Peritoneal dialysis solutions disturb the balance of apoptosis and proliferation of peritoneal cells in chronic dialysis model.

The present study investigated variation in apoptosis and proliferation, and the balance between apoptosis and proliferation, for peritoneal mesothelial cells (MCs) after exposure to peritoneal dialysis solution (PDS) in vivo. We implanted 32 male Sprague-Dawley rats (4 groups; n = 8 in each group) with catheters and intraperitoneally infused the animals with 20 mL Dianeal 1.36%, 2.27%, or 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) PDS twice daily for eight consecutive weeks, using saline as a control. At the end of the eighth week, samples of peritoneal membrane were fixed and sliced. Expression of apoptosis was checked with TUNEL kits (Boehringer Mannheim, Mannheim, Germany), and expression of proliferative cell nuclear antigen (PCNA) was checked by immunohistochemistry [streptoavidin-biotin-peroxidase complex (SABC) method]. The ratio of MC apoptosis to proliferation was measured from the same slices using the dual-stain combination of TUNEL and SABC. Cells positive for apoptosis and PCNA were counted for all samples by light microscopy in 50 consecutive grids (10 x by 40). Peritoneal dialysis solution was found to significantly induce MC apoptosis as compared with control at the end of the eighth week. The degree of apoptosis was proportional to the concentration of glucose in the PDS. The 1.36% PDS, but not the 2.27% or 3.86%, significantly stimulated the expression of PCNA. The degree of PCNA expression was negatively related to the glucose concentration of the PDS. The MC apoptosis: PCNA ratio was significantly higher for 3.86% and 2.27% PDS than for the control, but no significant difference was seen between 1.36% PDS and control. We conclude that glucose-based PDS may induce apoptosis and disturb the balance of MC apoptosis and proliferation, and that 1.36% PDS damages the balance less than does 2.27% or 3.86% PDS. These effects may be partly due to pH, calcium, hyperosmolality, and glucose degradation products (GDPs). Loss of balance between MC proliferation and apoptosis--induced by unphysiologic PDS--may be one of the major causes of peritoneal membrane failure during long-term continuous ambulatory peritoneal dialysis.