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Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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Materias: | |
Acceso en línea: | 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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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. |
format | Online Article Text |
id | pubmed-10055503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
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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