Nature Communications (Aug 2024)
Plasma proteomics of acute tubular injury
- Insa M. Schmidt,
- Aditya L. Surapaneni,
- Runqi Zhao,
- Dhairya Upadhyay,
- Wan-Jin Yeo,
- Pascal Schlosser,
- Courtney Huynh,
- Anand Srivastava,
- Ragnar Palsson,
- Taesoo Kim,
- Isaac E. Stillman,
- Daria Barwinska,
- Jonathan Barasch,
- Michael T. Eadon,
- Tarek M. El-Achkar,
- Joel Henderson,
- Dennis G. Moledina,
- Sylvia E. Rosas,
- Sophie E. Claudel,
- Ashish Verma,
- Yumeng Wen,
- Maja Lindenmayer,
- Tobias B. Huber,
- Samir V. Parikh,
- John P. Shapiro,
- Brad H. Rovin,
- Ian B. Stanaway,
- Neha A. Sathe,
- Pavan K. Bhatraju,
- Josef Coresh,
- the Kidney Precision Medicine Project,
- Eugene P. Rhee,
- Morgan E. Grams,
- Sushrut S. Waikar
Affiliations
- Insa M. Schmidt
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine
- Aditya L. Surapaneni
- Department of Medicine, New York University Langone School of Medicine
- Runqi Zhao
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine
- Dhairya Upadhyay
- Department of Medicine, New York University Langone School of Medicine
- Wan-Jin Yeo
- Department of Medicine, New York University Langone School of Medicine
- Pascal Schlosser
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health
- Courtney Huynh
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine
- Anand Srivastava
- Division of Nephrology, University of Illinois Chicago
- Ragnar Palsson
- Division of Nephrology, Massachusetts General Hospital
- Taesoo Kim
- Division of Nephrology, Massachusetts General Hospital
- Isaac E. Stillman
- Department of Pathology, Icahn School of Medicine at Mount Sinai
- Daria Barwinska
- Division of Nephrology, Indiana University School of Medicine
- Jonathan Barasch
- Department of Pathology, Columbia University Irving Medical Center
- Michael T. Eadon
- Division of Nephrology, Indiana University School of Medicine
- Tarek M. El-Achkar
- Division of Nephrology, Indiana University School of Medicine
- Joel Henderson
- Department of Pathology and Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine
- Dennis G. Moledina
- Department of Internal Medicine, Section of Nephrology, Yale School of Medicine
- Sylvia E. Rosas
- Kidney and Hypertension Unit, Joslin Diabetes Center, Harvard Medical School
- Sophie E. Claudel
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine
- Ashish Verma
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine
- Yumeng Wen
- Division of Nephrology, Johns Hopkins University School of Medicine
- Maja Lindenmayer
- Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf
- Tobias B. Huber
- Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf
- Samir V. Parikh
- Division of Nephrology, The Ohio State University Wexner Medical Center
- John P. Shapiro
- Division of Nephrology, The Ohio State University Wexner Medical Center
- Brad H. Rovin
- Division of Nephrology, The Ohio State University Wexner Medical Center
- Ian B. Stanaway
- Kidney Research Institute, Division of Nephrology, University of Washington School of Medicine
- Neha A. Sathe
- Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington School of Medicine
- Pavan K. Bhatraju
- Kidney Research Institute, Division of Nephrology, University of Washington School of Medicine
- Josef Coresh
- Department of Medicine, New York University Langone School of Medicine
- the Kidney Precision Medicine Project
- Eugene P. Rhee
- Division of Nephrology, Massachusetts General Hospital
- Morgan E. Grams
- Department of Medicine, New York University Langone School of Medicine
- Sushrut S. Waikar
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine
- DOI
- https://doi.org/10.1038/s41467-024-51304-x
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 11
Abstract
Abstract The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ’s metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development. Using the SomaScan proteomics platform on 434 patients with biopsy-confirmed kidney disease, we here identify plasma biomarkers associated with ATI severity. We employ regional transcriptomics and proteomics, single-cell RNA sequencing, and pathway analysis to explore biomarker protein and gene expression and enriched biological pathways. Additionally, we examine ATI biomarker associations with acute kidney injury (AKI) in the Kidney Precision Medicine Project (KPMP) (n = 44), the Atherosclerosis Risk in Communities (ARIC) study (n = 4610), and the COVID-19 Host Response and Clinical Outcomes (CHROME) study (n = 268). Our findings indicate 156 plasma proteins significantly linked to ATI with osteopontin, macrophage mannose receptor 1, and tenascin C showing the strongest associations. Pathway analysis highlight immune regulation and organelle stress responses in ATI pathogenesis.
