Effect of Neutral pH Icodextrin Peritoneal Dialysis Fluid on Mesothelial Cells

Conventional acidic icodextrin peritoneal dialysate (CI) has low biocompatibility due to its low pH, and a neutral pH icodextrin dialysate (NI) was developed. The influence of NI on the peritoneum has not been clarified. The effects of the two dialysates on cultured rat mesothelial cells were examined. CI, but not NI, increased alpha-smooth muscle actin, collagen type 1 and 3, and P21 mRNA expressions. CI with neutralized pH did not improve these harmful effects. With NI+ glucose degradation products (GDPs: same concentration as CI), mRNA expressions were comparable to those with NI alone. However, if NI + GDPs was acidified, mRNA levels matched those with CI. The proportion in the G2/M phase of the cell cycle was lower with CI than with NI stimulation. From these results, CI stimulated epithelial-mesenchymal transition, fibrotic changes, inhibited cell growth, and induced cell senescence. These effects were attributed to the combined low pH and high GDPs.