scholarly journals The calcium concentration of peritoneal dialysis solution modifies levels of key mediators of peritoneal fibrosis

2020 ◽  
Author(s):  
Chusheng Miao ◽  
Xiangliang Xue ◽  
Li Dai ◽  
Ruiyu Zhao ◽  
Zhangjian Zhao ◽  
...  
2020 ◽  
Vol 245 (11) ◽  
pp. 983-993 ◽  
Author(s):  
Jing Liu ◽  
Yuan Feng ◽  
Cheng Sun ◽  
Wei Zhu ◽  
Qing-Yan Zhang ◽  
...  

Our previous study demonstrated that the mammalian target of rapamycin complex 1 (mTORC1) pathway is activated in peritoneal fibrosis under high glucose condition. This study aimed to investigate whether valsartan inhibits high glucose-induced peritoneal fibrosis via decreasing the activity of the mTORC1 pathway. We used high glucose peritoneal dialysis solution in a mouse peritoneal dialysis model to induce peritoneal fibrosis in vivo and high glucose in human peritoneal mesothelial cells (HPMCs) to stimulate extracellular matrix accumulation in vitro. After injections of peritoneal dialysis solution containing 4.25% glucose for four weeks, mice showed typical features of peritoneal fibrosis, including markedly increased peritoneal thickness, excessive matrix deposition, increased peritoneal permeability, and higher expression of extracellular matrix proteins, such as α-smooth muscle actin (α-SMA) and collagen I. Oral gavage of valsartan significantly ameliorated these pathological changes at both week 6 and week 8. These effects of valsartan were closely correlated with a decrease in the activation of the mTORC1 signal, which was mediated by the downregulation of the protein expression of phosphorylated (p)-mTOR, p-eukaryotic initiation factor 4E-binding protein 1, and p-p70 S6 kinase 1. Further research showed that the protein expression of mTORC1 signal was positively correlated with the expression of both α-SMA and collagen I in the peritoneum. In vitro, high glucose increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly inhibited high glucose-induced extracellular matrix accumulation in HPMCs. The effect was also accompanied by a decrease in the activation of the mTORC1 signal. Furthermore, the mTOR agonist MHY1485 reversed the downregulation of extracellular matrix components in HPMCs, even in the presence of valsartan. We conclude that valsartan exerts a protective effect against high glucose-induced peritoneal fibrosis via suppressing the activity of the mTORC1 pathway. Impact statement Our study provided new insight into the mechanism underlying the preservation of the peritoneum by valsartan. The results demonstrated that the mice receiving chronic high glucose (HG) peritoneal dialysis solution infusion showed a typical feature of peritoneal fibrosis (PF), as well as higher expression of α-smooth muscle actin (α-SMA) and collagen I. In vitro, HG increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly ameliorated these pathological changes. Interestingly, there was a parallel decrease in the activity of mammalian target of rapamycin complex 1 (mTORC1) and the protein expression levels of α-SMA and collagen I upon treatment with valsartan in vivo and in vitro. Moreover, the mTOR agonist MHY1485 reversed the downregulation of α-SMA and collagen I in vitro, even in the presence of valsartan. Altogether, our findings reported for the first time that valsartan exerts a protective effect against HG-induced PF by inhibiting the activity of the mTORC1 pathway.


ASAIO Journal ◽  
1992 ◽  
Vol 38 (3) ◽  
pp. M585-M588 ◽  
Author(s):  
SILVIA CAROZZI ◽  
MARIA GRAZIA NASINI ◽  
ALBERTO CANTALUPPI ◽  
MARC SALIT

1993 ◽  
Vol 13 (2_suppl) ◽  
pp. 41-43 ◽  
Author(s):  
Silvia Carozzi ◽  
Maria Grazia Nasini

Peritoneal fibrosis remains one of the major causes of dropout In continuous ambulatory peritoneal dialysis (CAPD), because it reduces ultrafiltration capacity. Since studies In vitro have demonstrated that cytoplasmic Ca2+ regulates the proliferation of most cell lines and the release of cytokines from immune cells, we evaluated In 8 uremic patients at the start of CAPD and in 4 control patients the effects in vitro of different peritoneal dialysis solution Ca concentrations (1, 1.25, 1.75, and 2 mmol/L) on peritoneal fibroblast (PF) proliferation, peritoneal macrophages (PMΦ), and peritoneal lymphocyte (Ply) release of interleukin-1 (11–1) and Interferon-gamma (IFN-gamma) (cytokines which are known to induce PF proliferation), and cytoplasmic Ca2+ concentration in PF, PMΦ, and Ply. Results showed that in both the uremic and control patients, increasing the dose of Ca2+ In the medium induced a dose-dependent increase in PF proliferation and the release of IL-1 and IFN-gamma from PMΦ and Ply. Meanwhile, the cytoplasmic parameters PF, PMΦ, and Ply Ca2+ in the uremic patients were below normal; they exceeded the norm with a Ca2+ concentration of 1.75 and 2 mmol/L and were normal with a Ca2+ concentration of 1.25 mmol/L. These data suggest that In CAPD patients the use of a physiological Ca peritoneal dialysis solution (1 and 1.25 mmol/L) may be useful in reducing the proliferation of PF and the production of IL-1 and IFN-gamma thus preventing peritoneal sclerosis.


2012 ◽  
Vol 27 (4) ◽  
pp. 350-356 ◽  
Author(s):  
Gilberto Baroni ◽  
Adriana Fátima Menegat Schuinski ◽  
Poliana Turmena Berticelli ◽  
Maria Angélica Alexandre da Silva ◽  
Denise Sbrissia e Silva Gouveia ◽  
...  

PURPOSE: To investigate the influence of using simvastatin on the peritoneal fibrosis induced in rats using peritoneal dialysis solution with glucoses 4.25%. METHODS: Prospective controlled study in 20 non-uremic Wistar rats. The animals received a peritoneal infusion of 10 ml/100 g of peritoneal dialysis solution glucose 4.25% on a daily basis. The animals were divided in two groups: experimental and control. The experimental group received simvastatin 4 mg/kg/d, by a gastric tube. The control group did not receive any drug. The follow-up was 21 and 49 days. At the end, one surgical procedure was performed to get histological samples of visceral and parietal peritoneum. The samples were analyzed using Hematoxylin Eosin and Sirius Red, to evaluate the severity of the fibrosis. RESULTS: The analysis showed that the intensity of the fibrosis, the peritoneal thickness and the cell number in experimental and control groups were not statistically significant different in experimental and control groups. CONCLUSION: The simvastatin do not decrease the intensity of fibrosis on the peritoneal membrane that happens on rats on peritoneal dialysis.


2019 ◽  
Vol 109 ◽  
pp. 1327-1338 ◽  
Author(s):  
Ying Zhou ◽  
Jinjin Fan ◽  
Chenfei Zheng ◽  
Peiran Yin ◽  
Haishan Wu ◽  
...  

1994 ◽  
Vol 28 (5) ◽  
pp. 572-576 ◽  
Author(s):  
Leigh M. Vaughan ◽  
Cathy Y. Poon

OBJECTIVE: To examine the stability of ceftazidime, vancomycin, and heparin, alone and in combination, in dialysis solution over six days at three temperatures. DESIGN: Nine 250-mL Dianeal PD-2 dextrose 1.5% bags were prepared with ceftazidime, vancomycin, and heparin alone and in combination at set concentrations of 100 μg/mL, 50 μg/mL, and 1 unit/mL, respectively. Three bags of each mixture were stored at 4, 25, and 37°C. Duplicate samples for analysis were removed from each bag at the following time points: premix, 0, 12, 24, 48, 72, 96, 120, and 144 hours. MAIN OURCOME MEASURES: Each sample was examined visually for signs of cloudiness and precipitation. Each sample was analyzed by stability-indicating HPLC assay for ceftazidime and vancomycin, with stability defined as less than 10 percent degradation of drug overtime. RESULTS: No color change or precipitation was observed in any bag. Vancomycin with or without heparin was stable for 5–6 days at 4, 25, and 37°C. Ceftazidime with and without heparin was stable for 6 days at 4°C, 4 days at 25°C, and less than 12 hours at 37 °C. Vancomycin plus ceftazidime with and without heparin was stable for 6 days at 4 °C and 25°C, and 4–5 days at 37 °C, Ceftazidime plus vancomycin with or without heparin was stable for 6 days at 4°C, 2–3 days at 25°C, and 12 hours at 37 °C. CONCLUSIONS: Bulk preparations of ceftazidime and vancomycin, alone and in combination and with or without heparin in Dianeal PD dextrose 1.5% solution, are sufficiently stable for use up to 6 days under refrigeration or 48 hours at room temperature.


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