Senescence Biomarkers CKAP4 and PTX3 Stratify Severe Kidney Disease Patients

Cells. 2024 Sep 26;13(19):1613. doi: 10.3390/cells13191613.

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: acute kidney injury; biomarker; chronic kidney disease; machine learning; senescence.

MeSH terms

  • Acute Kidney Injury / metabolism
  • Aged
  • Biomarkers* / metabolism
  • C-Reactive Protein* / metabolism
  • Cellular Senescence* / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic* / genetics
  • Renal Insufficiency, Chronic* / metabolism
  • Renal Insufficiency, Chronic* / pathology
  • Serum Amyloid P-Component / genetics
  • Serum Amyloid P-Component / metabolism

Substances

  • Biomarkers
  • C-Reactive Protein
  • Serum Amyloid P-Component
  • PTX3 protein

Grants and 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.