Senescence Biomarkers CKAP4 and PTX3 Stratify Severe Kidney Disease Patients

Sean McCallion; Thomas McLarnon; Eamonn Cooper; Andrew R. English; Steven Watterson; Melody El Chemaly; Cathy McGeough; Amanda Eakin; Tan Ahmed; Philip Gardiner; Adrian Pendleton; Gary Wright; Declan McGuigan; Maurice O’Kane; Aaron Peace; Ying Kuan; David S. Gibson; Paula L. McClean; Catriona Kelly; Victoria McGilligan; Elaine K. Murray; Frank McCarroll; Anthony J. Bjourson; Taranjit Singh Rai

doi:10.3390/cells13191613

Senescence Biomarkers CKAP4 and PTX3 Stratify Severe Kidney Disease Patients

Sean McCallion
, Thomas McLarnon
, Eamonn Cooper
, Andrew R. English
, Steven Watterson
, Melody El Chemaly
, Cathy McGeough
, Amanda Eakin
, Tan Ahmed
, Philip Gardiner
, Adrian Pendleton
, Gary Wright
, Declan McGuigan
, Maurice O’Kane
, Aaron Peace
, Ying Kuan
, David S. Gibson
, Paula L. McClean
, Catriona Kelly
, Victoria McGilligan

Elaine K. Murray, Frank McCarroll, Anthony J. Bjourson, Taranjit Singh Rai

Altnagelvin Hospital

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

189 Downloads (Pure)

Abstract

INTRODUCTION: Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage, or metabolic insult. Senescence is associated with ageing and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in acute kidney injury (AKI) and chronic kidney disease (CKD) is not fully understood. However, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated ageing.

METHODS: This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases in controls using OLINK proteomics.

RESULTS: We show that senescence proteins CKAP4 ( p-value < 0.0001) and PTX3 ( p-value < 0.0001) are upregulated in AKI and CKD patients compared with controls with chronic diseases, suggesting the proteins may play a role in overall kidney disease development.

CONCLUSIONS: CKAP4 was found to be differentially expressed in both AKI and CKD when compared to UHCs; hence, this biomarker could be a prognostic senescence biomarker of both AKI and CKD.

Original language	English
Article number	1613
Pages (from-to)	1-18
Number of pages	18
Journal	Cells
Volume	13
Issue number	19
Early online date	26 Sept 2024
DOIs	https://doi.org/10.3390/cells13191613
Publication status	Published (in print/issue) - 26 Sept 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Data Availability Statement

The raw data supporting the conclusions of this article will be made
available by the authors on request.

Funding

This research was mostly funded by a grant to A.J.B. under the EU Regional Development Fund Sustainable Competitiveness Program for NI and the NI Public Health Agency. TSR also acknowledges funding from PHA/HSC R&D Division (COM/5618/20) and the Western Health & Social Care Trust.

Funders	Funder number
Public Health Agency
Western Health & Social Care Trust
HSC R&D Division	COM/5618/20

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

senescence
chronic kidney disease
acute kidney injury
biomarker
machine learning

Access to Document

10.3390/cells13191613

cells-13-01613Final published version, 9.16 MBLicence: CC BY

Cite this

McCallion, S., McLarnon, T., Cooper, E., English, A. R., Watterson, S., Chemaly, M. E., McGeough, C., Eakin, A., Ahmed, T., Gardiner, P., Pendleton, A., Wright, G., McGuigan, D., O’Kane, M., Peace, A., Kuan, Y., Gibson, D. S., McClean, P. L., Kelly, C., ... Rai, T. S. (2024). Senescence Biomarkers CKAP4 and PTX3 Stratify Severe Kidney Disease Patients. Cells, 13(19), 1-18. Article 1613. https://doi.org/10.3390/cells13191613

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title = "Senescence Biomarkers CKAP4 and PTX3 Stratify Severe Kidney Disease Patients",

abstract = "INTRODUCTION: Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage, or metabolic insult. Senescence is associated with ageing and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in acute kidney injury (AKI) and chronic kidney disease (CKD) is not fully understood. However, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated ageing.METHODS: This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases in controls using OLINK proteomics.RESULTS: We show that senescence proteins CKAP4 ( p-value < 0.0001) and PTX3 ( p-value < 0.0001) are upregulated in AKI and CKD patients compared with controls with chronic diseases, suggesting the proteins may play a role in overall kidney disease development. CONCLUSIONS: CKAP4 was found to be differentially expressed in both AKI and CKD when compared to UHCs; hence, this biomarker could be a prognostic senescence biomarker of both AKI and CKD.",

keywords = "senescence, chronic kidney disease, acute kidney injury, biomarker, machine learning",

author = "Sean McCallion and Thomas McLarnon and Eamonn Cooper and English, \{Andrew R.\} and Steven Watterson and Chemaly, \{Melody El\} and Cathy McGeough and Amanda Eakin and Tan Ahmed and Philip Gardiner and Adrian Pendleton and Gary Wright and Declan McGuigan and Maurice O{\textquoteright}Kane and Aaron Peace and Ying Kuan and Gibson, \{David S.\} and McClean, \{Paula L.\} and Catriona Kelly and Victoria McGilligan and Murray, \{Elaine K.\} and Frank McCarroll and Bjourson, \{Anthony J.\} and Rai, \{Taranjit Singh\}",

note = "Publisher Copyright: {\textcopyright} 2024 by the authors.",

year = "2024",

month = sep,

day = "26",

doi = "10.3390/cells13191613",

language = "English",

volume = "13",

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McCallion, S, McLarnon, T, Cooper, E, English, AR, Watterson, S, Chemaly, ME, McGeough, C, Eakin, A, Ahmed, T, Gardiner, P, Pendleton, A, Wright, G, McGuigan, D, O’Kane, M, Peace, A, Kuan, Y, Gibson, DS , McClean, PL , Kelly, C , McGilligan, V , Murray, EK, McCarroll, F, Bjourson, AJ & Rai, TS 2024, 'Senescence Biomarkers CKAP4 and PTX3 Stratify Severe Kidney Disease Patients', Cells, vol. 13, no. 19, 1613, pp. 1-18. https://doi.org/10.3390/cells13191613

TY - JOUR

T1 - Senescence Biomarkers CKAP4 and PTX3 Stratify Severe Kidney Disease Patients

AU - McCallion, Sean

AU - McLarnon, Thomas

AU - Cooper, Eamonn

AU - English, Andrew R.

AU - Watterson, Steven

AU - Chemaly, Melody El

AU - McGeough, Cathy

AU - Eakin, Amanda

AU - Ahmed, Tan

AU - Gardiner, Philip

AU - Pendleton, Adrian

AU - Wright, Gary

AU - McGuigan, Declan

AU - O’Kane, Maurice

AU - Peace, Aaron

AU - Kuan, Ying

AU - Gibson, David S.

AU - McClean, Paula L.

AU - Kelly, Catriona

AU - McGilligan, Victoria

AU - Murray, Elaine K.

AU - McCarroll, Frank

AU - Bjourson, Anthony J.

AU - Rai, Taranjit Singh

PY - 2024/9/26

Y1 - 2024/9/26

N2 - INTRODUCTION: Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage, or metabolic insult. Senescence is associated with ageing and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in acute kidney injury (AKI) and chronic kidney disease (CKD) is not fully understood. However, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated ageing.METHODS: This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases in controls using OLINK proteomics.RESULTS: We show that senescence proteins CKAP4 ( p-value < 0.0001) and PTX3 ( p-value < 0.0001) are upregulated in AKI and CKD patients compared with controls with chronic diseases, suggesting the proteins may play a role in overall kidney disease development. CONCLUSIONS: CKAP4 was found to be differentially expressed in both AKI and CKD when compared to UHCs; hence, this biomarker could be a prognostic senescence biomarker of both AKI and CKD.

AB - INTRODUCTION: Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage, or metabolic insult. Senescence is associated with ageing and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in acute kidney injury (AKI) and chronic kidney disease (CKD) is not fully understood. However, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated ageing.METHODS: This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases in controls using OLINK proteomics.RESULTS: We show that senescence proteins CKAP4 ( p-value < 0.0001) and PTX3 ( p-value < 0.0001) are upregulated in AKI and CKD patients compared with controls with chronic diseases, suggesting the proteins may play a role in overall kidney disease development. CONCLUSIONS: CKAP4 was found to be differentially expressed in both AKI and CKD when compared to UHCs; hence, this biomarker could be a prognostic senescence biomarker of both AKI and CKD.

KW - senescence

KW - chronic kidney disease

KW - acute kidney injury

KW - biomarker

KW - machine learning

UR - https://www.mdpi.com/2073-4409/13/19/1613

UR - https://www.scopus.com/pages/publications/85206275440

U2 - 10.3390/cells13191613

DO - 10.3390/cells13191613

M3 - Article

C2 - 39404377

SN - 2073-4409

VL - 13

SP - 1

EP - 18

JO - Cells

JF - Cells

IS - 19

M1 - 1613

ER -

Senescence Biomarkers CKAP4 and PTX3 Stratify Severe Kidney Disease Patients

Abstract

Bibliographical note

Data Availability Statement

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

A multi-omics analysis of age-associated diseases to identify novel sendotypes

Biomarkers associated with AKI and CKD and their progression

Cite this

Senescence Biomarkers CKAP4 and PTX3 Stratify Severe Kidney Disease Patients

Abstract

Bibliographical note

Data Availability Statement

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Student theses

A multi-omics analysis of age-associated diseases to identify novel sendotypes

Biomarkers associated with AKI and CKD and their progression

Cite this