkala
Su, Chen-Yang
Zhou, Sirui
Chen, Steven
Valle, Diane Del
Thompson, Ryan
Kenigsberg, Ephraim
Zhao, Shan
Jaladanki, Suraj
Chaudhary, Kumardeep
Ascolillo, Steven
Vaid, Akhil
Gonzalez-Kozlova, Edgar
Kumar, Arvind
Paranjpe, Manish
O’Hagan, Ross
Kamat, Samir
Gulamali, Faris
Kauffman, Justin
Xie, Hui
Harris, Joceyln
Patel, Manishkumar
Argueta, Kimberly
Batchelor, Craig
Nie, Kai
Dellepiane, Sergio
Scott, Leisha
Levin, Matthew
He, John
Suárez-Fariñas, Mayte
Coca, Steven
Chan, Lili
Azeloglu, Evren
Schadt, Eric
Beckmann, Noam
Gnjatic, Sacha
Merad, Miriam
Kim-Schulze, Seunghee
Richards, J. Brent
Glicksberg, Benjamin
Charney, Alexander
author_sort Nadkami, Girish
collection PubMed
description 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-Cindicating 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.
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spelling pubmed-100555032023-03-30 Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection Nadkami, Girish Paranjpe, Ishan Jayaraman, Pushkala Su, Chen-Yang Zhou, Sirui Chen, Steven Valle, Diane Del Thompson, Ryan Kenigsberg, Ephraim Zhao, Shan Jaladanki, Suraj Chaudhary, Kumardeep Ascolillo, Steven Vaid, Akhil Gonzalez-Kozlova, Edgar Kumar, Arvind Paranjpe, Manish O’Hagan, Ross Kamat, Samir Gulamali, Faris Kauffman, Justin Xie, Hui Harris, Joceyln Patel, Manishkumar Argueta, Kimberly Batchelor, Craig Nie, Kai Dellepiane, Sergio Scott, Leisha Levin, Matthew He, John Suárez-Fariñas, Mayte Coca, Steven Chan, Lili Azeloglu, Evren Schadt, Eric Beckmann, Noam Gnjatic, Sacha Merad, Miriam Kim-Schulze, Seunghee Richards, J. Brent Glicksberg, Benjamin Charney, Alexander Res Sq Article 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-Cindicating 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. American Journal Experts 2023-03-16 /pmc/articles/PMC10055503/ /pubmed/36993735 http://dx.doi.org/10.21203/rs.3.rs-2379226/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Nadkami, Girish
Paranjpe, Ishan
Jayaraman, Pushkala
Su, Chen-Yang
Zhou, Sirui
Chen, Steven
Valle, Diane Del
Thompson, Ryan
Kenigsberg, Ephraim
Zhao, Shan
Jaladanki, Suraj
Chaudhary, Kumardeep
Ascolillo, Steven
Vaid, Akhil
Gonzalez-Kozlova, Edgar
Kumar, Arvind
Paranjpe, Manish
O’Hagan, Ross
Kamat, Samir
Gulamali, Faris
Kauffman, Justin
Xie, Hui
Harris, Joceyln
Patel, Manishkumar
Argueta, Kimberly
Batchelor, Craig
Nie, Kai
Dellepiane, Sergio
Scott, Leisha
Levin, Matthew
He, John
Suárez-Fariñas, Mayte
Coca, Steven
Chan, Lili
Azeloglu, Evren
Schadt, Eric
Beckmann, Noam
Gnjatic, Sacha
Merad, Miriam
Kim-Schulze, Seunghee
Richards, J. Brent
Glicksberg, Benjamin
Charney, Alexander
Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection
title Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection
title_full Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection
title_fullStr Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection
title_full_unstemmed Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection
title_short Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection
title_sort proteomic characterization of acute kidney injury in patients hospitalized with sars-cov2 infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055503/
https://www.ncbi.nlm.nih.gov/pubmed/36993735
http://dx.doi.org/10.21203/rs.3.rs-2379226/v1
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