Vascular endothelial growth factor in peritoneal dialysis: A longitudinal follow-up

In a previous study, vascular endothelial growth factor (VEGF) was found to be locally produced in the peritoneal tissue of patients undergoing perito neal dialysis (PD) who were being treated with glucose-containing PD soluti ons. Locally produced VEGF (LVEGF) was positively related to the mass trans fer area coefficient (MTAC) of creatinine and to glucose absorption, both o f which are representative of the peritoneal vascular surface area. It was therefore hypothesized that VEGF is involved in the peritoneal neoangiogene sis found in long-term PD. The aim of the present study was to investigate the time course of peritoneal VEGF levels in PD patients treated with gluco se-based PD solutions during longitudinal follow-up. We also studied the ef fect of the switch to glucose-free PD treatment on VEGF production. Forty s tandard peritoneal permeability analyses (SPAs) with 3.86% glucose-containi ng dialysis solution were investigated. The SPAs were performed in 10 PD pa tients with a median number of three SPAs per patient during a follow-up of 23 months. Duration of PD treatment at the last SPA was 74 months. All pat ients were initially treated with glucose-containing dialysis solutions. Fo ur patients switched after 114 months of glucose-based PD to glucose-free P D and were followed for 7 months. A PD regimen of icodextrin, glycerol, and amino acid-based dialysis solutions was applied in these patients. Four SP As were performed per patient in this period. To predict the VEGF dialysate -to-serum ratio (D/S), when diffusion would be the only explanation for the VEGF dialysate concentration, we calculated the power relationship between D/S ratios of serum proteins that are only transported across the peritone um and the molecular weights of those proteins. The measured VEGF D/S ratio was higher than expected (P<.001) in each observation, pointing to local p roduction of VEGF. LVEGF increased with duration of glucose PD, 11.7 ng/L t o 23.45 ng/L (P<.03). LVEGF decreased in all 4 patients undergoing glucose- free PD, from 57.35 ng/L to 23.10 ng/L. A correlation (r = 0.83, P<.001) wa s found between the differences in MTAC creatinine between the first and la st SPA during glucose-based PD and the difference in LVEGF between these ob servations. A similar correlation was present between the difference in glu cose absorption and the difference in LVEGF (r = 0.85, P<.001). This suppor ts a pathogenetic role of high glucose dialysate concentrations in the deve lopment of changes in the peritoneum that are found in long-term PD. Treatm ent with non-glucose-based PD solutions may inhibit further development of these alterations.