Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate

Abstract

Peritoneal fibrosis (PF) is an important complication of peritoneal dialysis (PD) therapy that often occurs in association with peritoneal high transport rate and ultrafiltration failure (UFF). To study the possible pathogenic role of connective tissue growth factor (CTGF) in the relationship of PF and UFF, dialysate CTGF contents (n = 178) and tissue CTGF expression (n = 61) were investigated by ELISA, real-time PCR, immunohistochemistry, and in situ hybridization. CTGF production with and without TGF-beta1 stimulation in human peritoneal mesothelial cells (HPMC) from the spent patients' peritoneal dialysate (n = 32) was studied in vitro. The dialysate-to-plasma ratio for creatinine (D/P Cr) was positively correlated to dialysate CTGF concentration and estimated local peritoneal production of CTGF. CTGF mRNA expression was 11.4-fold higher in peritoneal membranes with UFF than in pre-PD renal failure peritoneum and was correlated with thickness of the peritoneum. CTGF protein and mRNA were detected in mesothelium and in fibroblast-like cells. In cultured HPMC, TGF-beta(1)-induced expression of CTGF mRNA was increased at 12 and 24 h and was correlated with D/P Cr. In contrast, bone morphogenic protein-4 mRNA expression was inversely correlated with D/P Cr. Our results suggest that high peritoneal transport state is associated with fibrosis and increased peritoneal CTGF expression and production by mesothelial cells, which can be stimulated by TGF-beta1. Dialysate CTGF concentration could be a biomarker for both peritoneal fibrosis and membrane function. Functional alteration of mesothelial cells may be involved in progression of peritoneal fibrosis in high transport state.

Vascular endothelial growth factor receptor-3 is a novel target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury

“…[5][6][7]23,24 The antibodies used are listed in Supplementary Table 1. Mast cells were evaluated using sections stained with 0.2% toluidine blue.…”

“…RNA preparation and the synthesis of first-strand cDNA were performed as described previously. [5][6][7]23,24 Total RNA (1 μg) was then reverse transcribed. Quantitative real-time PCR (qPCR) analysis was performed with an Applied Biosystems (South San Francisco, CA, USA) Prism 7500HT sequence detection system using TaqMan gene expression assays as described previously.…”

“…18S ribosomal RNA was used as an endogenous control. 5,7,23,24 Assessment of Lymphatic Absorption To assess absorption via the lymphatic vessels, animals that received 2000 μl of 7.5% icodextrin peritoneal dialysis solution into the peritoneal cavity were killed at 4 h after infusion. An accurate drained volume was measured.…”

“…The mean age of all patients was 52.9 ± 10.9 (range, 30 to 70) years, and the mean duration of peritoneal dialysis treatment was 26.1 ± 24.6 (range, 1 to 103) months. 5,23 VEGF-D mRNA Expression in the Human Peritoneum Fifty-four peritoneal tissue samples were obtained from 29 peritoneal dialysis patients and 25 pre-dialysis chronic renal failure patients at the time of peritoneal dialysis catheter insertion. Among the 29 peritoneal dialysis patients, 7 were regarded as having impaired ultrafiltration capacity, which was defined as described previously.…”

“…Among the 29 peritoneal dialysis patients, 7 were regarded as having impaired ultrafiltration capacity, which was defined as described previously. 5,23,27 Twenty-two patients (incident) had their catheters removed because of transplantation, severe exit site infection, mental disorders, or difficulty in performing the bag exchanges (Table 1).…”