Abstract

Long-term peritoneal dialysis can lead to peritoneal fibrosis (PF), which impairs dialysis efficacy and adversely affects patients’ quality of life. This study aimed to investigate the effects of dialysate components on PF and the mechanisms involved. We enrolled 30 peritoneal dialysis patients and analyzed the correlation between their blood glucose, blood pressure, blood calcium levels, and urine pH with PF severity. In addition, we evaluated the relationship between intraperitoneal dialysate dwell time and PF status. Human peritoneal mesothelial cells (HPMCs) were used as an in vitro model of PF and were treated with high glucose (HG), HCl induced low pH, and calcium chloride, respectively. The expression levels of α-smooth muscle actin (aSMA), fibronectin (Fn), collagen 1a1 (Col1a1), collagen 3a1 (Col3a1), and E-Cadherin (E-Ca) were measured to assess the mesothelial to mesenchymal transition (MMT) and fibrosis in HPMCs. Fibrosis-related signaling pathways were also examined to elucidate the underlying mechanisms. Blood glucose, blood pressure, blood calcium levels as well as intraperitoneal dialysate dwell time were positively correlated with PF in peritoneal dialysis patients, whereas urine pH was inversely correlated with PF score. Treatment of HPMCs with HG significantly increased the expression of aSMA (Acta2), Fn, Col1a1 (Col1a1), and Col3a1. By contrast, low pH and high Ca mainly induced pro-inflammatory cytokine expression in HPMCs. Additionally, we found high glucose primarily activated the TGFβ1 signaling pathway in HPMCs. Among the dialysate-related stressors examined in this study, high glucose most consistently promoted MMT-associated fibrogenic responses in mesothelial cells and was accompanied by activation of TGFβ1/Smad signaling. Low pH and elevated calcium primarily elicited inflammatory responses under the experimental conditions used.