Growth factors VEGF and TGF-beta1 in peritoneal dialysis.
The morphologic alterations in the kidney and the retina that can be present 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 involved in the extracellular matrix proliferation in diabetic nephropathy. The aim of the present study was to investigate the presence of VEGF and TGF-beta1 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 peritoneal 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 present between dialysate/serum (D/S) ratios of serum proteins that are transported only across the peritoneal membrane and their molecular weights was used to predict the D/S ratios when diffusion would be the only explanation for the measured dialysate concentration. It was assumed that all TGF-beta1 in the circulation was bound to alpha2-macroglobulin. The D/S ratios of VEGF (P < .0005) and TGF-beta1 (P < .015) were significantly higher than expected when VEGF and TGF-beta1 would have been transported from the circulation only by diffusion. No relationship was present between the effluent concentration attributed to the local production of VEGF (LVEGF) and that of TGF-beta1 (LTGF-beta1). LVEGF correlated with the mass transfer area coefficient (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 reflections of the peritoneal vascular surface area. A negative correlation was observed between the transcapillary ultrafiltration (926 mL/4 h, 394 to 1262 mL/4 h) and LVEGF (r = -0.52, P < .045). This negative tendency was also 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 duration of treatment did not correlate, possibly because of the relatively small number of patients. LTGF-beta1 showed no relationship with transport parameters or duration of treatment. In conclusion, we found evidence for the local production of both VEGF and TGF-beta1 in the peritoneal membrane of patients undergoing long-term peritoneal dialysis with glucose-based dialysate solutions. The analogy with VEGF in diabetic retinopathy suggests a pathogenetic role of high dialysate glucose concentrations in the development of these alterations in the peritoneal membrane.
Zweers
M M
MM
Department of Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
de Waart
D R
DR
Smit
W
W
Struijk
D G
DG
Krediet
R T
RT
D001692:Biological Transport; D002196:Capillaries / Q000378:metabolism; D003404:Creatinine / Q000032:analysis; D003430:Cross-Sectional Studies; D015314:Dialysis Solutions / Q000737:chemistry* / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000097:blood; D005260:Female; D005947:Glucose / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000378:metabolism*; D008222:Lymphokines / Q000032:analysis* / Q000097:blood; D008297:Male; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000098:blood supply / Q000378:metabolism; D012044:Regression Analysis; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000097:blood; D014462:Ultrafiltration; D014508:Urea / Q000032:analysis; D014527:Uric Acid / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015314:Dialysis Solutions; D016228:Endothelial Growth Factors; D008222:Lymphokines; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014527:Uric Acid; D014508:Urea; D003404:Creatinine; D005947:Glucose