Single-cell immune landscape of acute kidney injury after cardiac surgery with cardiopulmonary bypass.

OBJECTIVES: Acute kidney injury (AKI) occurs in 19-42% of patients with cardiac surgery under cardiopulmonary bypass (CPB). Clarifying their landscape of immune cells may help discover the mechanisms and thus the treatment and preventive strategies. METHODS: This prospective, single center study recruited adult patients scheduled for cardiac surgery. The primary outcome was AKI. Blood samples were harvested from the central vein for single-cell RNA sequencing, flow cytometry and protein microarrays to characterize the landscape of immune cells. Here we compared the single-cell RNA sequencing of 42,362 immune cells in the blood of 4 patients before and after cardiac surgery, depending on whether they experienced AKI or not. RESULTS: We observed an increased degree of stronger activation and cytotoxicity of CD8+ and CD4+ T cells, upregulation of CCL5 and downregulation of IL-10 in patients who experienced AKI than those who did not. Analysis of cell-to-cell communication linked AKI to greater postoperative interaction between CCL5 CD8+ T cells and CCR1 on monocytes, as well as between ICAM1 on monocytes and the complex of ITGAL and integrin β2 on T cells. Furthermore, we also found a positive association between AKI and IL-16 signal as well as stronger signaling involving macrophage migration inhibitory factor (MIF). CONCLUSIONS: To our knowledge, this is the first prospective study to integrate single-cell RNA-seq, flow cytometry, and protein microarray in cardiac surgery-related AKI. Our analysis identified distinct immune cells and identified key biomarkers, including CD69, CD28, CCL5, ICAM1, IL-16 and MIF as candidate pathway.