Acute kidney injury after cardiac surgery is associated with platelet activation.

Abstract

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.