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