Abstract: TH-PO0137
Unraveling Disease Progression Protein Pathways of Adult Cardiac Surgery Associated-AKI over Time
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Varma, Vijayalakshmi, AstraZeneca Pharmaceuticals LP, Gaithersburg, Maryland, United States
- Vito, Ortensia, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Ashenden, Stephanie Kay, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Gunnarsson, Sophie, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Unwin, Robert J., AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Ågren, Rasmus, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- MacPhee, Iain, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Woollard, Kevin, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Pearce, Andy, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Challis, Ben, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
- Himmelfarb, Jonathan, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Bhatraju, Pavan K., University of Washington, Seattle, Washington, United States
Background
Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major postoperative complication linked to increased morbidity, mortality, and hospital stay. This study used plasma proteomics to investigate the still poorly understood temporal dynamics of pathogenic pathways and pathophysiological mechanisms underlying CSA-AKI, aiming to inform targeted preventive strategies.
Methods
Plasma levels of ~3000 proteins were quantified using Olink Explore in 609 samples from cardiac surgery patients (n=60) with AKI risk factors randomized in the US THRASOS study (NCT01830920) placebo arm. Samples were collected at 11 timepoints from pre-operative to 90 days post-surgery. Patients were stratified by KDIGO criteria: no AKI (n=12), stage 1 (n=13), stage 2 (n=32), and stage 3 (n=3). Differential expression analysis was conducted at each timepoint comparing severe AKI (stages 2–3) with no AKI, followed by over-representation analysis (ORA) of significant proteins.
Results
Reactome ORA on significant proteins comparing severe AKI vs. no AKI patients at each timepoint [Figure 1] showed a strong early immune response, shifting from innate (1-hour post-surgery) to adaptive (6-hour post-surgery) immunity, with anti-inflammatory regulation like IL-10 signaling. By day 3 post-surgery, pathway enrichment shifted to metabolic and reparative processes (e.g., IGF transport regulation and uptake by IGFBPs, and post-translational phosphorylation), suggesting recovery onset from AKI-induced injury.
Conclusion
These findings underscore the role of protein profiling in AKI progression pathways and early biomarkers identification. Further validation is needed to confirm these results and inform targeted therapeutic strategies.
Figure 1 – Reactome Over Representation Analysis at each timepoint
Funding
- Commercial Support – AstraZeneca