Changes in Biocompatibility of Dialysis Fluid during Its Dwell in the Peritoneal Cavity

1995 ◽  
Vol 15 (2) ◽  
pp. 152-157 ◽  
Author(s):  
Andrzej Breborowicz ◽  
Leo Martis ◽  
Dimitrios G. Oreopoulos

Objective To evaluate the changes in biocompatibility of peritoneal dialysis solutions during intraperitoneal dwell. Design We studied the effect of the drained dialysates at time 0 and after 30, 60, 120, 240, and 360 minutes of intraperitoneal dwell on the growth of peritoneal mesothelial cells and fibroblasts and the synthesis of proteins by these cells. On one day the patients were dialyzed with glucose-based Dianeal and on alternate days with an amino acid-containing solution based on Travasol. Patients Dialysates were collected from 4 patients during continuous ambulatory peritoneal dialysis (CAPD) training. Results Unused dialysis solutions containing glucose or amino acids inhibit growth of mesothelial cells and fibroblasts. Dialysates obtained after 30 or 60 minutes of intraperitoneal dwell support the growth of these cells in a way similar to 10% fetal calf serum, but dialysates drained after a longer dwell of 120 360 minutes had a stronger effect on growth of these cells than did serum. All glucose-based dialysates stimulate the synthesis of collagen in mesothelial cells, whereas they reduce the synthesis of non-collagen proteins. All glucose-based dialysates reduce the synthesis of collagen and noncollagen proteins in fibroblasts compared with the production of these proteins in the presence of serum. Conclusion Changes in the properties of the dialysis solutions during their intraperitoneal dwells do not seem to increase their biocompatibility. Indeed, excessive mitogenic effect and the stimulation of collagen synthesis of the dialysates may induce pathological changes in the peritoneum.

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Chieko Higuchi ◽  
Junko Kuriyama ◽  
Hiroshi Sakura

Abstract Background Neutral, low-glucose degradation product (GDP) peritoneal dialysis fluid (PDF) is less damaging to the peritoneum than conventional PDF but is still insufficient for biocompatibility. One remaining issue is the problem of buffering. Methods Using cultured rat peritoneal mesothelial cells (PMCs), the present study examined the difference between the effects of neutral low-GDP lactate PDF and neutral low-GDP bicarbonate/lactate PDF on cells. The effects of lactate stimulation on these cells were also examined. Results Lactate PDF enhanced mRNA expressions of α-smooth muscle actin (αSMA) and type 1 and type 3 collagens and lowered expression of e-cadherin mRNA in PMCs compared to bicarbonate/lactate PDF. Lactate stimulation increased mRNA expressions of αSMA, matrix metalloproteinase 2 (MMP2), and basic fibroblast growth factor (bFGF) and suppressed e-cadherin mRNA expression. Transforming growth factor (TGF)-β1 and TGF-β2 and collagen type 1 and 3 mRNA expressions were also enhanced by lactate stimulation. Conclusions These results suggest that lactate as a PDF buffer may act on PMCs to promote epithelial-mesenchymal transition (EMT) and production of TGF-β, bFGF, and collagen.


2002 ◽  
Vol 22 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Hunjoo Ha ◽  
Mi Kyung Cha ◽  
Hoo Nam Choi ◽  
Hi Bahl Lee

♦ Objective To compare the effects of different peritoneal dialysis solutions (PDS) on secretion of vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGFβ1), procollagen I C-terminal peptide (PICP), procollagen III N-terminal peptide (PIIINP), and fibronectin by cultured human peritoneal mesothelial cells (HPMC). ♦ Design Using M199 culture medium as control, commercial PDS containing 1.5% or 4.25% glucose and 40 mmol/L lactate [Dianeal 1.5 (D 1.5) and Dianeal 4.25 (D 4.25), respectively; Baxter Healthcare, Deerfield, Illinois, USA]; PDS containing 1.5% or 4.25% glucose with 25 mmol/L bicarbonate and 15 mmol/L lactate [Physioneal 1.5 (P 1.5) and Physioneal 4.25 (P 4.25), respectively; Baxter]; and PDS containing 7.5% icodextrin [Extraneal (E); Baxter] were tested. Growth-arrested and synchronized HPMC were continuously stimulated for 48 hours by test PDS diluted twofold with M199, TGFβ1 1 ng/mL, or different concentrations of icodextrin. VEGF, TGFβ1, and fibronectin secreted into the media were analyzed by ELISA, and PICP and PIIINP by radioimmunoassay. ♦ Results Dianeal 1.5, D 4.25, and P 4.25, but not P 1.5 and E, significantly increased VEGF secretion compared with control M199. D 4.25- and P 4.25-induced VEGF secretion was significantly higher than induction by D 1.5 and P 1.5, respectively, suggesting that high glucose may be involved in the induction of VEGF. Physioneal 1.5- and P 4.25-induced VEGF secretion was significantly lower than induction by D 1.5 and D 4.25, respectively, suggesting a role for glucose degradation products (GDP) in VEGF production. TGFβ1 secretion was significantly increased by D 4.25 and E. Icodextrin increased TGFβ1 secretion in a dose-dependent manner. All PDS tested significantly increased secretion of PIIINP compared with control. D 1.5- and D 4.25-induced PIIINP secretion was significantly higher than P 1.5, P 4.25, and E. Physioneal 4.25-induced PIIINP secretion was significantly higher than P 1.5, again implicating high glucose and GDP in PIIINP secretion by HPMC. There was no significant increase in PICP or fibronectin secretion using any of the PDS tested. Addition of TGFβ1 1 ng/mL into M199 control significantly increased VEGF, PICP, PIIINP, and fibronectin secretion by HPMC. ♦ Conclusions The present study provides direct evidence that HPMC can secrete VEGF, TGFβ1, and PIIINP in response to PDS, and that HPMC may be actively involved in the development and progression of the peritoneal membrane hyperpermeability and fibrosis observed in long-term PD patients. This study also suggests that both high glucose and GDP in PDS may play important roles in inducing VEGF and PIIINP production/secretion by HPMC.


2020 ◽  
Vol 22 (1) ◽  
pp. 123
Author(s):  
Francesca Piccapane ◽  
Mario Bonomini ◽  
Giuseppe Castellano ◽  
Andrea Gerbino ◽  
Monica Carmosino ◽  
...  

The main reason why peritoneal dialysis (PD) still has limited use in the management of patients with end-stage renal disease (ESRD) lies in the fact that the currently used glucose-based PD solutions are not completely biocompatible and determine, over time, the degeneration of the peritoneal membrane (PM) and consequent loss of ultrafiltration (UF). Here we evaluated the biocompatibility of a novel formulation of dialytic solutions, in which a substantial amount of glucose is replaced by two osmometabolic agents, xylitol and l-carnitine. The effect of this novel formulation on cell viability, the integrity of the mesothelial barrier and secretion of pro-inflammatory cytokines was evaluated on human mesothelial cells grown on cell culture inserts and exposed to the PD solution only at the apical side, mimicking the condition of a PD dwell. The results were compared to those obtained after exposure to a panel of dialytic solutions commonly used in clinical practice. We report here compelling evidence that this novel formulation shows better performance in terms of higher cell viability, better preservation of the integrity of the mesothelial layer and reduced release of pro-inflammatory cytokines. This new formulation could represent a step forward towards obtaining PD solutions with high biocompatibility.


2003 ◽  
Vol 23 (3) ◽  
pp. 222-227 ◽  
Author(s):  
Thomas Sitter ◽  
Matthias Sauter ◽  
Bettina Haslinger

← Objective Hyaluronan (HA) is an important extracellular matrix component and is involved in fluid homeostasis, tissue repair, and response to infections. Previous studies have shown that supplementation of dialysis fluid with high molecular weight HA may have a positive impact on peritoneal solute and fluid transport characteristics. In the present study, we investigated the impact of HA on the synthesis of tissue-type plasminogen activator (t-PA) and its inhibitor, plasminogen activator inhibitor type 1 (PAI-1) in cultured human peritoneal mesothelial cells (MC). ← Methods Cultured human peritoneal MC isolated from omental tissue were used for the experiments. Concentrations of t-PA and PAI-1 antigens were measured in conditioned media of confluent MC using ELISA. Northern blot analysis was performed to investigate mRNA expression of t-PA, PAI-1, and low-density lipoprotein receptor-related protein. ← Results Hyaluronan in a concentration as suggested for supplementation of dialysis fluid (10 mg/dL) did not have a significant impact on the synthesis of t-PA or PAI-1 in human MC. However, incubation of MC with higher concentrations of HA (30 – 1000 mg/dL) resulted in a concentration- and time- (8 – 48 hours) dependent decrease in t-PA antigen release and mRNA expression. In contrast, PAI-1 antigen secretion was distinctly but not significantly increased in the presence of HA. ← Conclusion The expression of t-PA and PAI-1 in MC was not affected by low concentrations of HA. Therefore, it is reasonable to assume that supplementation of dialysis fluid with HA (10 mg/dL) will not decrease mesothelial fibrinolytic activity. Only high concentrations (> 50 mg/dL) may disturb the balance between intraperitoneal generation and degradation of fibrin by decreasing t-PA synthesis.


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