Single-cell transcriptomic reveals the peritoneal microenvironmental change in long-term peritoneal dialysis patients with ultrafiltration failure.

The microenvironmental changes in peritoneal dialysis effluent (PDE) after long-term vintage (LV) of PD in patients with ultrafiltration failure (LV_UF) are unclear. Single-cell sequencing revealed that peritoneal neutrophils were elevated in LV_UF patients, while MRC1-macrophage subcluster decreased compared with PD patients with short vintage (SV) and LV without ultrafiltration failure (LV_NOT_UF). Compared with the LV_NOT_UF group, the upregulated differentially expressed genes (DEGs) of monocytes/macrophages in the LV_UF group were involved in inflammatory response and EMT progress. LV_UF patients had a higher proportion of epithelial-like mesothelial cells (E-MCs), which were characterized by autophagy activation, inflammation, and upregulation of neutrophil- and autophagy-related DEGs compared to the LV_NOT_UF group. Additionally, mesenchymal-like MCs and AQP1 expression were reduced in the LV_UF group compared with the other groups. Both neutrophils and monocytes/macrophages interacted with MCs. Our study provides insights into the roles of peritoneal mesothelial cells and inflammatory cells in PD patients with UF.