Background: Post-cardiac surgery acute kidney injury (AKI) is common and associated with high mortality and morbidity. Its pathogenesis remains unclear. We hypothesised that platelet activation, extracellular vesicles (EVs), and micro-RNA levels are associated with post-surgery AKI.

Methods: Plasma samples from 95 MaRACAS study patients were collected before, immediately after, and 6-12, 24, and 48 hours post-surgery. Platelet responsiveness was assessed with Multiplate. Flow cytometry measured platelet and leukocyte activation and EV derivation. EV size and concentration were analysed using NanoSight. Circulating biomarkers were measured by immunoassays, and micro-RNA was analysed using TaqMan-arrays and validated by qPCR.

Results: AKI occurred in 57% of patients. Platelet-derived EVs increased 24 hours post-surgery in AKI patients. Platelets were desensitised to ADP at 6-12 hours, independent of aspirin or P2Y12 antagonist use. AKI patients had more activated platelets at 6-12 hours, more platelet-granulocyte aggregates before, and at 6-12 and 24 hours post-surgery, and higher sICAM1 levels before and 48 hours post-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. qRT-PCR confirmed miR-1262 upregulation. Multivariate analysis showed that granulocyte-platelet aggregates were independently associated with AKI before, and at 6-12 and 24 hours post-surgery. Activated GPIIb/IIIa and ADP were associated with AKI at 6-12 and 24 hours, and sICAM1 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.

Keywords: Acute Kidney Injury; Biomarkers; Cardiovascular; Cell-Derived Microparticles; MicroRNAs; Surgical Procedure.

Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.

背景： 心脏手术后的急性肾损伤（AKI）很常见，并且与高死亡率和发病率相关。其发病机制尚不清楚。我们假设血小板激活、细胞外囊泡（EVs）和微RNA水平与术后AKI有关。

方法： 从95名MaRACAS研究患者的血液样本在术前、术后立即以及术后6-12小时、24小时和48小时内采集。使用Multiplate评估血小板的反应性，通过流式细胞术测量血小板和白细胞激活及EV生成。使用NanoSight分析EV大小和浓度。通过免疫测定法检测循环生物标志物，并利用TaqMan阵列和qPCR验证微RNA。

结果： 57%的患者发生AKI。在术后24小时，AKI患者的血小板来源EV水平升高。术后6-12小时内，尽管使用了阿司匹林或P2Y12拮抗剂，血小板对ADP的敏感性降低。AKI患者在术前和术后6-12及24小时内具有更多的活化血小板，并且有更多的血小板-粒细胞聚集体，同时sICAM1水平在术前以及术后48小时升高。TaqMan阵列显示，在手术前后AKI患者的miR-668下调，而miR-92a-1、-920、-518a-3p、-133b和-1262上调。qRT-PCR证实了miR-1262的上调。多变量分析表明，在术前以及术后6-12小时和24小时内，粒细胞-血小板聚集体与AKI独立相关。活化的GPIIb/IIIa及ADP在术后6-12小时和24小时与AKI相关，并且sICAM1在术后48小时与AKI有关。

结论： AKI与血小板激活有关，这表明替代的血小板抑制可能为肾脏保护提供帮助。需要更大的研究来验证这些发现。

关键词： 急性肾损伤；生物标志物；心血管疾病；细胞衍生微颗粒；微RNA；手术程序。