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; Kidney Precision Medicine Project; Eugene P Rhee; Morgan E Grams; Sushrut S Waikar

doi:10.1038/s41467-024-51304-x

Plasma proteomics of acute tubular injury

Nat Commun. 2024 Aug 27;15(1):7368. doi: 10.1038/s41467-024-51304-x.

Authors

Insa M Schmidt^{1

2

3

4}, Aditya L Surapaneni⁵, Runqi Zhao^{6

7}, Dhairya Upadhyay⁵, Wan-Jin Yeo⁵, Pascal Schlosser^{8

9

10}, Courtney Huynh^{6

7}, Anand Srivastava¹¹, Ragnar Palsson¹², Taesoo Kim¹², Isaac E Stillman¹³, Daria Barwinska¹⁴, Jonathan Barasch¹⁵, Michael T Eadon¹⁴, Tarek M El-Achkar¹⁴, Joel Henderson¹⁶, Dennis G Moledina¹⁷, Sylvia E Rosas¹⁸, Sophie E Claudel^{6

7}, Ashish Verma^{6

7}, Yumeng Wen¹⁹, Maja Lindenmayer^{20

21}, Tobias B Huber^{20

21}, Samir V Parikh²², John P Shapiro²², Brad H Rovin²², Ian B Stanaway²³, Neha A Sathe²⁴, Pavan K Bhatraju^{23

24}, Josef Coresh⁵; Kidney Precision Medicine Project; Eugene P Rhee¹², Morgan E Grams⁵, Sushrut S Waikar^{6

7}

Affiliations

¹ Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. [email protected].
² Section of Nephrology, Boston Medical Center, Boston, MA, USA. [email protected].
³ Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany. [email protected].
⁴ III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. [email protected].
⁵ Department of Medicine, New York University Langone School of Medicine, New York, NY, USA.
⁶ Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
⁷ Section of Nephrology, Boston Medical Center, Boston, MA, USA.
⁸ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁹ Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
¹⁰ Centre for Integrative Biological Signaling Studies (CIBSS), University of Freiburg, Freiburg, Germany.
¹¹ Division of Nephrology, University of Illinois Chicago, Chicago, IL, USA.
¹² Division of Nephrology, Massachusetts General Hospital, Boston, MA, USA.
¹³ Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁴ Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁵ Department of Pathology, Columbia University Irving Medical Center, New York, NY, USA.
¹⁶ Department of Pathology and Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
¹⁷ Department of Internal Medicine, Section of Nephrology, Yale School of Medicine, New Haven, CT, USA.
¹⁸ Kidney and Hypertension Unit, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
¹⁹ Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²⁰ Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
²¹ III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
²² Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
²³ Kidney Research Institute, Division of Nephrology, University of Washington School of Medicine, Seattle, WA, USA.
²⁴ Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington School of Medicine, Seattle, WA, USA.

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.

MeSH terms

Acute Kidney Injury* / blood
Adult
Aged
Biomarkers* / blood
Blood Proteins / metabolism
COVID-19* / blood
Female
Humans
Kidney Tubules / metabolism
Kidney Tubules / pathology
Male
Middle Aged
Osteopontin* / blood
Proteomics* / methods
SARS-CoV-2
Single-Cell Analysis
Tenascin / blood
Tenascin / genetics
Tenascin / metabolism

Substances

Biomarkers
Osteopontin
Tenascin
TNC protein, human
SPP1 protein, human
Blood Proteins

Grants and funding

R01 DK124667/DK/NIDDK NIH HHS/United States