Platelet activation is associated with acute kidney injury after cardiac surgery

Abstract

AbstractBackgroundPost-cardiac surgery acute kidney injury (AKI) is common, with high rates of mortality and morbidity. Despite extensive research, there are no reliable biomarkers. We hypothesised that pro-inflammatory changes associated with platelet activation, including circulating extracellular vesicles (EV) and micro-RNA levels, could provide predictive and diagnostic markers for AKI in cardiac surgery patients.MethodsPlasma samples were collected from 95 patients recruited to the MaRACAS study before, immediately after and 6-12, 24 and 48 hours after surgery. EV size distribution and concentrations were measured using NanoSight. EV derivation and platelet and leukocyte activation were measured using flow cytometry. Platelet responsiveness was measured with Multiplate, and circulating soluble biomarkers were measured with a MAGPIX device. Micro-RNA assessment was performed with TaqMan arrays.ResultsIn the 57% (54/95) of patients who developed AKI post-surgery, the numbers of platelet-derived EVs were higher 24 hours after surgery. TaqMan arrays identified miR-668 downregulated before and miR-92a-1, -920, -518a-3p, -133b and -1262 upregulated after surgery in AKI patients. qRT-PCR confirmed these differences for miR-1262. In addition, in AKI patients, platelets were desensitised to ADP 6-12 hours after surgery, independent of the administration of aspirin or P2Y12 antagonists. AKI patients also had more activated platelets 6-12 hours after surgery, more circulating platelet-granulocyte aggregates before and 6-12 and 24 hours after surgery and higher levels of sICAM1 before and 48 hours after surgery.ConclusionsAKI is associated with increased platelet activation, suggesting that alternative platelet inhibition treatments may be renoprotective. Studies in larger cohorts are required to validate these findings.