Plasma Proteomics of Acute Tubular Injury

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Aug 27

PMID 39191768

Authors

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

Eugene P Rhee

Morgan E Grams

Sushrut S Waikar

Affiliations

Soon will be listed here.

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.

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