Vascular Endothelial Growth Factor in Peritoneal Dialysis Patients

Abstract

Vascular endothelial growth factor (VEGF) is a glycoprotein which exerts mitogenic effects on endo thelial cells, enhances neoangiogenesis and microvascular permeability, influences leukocyte kinetics when upreg ulated by hypoxia and high-glucose concentration in experimental conditions and in human pathology. Peritoneal synthesis of VEGF has been demonstrated in patients on peritoneal dialysis (PD) treated with glucose-based dialy sate solutions. The aim of the study was to determine the serum and peritoneal effluent VEGF concentrations in patients on chronic PD and to assess the relationship between age, gender, comorbidities, dialysis modality and vintage, therapy with erythropoiesis stimulating agents (ESA), angiotensin-converting enzyme inhibitors (ACEi) and statins and VEGF concentrations. Data on the use of ACEi, ESA, and statins were collected from patients' medical histories. VEGF was measured in serum and peritoneal effluent using the quantitative sandwich enzyme immunoassay (ELISA) kits (Quantikine® Human VEGF, R&D Systems, USA & Canada). Complete blood count and standard biochemical analyses (serum glucose, urea, creatinine, total protein, albumin, cholesterol, triglycerides, sodium, potassium, chloride, iron, total iron-binding capacity, ferritin, fibrinogen, C-reactive protein, and intact parathyroid hormone) were performed in fasting venous blood samples. Dialysis and residual components of Kt/V and normalized weekly creatinine clearance were calculated based on 24-hour urine and effluent collections. Peritoneal transport type was determined using the peritoneal equilibration test. Samples from 63 PD patients (39 males and 24 females, average age 61.97 ± 11.01 years) were analyzed. The average serum and effluent VEGF concentrations (231.84 ± 173.91 pg/mL and 38.39 ± 49.38 pg/mL, respectively) correlated significantly (p = 0.002). No significant difference was found in serum and effluent VEGF concentrations in relation to demographic characteristics, comorbidities, dialysis modality, therapy with ESA, ACEi, and statins. Patients treated with PD longer than 5 years had significantly higher serum VEGF levels (p < 0.05). Correlation analysis showed a statistically significant relationship between statin therapy and lower effluent VEGF concentration (p = 0.030). Serum VEGF concentration significantly correlated with fibrinogen serum concentration (p = 0.034) and glycemia (p = 0.004). Effluent VEGF concentration significantly correlated with cholesterolemia (p = 0.004). Serum VEGF concentrations were significantly higher in long term PD patients, and peritoneal effluent VEGF concentrations were significantly lower in patients receiving statins, suggesting a protective effect of those drugs on peritoneal membrane.