Sulodexide modulates the dialysate effect on the peritoneal mesothelium

Area of Science:

• Nephrology
• Cell Biology
• Biochemistry

Background:

• Peritoneal membrane damage is a primary cause of chronic peritoneal dialysis failure.
• Preserving mesothelial cells (MC) is crucial for peritoneal membrane survival.
• Dialysates may negatively impact MC function, necessitating protective strategies.

Purpose of the Study:

• To evaluate the effect of peritoneal dialysis (PD) fluid on mesothelial cell (MC) gene expression, secretory activity, and protein synthesis.
• To investigate the potential of sulodexide to mitigate the adverse effects of PD fluid on MC.

Main Methods:

• Dialysate effluents from continuous ambulatory peritoneal dialysis (CAPD) patients were collected.
• The effects of dialysate, with and without sulodexide, on MC were assessed regarding oxidative stress, gene expression, and protein synthesis.
• Key inflammatory and fibrotic markers (IL-6, MCP-1, TGF-β, VCAM-1, VEGF) were quantified.

Main Results:

• PD fluid induced oxidative stress and upregulated genes related to inflammation and fibrosis in MC.
• Secretion of IL-6, MCP-1, TGF-β, VCAM-1, and VEGF significantly increased in MC exposed to PD fluid.
• Sulodexide counteracted the dialysate-induced oxidative stress, gene expression changes, and excessive protein/collagen synthesis in MC.

Conclusions:

• Peritoneal dialysis fluid alters MC phenotype towards a pro-inflammatory, pro-fibrotic, and pro-angiogenic state.
• Sulodexide demonstrates a protective effect by reducing the detrimental impact of PD fluid on mesothelial cells.
• Sulodexide holds potential for preserving peritoneal membrane integrity during chronic PD therapy.