Growth factors VEGF and TGF-beta 1 in peritoneal dialysis

The morphologic alterations in the kidney and the retina that can be presen t in patients with diabetic microangiopathy are mediated by growth factors. Vascular endothelial growth factor (VEGF) is a mediator of neoangiogenesis in diabetic retinopathy. Transforming growth factor-beta (TGF-beta) is inv olved in the extracellular matrix proliferation in diabetic nephropathy. Th e aim of the present study was to investigate the presence of VEGF and TGF- beta 1 in peritoneal effluents of patients undergoing continuous ambulatory peritoneal dialysis who are being treated with glucose-containing dialysis solutions In relation to parameters of peritoneal transport. Standard peri toneal permeability analyses with 3.86% glucose dialysate were performed in 16 stable patients undergoing peritoneal dialysis (PD) (median duration of PD 39 months, range 1 to 104 months). The power relationship that is prese nt between dialysate/serum (D/S) ratios of serum proteins that are transpor ted only across the peritoneal membrane and their molecular weights was use d to predict the D/S ratios when diffusion would be the only explanation fo r the measured dialysate concentration. It was assumed that all TGF-beta 1 in the circulation was bound to alpha 2-macroglobulin. The D/S ratios of VE GF (P < .0005) and TGF-beta 1 (P < .015) were significantly higher than exp ected when VEGF and TGF-beta I would have been transported from the circula tion only by diffusion. No relationship was present between the effluent co ncentration attributed to the local production of VEGF (LVEGF) and that of TGF-beta 1 (LTGF-beta 1). LVEGF correlated with the mass transfer area coef ficient (MTAC) creatinine value (r = 0.69, P < .007), MTAC urate value (r = 0.60, P < .02), and glucose absorption value (r = 0.75, P < .004), all ref lections of the peritoneal vascular surface area. A negative correlation wa s observed between the transcapillary ultrafiltration (926 mL/4 h, 394 to 1 262 mL/4 h) and LVEGF (r = -0.52, P < .045). This negative tendency was als o observed between the net ultrafiltration (622 mL/4 h, -43 to 938 mL/4 h) and LVEGF (r = -0.48) but did not reach significance. LVEGF and the duratio n of treatment did not correlate, possibly because of the relatively small number of patients. LTGF-beta 1 showed no relationship with transport param eters or duration of treatment. In conclusion, we found evidence for the lo cal production of both VEGF and TGF-beta 1 in the peritoneal membrane of pa tients undergoing long-term peritoneal dialysis with glucose-based dialysat e solutions. The analogy with VEGF in diabetic retinopathy suggests a patho genetic role of high dialysate glucose concentrations in the development of these alterations in the peritoneal membrane.