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Plasma proteomics of acute tubular injury

Author

Listed:
  • Insa M. Schmidt

    (Boston University Chobanian & Avedisian School of Medicine
    Boston Medical Center
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Aditya L. Surapaneni

    (New York University Langone School of Medicine)

  • Runqi Zhao

    (Boston University Chobanian & Avedisian School of Medicine
    Boston Medical Center)

  • Dhairya Upadhyay

    (New York University Langone School of Medicine)

  • Wan-Jin Yeo

    (New York University Langone School of Medicine)

  • Pascal Schlosser

    (Johns Hopkins Bloomberg School of Public Health
    Faculty of Medicine and Medical Center - University of Freiburg
    University of Freiburg)

  • Courtney Huynh

    (Boston University Chobanian & Avedisian School of Medicine
    Boston Medical Center)

  • Anand Srivastava

    (University of Illinois Chicago)

  • Ragnar Palsson

    (Massachusetts General Hospital)

  • Taesoo Kim

    (Massachusetts General Hospital)

  • Isaac E. Stillman

    (Icahn School of Medicine at Mount Sinai)

  • Daria Barwinska

    (Indiana University School of Medicine)

  • Jonathan Barasch

    (Columbia University Irving Medical Center)

  • Michael T. Eadon

    (Indiana University School of Medicine)

  • Tarek M. El-Achkar

    (Indiana University School of Medicine)

  • Joel Henderson

    (Boston University Chobanian & Avedisian School of Medicine)

  • Dennis G. Moledina

    (Yale School of Medicine)

  • Sylvia E. Rosas

    (Harvard Medical School)

  • Sophie E. Claudel

    (Boston University Chobanian & Avedisian School of Medicine
    Boston Medical Center)

  • Ashish Verma

    (Boston University Chobanian & Avedisian School of Medicine
    Boston Medical Center)

  • Yumeng Wen

    (Johns Hopkins University School of Medicine)

  • Maja Lindenmayer

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Tobias B. Huber

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Samir V. Parikh

    (The Ohio State University Wexner Medical Center)

  • John P. Shapiro

    (The Ohio State University Wexner Medical Center)

  • Brad H. Rovin

    (The Ohio State University Wexner Medical Center)

  • Ian B. Stanaway

    (University of Washington School of Medicine)

  • Neha A. Sathe

    (University of Washington School of Medicine)

  • Pavan K. Bhatraju

    (University of Washington School of Medicine
    University of Washington School of Medicine)

  • Josef Coresh

    (New York University Langone School of Medicine)

  • Eugene P. Rhee

    (Massachusetts General Hospital)

  • Morgan E. Grams

    (New York University Langone School of Medicine)

  • Sushrut S. Waikar

    (Boston University Chobanian & Avedisian School of Medicine
    Boston Medical Center)

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.

Suggested Citation

  • 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 Ba, 2024. "Plasma proteomics of acute tubular injury," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51304-x
    DOI: 10.1038/s41467-024-51304-x
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    1. Blue B. Lake & Rajasree Menon & Seth Winfree & Qiwen Hu & Ricardo Melo Ferreira & Kian Kalhor & Daria Barwinska & Edgar A. Otto & Michael Ferkowicz & Dinh Diep & Nongluk Plongthongkum & Amanda Knoten , 2023. "An atlas of healthy and injured cell states and niches in the human kidney," Nature, Nature, vol. 619(7970), pages 585-594, July.
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