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

Abstract

In a previous study, vascular endothelial growth factor (VEGF) was found to be locally produced in the peritoneal tissue of patients undergoing peritoneal dialysis (PD) who were being treated with glucose-containing PD solutions. Locally produced VEGF (LVEGF) was positively related to the mass transfer area coefficient (MTAC) of creatinine and to glucose absorption, both of which are representative of the peritoneal vascular surface area. It was therefore hypothesized that VEGF is involved in the peritoneal neoangiogenesis 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 glucose-based PD solutions during longitudinal follow-up. We also studied the effect of the switch to glucose-free PD treatment on VEGF production. Forty standard peritoneal permeability analyses (SPAs) with 3.86% glucose-containing dialysis solution were investigated. The SPAs were performed in 10 PD patients 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 patients were initially treated with glucose-containing dialysis solutions. Four patients switched after 114 months of glucose-based PD to glucose-free PD and were followed for 7 months. A PD regimen of icodextrin, glycerol, and amino acid–based dialysis solutions was applied in these patients. Four SPAs 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 peritoneum 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 production of VEGF. LVEGF increased with duration of glucose PD, 11.7 ng/L to 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) was found be-tween the differences in MTAC creatinine between the first and last SPA during glucose-based PD and the difference in LVEGF between these observations. A similar correlation was present between the difference in glucose absorption and the difference in LVEGF (r = 0.85, P <.001). This supports a pathogenetic role of high glucose dialysate concentrations in the development of changes in the peritoneum that are found in long-term PD. Treatment with non-glucose-based PD solutions may inhibit further development of these alterations. (J Lab Clin Med 2001;137:125-32)