Single-Cell RNA Sequencing Reveals Peritoneal Environment and New Insights into Fibrosis in a Continuous Ambulatory...

Peritoneal fibrosis (PF) from long-term peritoneal dialysis (PD) is one of the main reasons for the ultrafiltration failure and the abandonment of PD in patients, and there is no effective treatment available. The dynamic changes in the PD microenvironment and their relationship to PD-related fibrosis remain unclear.

We performed single-cell RNA sequencing (scRNA-seq) on overnight PD effluent collected from a continuous ambulatory PD (CAPD) patient at two critical time points: the initiation of dialysis and after 3 years of treatment, so as to reveal the dynamic changes of immune cells and peritoneal mesothelial cells (PMCs) during prolonged PD.

The results showed that six distinct populations of cells were identified within the PD effluent. The fibrotic progression exhibited a temporal shift in cellular dynamics: early-stage pathology was characterized by a sustained inflammatory response mediated primarily by macrophages, T cells, and PMCs, while late-stage pathogenesis transitioned to extracellular matrix (ECM) remodeling dominated by PMCs and fibroblasts.

These findings demonstrate that different cell types and microenvironment contribute to initial injury responses and subsequent tissue remodeling of peritoneum, which provides a deeper comprehension for the mechanism in PF.