Selected Growth Factors in Peritoneal Dialysis: Their Relationship to Markers of Inflammation, Dialysis Adequacy, Residual Renal Function, and Peritoneal Membrane Transport

Abstract

Objectives Markers of chronic inflammation, acute-phase reactants, and growth factors may be concomitantly involved in a number of pathologic processes in the general population and uremic patients. In addition, growth factors may influence peritoneal membrane transport characteristics. However, the association between plasma growth factors, markers of chronic inflammation, and peritoneal membrane transport remains largely unknown. The aim of this study was to evaluate the relationship between plasma levels of selected growth factors [basic fibroblast growth factor (bFGF), transforming growth factor β1 (TGFβ1), vascular endothelial growth factor (VEGF)] and markers of chronic inflammation [interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen] in continuous ambulatory peritoneal dialysis (CAPD) patients. The potential link between the above substances and dialysis adequacy was also explored. Design Single-center, cross-sectional study. Setting Peritoneal Dialysis Unit, Medical Faculty, Jagiellonian University Hospital, Kraków, Poland. Patients 32 stable end-stage renal disease patients (13 M, 19 F; mean age 53.6 ± 13.7 years) on CAPD for a median period of 19.5 months. Patients free from signs and symptoms of any inflammatory disease (including peritonitis) for at least 3 months were included into the study. All patients underwent measurements of dialysis dose [Kt/V, weekly creatinine clearance (wCCr)] and peritoneal solute transport using a standard peritoneal equilibration test (PET). Methods TGFβ1, bFGF, VEGF, and IL-6 were measured with ELISA, CRP was assayed with immunonephelometry, and fibrinogen with Multifibren U reagent (Dade Behring Marburg GmbH, Marburg, Germany). Nephron 97 for Windows software was used to assess dialysis adequacy. Results Significant positive correlations between plasma bFGF and IL-6, as well as fibrinogen concentrations ( R = 0.36, p < 0.05 and R = 0.39, p < 0.05, respectively), were found. VEGF correlated significantly with IL-6 and CRP ( R = 0.65, p < 0.0001 and R = 0.51, p < 0.005, respectively). An association between VEGF and bFGF was also found ( R = 0.59, p < 0.0005). Serum level of TGFβ1 revealed no relationship with any marker of acute-phase activation, remaining growth factors, or dialysis adequacy. Positive correlation between TGFβ1 concentration and dialysate-to-plasma ratio for creatinine in PET ( R = 0.35, p < 0.05) was found. In addition, patients with lower solute transport (low/low-average transporters) had lower serum levels of both bFGF and TGFβ1 compared to patients with higher solute transport. Patients with total wCCr > 60 L/week/m2 were characterized by lower levels of bFGF and IL-6. Serum level of IL-6 and plasma levels of bFGF and VEGF were significantly lower among subjects with residual renal function (RRF) > 2.0 mL/minute. Conclusions Our results indicate that systemic inflammation in peritoneal dialysis patients is associated with increased plasma VEGF and bFGF but not TGFβ1. The negative correlation with RRF suggests that either the renal clearance of these cytokines and growth factors may contribute to their elimination, or cytokines and growth factors have a negative impact on RRF. We also suggest an association between serum levels of growth factors tested and peritoneal membrane function.