The association between the vascular endothelial growth factor-to-cancer antigen 125 ratio in peritoneal dialysis effluent and the epithelial-to-mesenchymal transition in continuous ambulatory peritoneal dialysis.
We examined peritoneal growth factors, mesothelial mass, and epithelial-to-mesenchymal transition (EMT) in response to peritoneal exposure to peritoneal dialysate with standard and low concentrations of glucose degradation products (GDPs). We randomized 56 incident continuous ambulatory peritoneal dialysis (CAPD) patients to receive either low-GDP (30 patients) or high-GDP (standard) peritoneal dialysis (PD) solution (26 patients). The effects of the PD solutions on EMT and peritoneal growth factors in overnight dialysate effluent were compared at 1, 6, and 12 months. Assessment of EMT was performed after human peritoneal mesothelial cells (HPMCs) were cultured from overnight effluent. The low-GDP solution group showed significantly higher dialysate levels of cancer antigen 125 (CA125), fibronectin, transforming growth factor beta(TGFbeta)-induced gene product (betaig-h3), and interleukin-6 (IL-6), but the rate of EMT was significantly lower in the low-GDP solution group during the initial 12 months of CAPD treatment. After adjusting peritoneal growth factors for dialysate CA125 concentration, the low-GDP solution group showed significantly lower ratios of fibronectin/CA125, betaig-h3/CA125, IL-6/CA125, TGFbeta/CA125, and vascular endothelial growth factor (VEGF)/CA125 than did patients in the high-GDP (standard) solution group. Factors associated with higher EMT were the type of solution (high in GDPs), the mass of HPMCs (low CA125), and higher VEGF/CA125. Adjustment of dialysate VEGF for effluent CA125 revealed a significant association with EMT. It suggests that fibroblastoid transition from HPMCs could be affected by the intraperitoneal VEGF per unit mass of HPMCs.
Do
Jun-Young
JY
Department of Internal Medicine, Yeungnam University Hospital, Daegu, Korea. jydo@med.yu.ac.kr
Kim
Yong-Lim
YL
Park
Jong-Won
JW
Chang
Kyung-Ae
KA
Lee
Seung-Hyun
SH
Ryu
Dong-Han
DH
Kim
Chan-Duk
CD
Park
Sun-Hee
SH
Yoon
Kyung-Woo
KW
D015415:Biomarkers / Q000378:metabolism; D018394:CA-125 Antigen / Q000032:analysis*; D018929:Cell Culture Techniques; D015314:Dialysis Solutions / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000473:pathology*; D011446:Prospective Studies; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D000099222:betaIG-H3 Protein
D015415:Biomarkers; D018394:CA-125 Antigen; D015314:Dialysis Solutions; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005947:Glucose; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D000099222:betaIG-H3 Protein