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Acute kidney injury after cardiac surgery is associated with platelet activation

Naomi Brown, Nikol Sullo Orcid Logo, Nathan Tyson, Bryony Eagle–Hemming, Florence Y. Lai, Sophia Sheikh, Kristina Tomkova, Lathishia Joel–David, Tracy Kumar, Hardeep Aujla, Alison H. Goodall, Gavin J. Murphy, Marcin J. Woźniak Orcid Logo

Journal of Thrombosis and Haemostasis, Volume: 23, Issue: 9, Pages: 2776 - 2789

Swansea University Author: Nikol Sullo Orcid Logo

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DOI (Published version): 10.1016/j.jtha.2025.06.009

Abstract

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: Pla...

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Published in: Journal of Thrombosis and Haemostasis
ISSN: 1538-7836 1538-7836
Published: Elsevier BV 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa70469
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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. 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spelling 2025-10-30T13:42:17.3874647 v2 70469 2025-09-24 Acute kidney injury after cardiac surgery is associated with platelet activation a2c2be54c418e779fd6a010486e1c730 0000-0002-9885-5474 Nikol Sullo Nikol Sullo true false 2025-09-24 MEDS 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. Journal Article Journal of Thrombosis and Haemostasis 23 9 2776 2789 Elsevier BV 1538-7836 1538-7836 acute kidney injury, cell-derived microparticles, microRNAs, surgical procedure, blood platelets 1 9 2025 2025-09-01 10.1016/j.jtha.2025.06.009 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee 2025-10-30T13:42:17.3874647 2025-09-24T14:05:29.3574384 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Naomi Brown 1 Nikol Sullo 0000-0002-9885-5474 2 Nathan Tyson 3 Bryony Eagle–Hemming 4 Florence Y. Lai 5 Sophia Sheikh 6 Kristina Tomkova 7 Lathishia Joel–David 8 Tracy Kumar 9 Hardeep Aujla 10 Alison H. Goodall 11 Gavin J. Murphy 12 Marcin J. Woźniak 0000-0001-5676-8076 13 70469__35507__e3ece5d9081b43ffb279ed21bbc69152.pdf 70469.VoR.pdf 2025-10-30T13:39:29.8912453 Output 2540095 application/pdf Version of Record true ©2025 The Author(s). This is an open access article under the CC BY license. true eng http://creativecommons.org/licenses/by/4.0/
title Acute kidney injury after cardiac surgery is associated with platelet activation
spellingShingle Acute kidney injury after cardiac surgery is associated with platelet activation
Nikol Sullo
title_short Acute kidney injury after cardiac surgery is associated with platelet activation
title_full Acute kidney injury after cardiac surgery is associated with platelet activation
title_fullStr Acute kidney injury after cardiac surgery is associated with platelet activation
title_full_unstemmed Acute kidney injury after cardiac surgery is associated with platelet activation
title_sort Acute kidney injury after cardiac surgery is associated with platelet activation
author_id_str_mv a2c2be54c418e779fd6a010486e1c730
author_id_fullname_str_mv a2c2be54c418e779fd6a010486e1c730_***_Nikol Sullo
author Nikol Sullo
author2 Naomi Brown
Nikol Sullo
Nathan Tyson
Bryony Eagle–Hemming
Florence Y. Lai
Sophia Sheikh
Kristina Tomkova
Lathishia Joel–David
Tracy Kumar
Hardeep Aujla
Alison H. Goodall
Gavin J. Murphy
Marcin J. Woźniak
format Journal article
container_title Journal of Thrombosis and Haemostasis
container_volume 23
container_issue 9
container_start_page 2776
publishDate 2025
institution Swansea University
issn 1538-7836
1538-7836
doi_str_mv 10.1016/j.jtha.2025.06.009
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
active_str 0
description 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.
published_date 2025-09-01T05:33:00Z
_version_ 1856896373970960384
score 11.096068

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