Effect of Neutral pH Icodextrin Peritoneal Dialysis Fluid on Mesothelial Cells

Area of Science:

• Nephrology
• Cell Biology
• Biocompatibility Studies

Background:

• Conventional acidic icodextrin peritoneal dialysate (CI) exhibits low biocompatibility due to its acidic pH.
• A neutral pH icodextrin dialysate (NI) has been developed, but its effects on the peritoneum remain unclear.

Purpose of the Study:

• To investigate the impact of conventional acidic icodextrin (CI) and neutral pH icodextrin (NI) dialysates on cultured rat mesothelial cells.
• To determine the specific roles of low pH and glucose degradation products (GDPs) in the observed cellular effects.

Main Methods:

• Cultured rat mesothelial cells were exposed to CI and NI dialysates.
• Gene expression of α-smooth muscle actin, collagen types 1 and 3, and P21 was analyzed using mRNA expression.
• Cell cycle progression was assessed by examining the proportion of cells in the G2/M phase.

Main Results:

• CI significantly increased mRNA expression for α-smooth muscle actin, collagen types 1 and 3, and P21 compared to NI.
• Neutralizing the pH of CI did not mitigate these harmful effects.
• The harmful effects of CI were replicated when NI was combined with glucose degradation products (GDPs) at concentrations found in CI and then acidified.
• CI inhibited cell growth, evidenced by a lower proportion of cells in the G2/M phase of the cell cycle.

Conclusions:

• Conventional acidic icodextrin (CI) dialysate induces epithelial-mesenchymal transition, fibrotic changes, inhibits cell growth, and promotes cell senescence in mesothelial cells.
• These detrimental effects are attributed to the combined influence of low pH and high glucose degradation products (GDPs) in CI.
• Neutral pH icodextrin (NI) demonstrates improved biocompatibility, suggesting it as a potentially safer alternative for peritoneal dialysis.