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Published on: November 3, 2023
Acute kidney injury after cardiac surgery is associated with platelet activation
Naomi Brown1, Nikol Sullo1, Nathan Tyson2
1Department of Cardiovascular Sciences and National Institute for Health and Care Research Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, UK.
Background:
Postcardiac surgery acute kidney injury (AKI) is common and associated with high mortality and morbidity. Its pathogenesis remains unclear.
Objectives:
To determine if platelet activation, extracellular vesicles (EVs), and microRNA levels are associated with postoperative AKI.
Methods:
Plasma samples from 95 microRNA in Post CArdiac Surgery study patients were collected before, immediately after, and 6 to 12, 24, and 48 hours after surgery. Platelet responsiveness was assessed using a Multiplate aggregometer. Flow cytometry was used to measure platelet and leukocyte activation and for EV derivation. EV size and concentration were analyzed using NanoSight. Circulating biomarkers were measured using immunoassays, and microRNA was analyzed using TaqMan arrays and validated by quantitative real-time polymerase chain reaction.
Results:
AKI occurred in 57% of patients. Platelet-derived EVs increased 24 hours after surgery in AKI patients. Platelets were desensitized to adenosine diphosphate at 6 to 12 hours, independent of aspirin or P2Y12 antagonist use. AKI patients had more activated platelets at 6 to 12 hours, more platelet-granulocyte aggregates before and at 6 to 12 and 24 hours after surgery, and higher soluble ICAM1 levels before and 48 hours after surgery. TaqMan arrays showed miR-668 was downregulated before and miR-92a-1, -920, -518a-3p, -133b, and -1262 were upregulated after surgery in AKI patients. Quantitative real-time polymerase chain reaction confirmed miR-1262 upregulation. Multivariate analysis showed that granulocyte-platelet aggregates were independently associated with AKI before and at 6 to 12 and 24 hours after surgery. Activated glycoprotein IIb/IIIa and adenosine diphosphate were associated with AKI at 6 to 12 and 24 hours and soluble ICAM1 at 48 hours.
Conclusions:
AKI is associated with platelet activation, suggesting alternative platelet inhibition may offer renoprotection. Larger studies are needed to validate these findings.
Insights
Postcardiac surgery acute kidney injury (AKI) is linked to platelet activation and increased extracellular vesicles (EVs). Targeting platelet pathways may offer kidney protection after cardiac surgery.
Area of Science:
- Cardiovascular Surgery
- Nephrology
- Hematology
Background:
- Postcardiac surgery acute kidney injury (AKI) is a frequent complication with significant mortality.
- The underlying mechanisms of AKI following cardiac surgery are not fully understood.
Purpose of the Study:
- To investigate the association between platelet activation, extracellular vesicles (EVs), and microRNA levels in patients who develop AKI after cardiac surgery.
- To identify potential biomarkers for predicting AKI in the postoperative period.
Main Methods:
- Plasma samples from 95 patients undergoing cardiac surgery were analyzed for platelet responsiveness, activation markers, and EVs at multiple time points.
- Flow cytometry and NanoSight were used to quantify platelet and leukocyte activation and EV characteristics.
- MicroRNA expression profiling was performed using TaqMan arrays and validated by quantitative real-time polymerase chain reaction.
Main Results:
- 57% of patients developed AKI.
- AKI was associated with increased platelet-derived EVs, heightened platelet activation, and more platelet-granulocyte aggregates.
- Specific microRNAs (e.g., miR-1262) were found to be upregulated in AKI patients post-surgery.
- Platelet-granulocyte aggregates and soluble ICAM1 levels were independently associated with AKI development.
Conclusions:
- Platelet activation plays a significant role in the pathogenesis of AKI after cardiac surgery.
- These findings suggest that targeting platelet activation pathways could be a potential strategy for renoprotection.
- Further large-scale studies are warranted to confirm these results and explore therapeutic interventions.
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