The presence of glucose degradation products (GDPs) in peritoneal dialysis (PD) fluids has many adverse effects, namely clinically significant abdominal pain or discomfort during infusion, inhibition of cell proliferation, impairment of inflammatory cell function, cytotoxicity, and the induction of vascular endothelial growth factor (VEGF). In a prospective, randomized, controlled trial comparing a low GDP PD solution (pH 7.0, two compartment bag: low GDP) to conventional PD solution (pH 5.5: high GDP), the overnight dialysate levels of the markers of inflammation/wound healing (hyaluronic acid (HA)), mesothelial cell mass/membrane integrity (cancer antigen 125 (CA125)), and angiogenesis (VEGF) were assessed over a 12-month period. Twenty-six newly commencing continuous ambulatory peritoneal dialysis (CAPD) patients were randomly assigned to either the Low GDP group (n = 16) or the High GDP group (n = 10). Standard peritoneal permeability analysis for membrane transport characteristics and dialysis adequacy with nutritional status (serum albumin, nPCR) were evaluated at 1, 6, and 12 months. In patients treated with high GDP solution, there was significant increase in VEGF with time (time = 1 month, 67.2 +/- 10.8; time = 6 months, 189.8 +/- 90.2; and time = 12 months, 169.3 +/- 83.1 pg/mg of protein; P < 0.05). There was no significant change of VEGF with time in the low GDP group. Significantly higher concentrations of CA125 (65.5 +/- 10.4 vs. 19.7 +/- 2.6 at 1 month, P < 0.0001; 66.6 +/- 9.8 vs. 29.7 +/- 5.0 at 6 months, P < 0.01; 68.7 +/- 10.5 vs. 30.7 +/- 10.0 U/mL at 12 months, P < 0.01) and lower concentrations of HA (114.6 +/- 18.8 vs. 254.3 +/- 69.2 at 1 month, P < 0.05; 417.5 +/- 57.2 vs. 1277.5 +/- 367.9 ng/mg of protein at 12 month, P < 0.05) were observed in the low GDP group compared with the high GDP group. In conclusion, continuous therapy with the low GDP solution modulates the levels of surrogate markers of peritoneal inflammation, integrity and angiogenesis. The results strongly suggest that the use of a low GDP solution would be beneficial to maintain the function and structural integrity of the peritoneal membrane.