scholarly journals New Developments in Peritoneal Fibroblast Biology: Implications for Inflammation and Fibrosis in Peritoneal Dialysis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Janusz Witowski ◽  
Edyta Kawka ◽  
Andras Rudolf ◽  
Achim Jörres
Keyword(s):  
Extracellular Matrix ◽  
Peritoneal Dialysis ◽  
Current Knowledge ◽  
Significant Heterogeneity ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
New Developments ◽  
Peritoneal Inflammation ◽  
Recent Developments

Uraemia and long-term peritoneal dialysis (PD) can lead to fibrotic thickening of the peritoneal membrane, which may limit its dialytic function. Peritoneal fibrosis is associated with the appearance of myofibroblasts and expansion of extracellular matrix. The extent of contribution of resident peritoneal fibroblasts to these changes is a matter of debate. Recent studies point to a significant heterogeneity and complexity of the peritoneal fibroblast population. Here, we review recent developments in peritoneal fibroblast biology and summarize the current knowledge on the involvement of peritoneal fibroblasts in peritoneal inflammation and fibrosis.

scholarly journals Unfavorable Effects of Peritoneal Dialysis Solutions on the Peritoneal Membrane: The Role of Oxidative Stress

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 768
Author(s):  
Stefanos Roumeliotis ◽  
Evangelia Dounousi ◽  
Marios Salmas ◽  
Theodoros Eleftheriadis ◽  
Vassilios Liakopoulos
Keyword(s):  
Oxidative Stress ◽  
Peritoneal Dialysis ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Structural Alterations ◽  
And Function ◽  
Dialysis Solutions ◽  
Harmful Effects

One of the main limitations to successful long-term use of peritoneal dialysis (PD) as a renal replacement therapy is the harmful effects of PD solutions to the structure and function of the peritoneal membrane (PM). In PD, the PM serves as a semipermeable membrane that, due to exposure to PD solutions, undergoes structural alterations, including peritoneal fibrosis, vasculopathy, and neoangiogenesis. In recent decades, oxidative stress (OS) has emerged as a novel risk factor for mortality and cardiovascular disease in PD patients. Moreover, it has become evident that OS plays a pivotal role in the pathogenesis and development of the chronic, progressive injury of the PM. In this review, we aimed to present several aspects of OS in PD patients, including the pathophysiologic effects on the PM, clinical implications, and possible therapeutic antioxidant strategies that might protect the integrity of PM during PD therapy.

scholarly journals T regulatory cells in childhood arthritis – novel insights

2013 ◽  
Vol 15 ◽  
Author(s):  
Anne M. Pesenacker ◽  
Lucy R. Wedderburn
Keyword(s):  
T Cells ◽  
Juvenile Idiopathic Arthritis ◽  
Regulatory T Cells ◽  
T Regulatory Cells ◽  
Current Knowledge ◽  
Autoimmune Arthritis ◽  
Regulatory Cells ◽  
New Developments ◽  
Childhood Arthritis ◽  
Recent Developments

In recent years, there have been many new developments in the field of regulatory T cells (Treg), challenging the consensus on their behaviour, classification and role(s) in disease. The role Treg might play in autoimmune disease appears to be more complex than previously thought. Here, we discuss the current knowledge of regulatory T cells through animal and human research and illustrate the recent developments in childhood autoimmune arthritis (juvenile idiopathic arthritis (JIA)). Furthermore, this review summarises our understanding of the fields and assesses current and future implications for Treg in the treatment of JIA.

scholarly journals Long-term exposure to new peritoneal dialysis solutions: Effects on the peritoneal membrane

2004 ◽  
Vol 66 (3) ◽  
pp. 1257-1265 ◽  
Author(s):  
Siska Mortier ◽  
Dirk Faict ◽  
Casper G. Schalkwijk ◽  
Norbert H. Lameire ◽  
A.N.S. De Vriese
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Membrane ◽  
Dialysis Solutions ◽  
Peritoneal Dialysis Solutions

Pathogenesis of Peritoneal Sclerosis

2005 ◽  
Vol 28 (2) ◽  
pp. 90-96 ◽  
Author(s):  
C. Pollock
Keyword(s):  
Peritoneal Dialysis ◽  
Large Scale ◽  
Clinical Decision Making ◽  
Inflammatory Cells ◽  
Clinical Decision ◽  
Cumulative Exposure ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Histological Data ◽  
The Individual

Peritoneal sclerosis is an almost invariable consequence of peritoneal dialysis. In most circumstances it is “simple” sclerosis, manifesting clinically with an increasing peritoneal transport rate and loss of ultrafiltration capacity. In contrast, encapsulating peritoneal sclerosis is a life threatening and usually irreversible condition, associated with bowel obstruction, malnutrition and death. It is unknown whether common etiological factors underlie the development of these 2 clinically and pathologically distinct forms of peritoneal sclerosis. The majority of studies to date have investigated factors that contribute to “simple” sclerosis, although it remains possible that similar mechanisms are amplified in patients who develop encapsulated peritoneal sclerosis. The cellular elements that promote peritoneal sclerosis include the mesothelial cells, peritoneal fibroblasts and inflammatory cells. Factors that stimulate these cells to promote peritoneal fibrosis and neoangiogenesis, both inherent in the development of peritoneal sclerosis, include cytokines that are induced by exposure of the peritoneal membrane to high concentrations of glucose, advanced glycation of the peritoneal membrane and oxidative stress. The cumulative exposure to bioincompatible dialysate is likely to have an etiological role as the duration of dialysis correlates with the likelihood of developing peritoneal sclerosis. Indeed peritoneal dialysis using more biocompatible fluids has been shown to reduce the development of peritoneal sclerosis. The individual contribution of the factors implicated in the development of peritoneal sclerosis will only be determined by large scale peritoneal biopsy registries, which will be able to prospectively incorporate clinical and histological data and support clinical decision making.

Monitoring of Long-Term Peritoneal Membrane Function

2001 ◽  
Vol 21 (2) ◽  
pp. 225-232 ◽  
Author(s):  
Simon J. Davies
Keyword(s):  
Peritoneal Dialysis ◽  
Solute Transport ◽  
Water Transport ◽  
Drop Out ◽  
Published Data ◽  
Peritoneal Membrane ◽  
Membrane Function ◽  
Technique Survival ◽  
Ultrafiltration Failure

Objective Peritoneal membrane function influences dialysis prescription and clinical outcome and may change with time on treatment. Increasingly sophisticated tools, ranging from the peritoneal equilibration test (PET) to the standard permeability analysis (SPA) and personal dialysis capacity (PDC) test, are available to the clinician and clinical researcher. These tests allow assessment of a number of aspects of membrane function, including solute transport rates, ultrafiltration capacity, effective reabsorption, transcellular water transport, and permeability to macromolecules. In considering which tests are of greatest value in monitoring long-term membrane function, two criteria were set: those that result in clinically relevant interpatient differences in achieved ultrafiltration or solute clearances, and those that change with time in treatment. Study Selection Clinical validation studies of the PET, SPA, and PDC tests. Studies reporting membrane function using these methods in either long-term (5 years) peritoneal dialysis patients or longitudinal observations (> 2 years). Data Extraction Directly from published data. Additional, previously unpublished analysis of data from the Stoke PD Study. Results Solute transport is the most important parameter. In addition to predicting patient and technique survival at baseline, there is strong evidence that it can increase with time on treatment. Whereas patients with initially high solute transport drop out early from treatment, those with low transport remain longer on treatment, although, over 5 years, a proportion develop increasing transport rates. Ultrafiltration capacity, while being a composite measure of membrane function, is a useful guide for the clinician. Using the PET (2.27% glucose), a net ultrafiltration capacity of < 200 mL is associated with a 50% chance of achieving less than 1 L daily ultrafiltration at the expense of 1.8 hypertonic (3.86%) exchanges in anuric patients. Using a SPA (3.86% glucose), a net ultrafiltration capacity of < 400 mL indicates ultrafiltration failure. While there is circumstantial evidence that, with time on peritoneal dialysis, loss of transcellular water transport might contribute to ultrafiltration failure, none of the current tests is able to demonstrate this unequivocally. Of the other membrane parameters, evidence that interpatient differences are clinically relevant (permeability to macro-molecules), or that they change significantly with time on treatment (effective reabsorption), is lacking. Conclusion A strong case can be made for the regular assessment by clinicians of solute transport and ultrafiltration capacity, a task made simple to achieve using any of the three tools available.

Long-Term Peritoneal Dialysis is a Risk Factor of Sclerosing Encapsulating Peritonitis for Children

2000 ◽  
Vol 20 (4) ◽  
pp. 445-451 ◽  
Author(s):  
Yoshinori Araki ◽  
Hiroshi Hataya ◽  
Yuriko Tanaka ◽  
Ryuji Fukuzawa ◽  
Masahiro Ikeda ◽  
...  
Keyword(s):  
Risk Factor ◽  
Peritoneal Dialysis ◽  
Ct Scan ◽  
Clinical Syndrome ◽  
Peritoneal Fibrosis ◽  
Abdominal Ct ◽  
Sclerosing Encapsulating Peritonitis ◽  
Abdominal Ct Scan ◽  
Encapsulating Peritonitis

Objective Sclerosing encapsulating peritonitis (SEP) is a clinical syndrome with a high mortality rate and is a serious complication of peritoneal dialysis (PD). Peritoneal sclerosis (PS) is a histological diagnosis. PS is usually observed in the peritoneal specimens of patients with SEP. Avoiding SEP is considered to be extremely important for pediatric patients who may require long-term PD. In this study, the characteristics of patients with PS were investigated to determine when to perform peritoneal biopsies and how long PD can be performed safely. Design A retrospective single-center study. Setting Tokyo Metropolitan Kiyose Children's Hospital. Patients A total of 109 children younger than 16 years have received chronic PD in our unit since 1981. Among these children, 16 patients had been on PD for more than 5 years (mean 7.4 ± 2.5 years) from May 1992 to March 1999. Peritoneal biopsies were performed in 14 of the 16 patients, who were divided into two groups based on the histological diagnoses: a PS and a peritoneal fibrosis (PF) group. Results The 14 patients were on PD for a mean of 7.8 ± 2.5 years. There were 8 patients with PS and 6 patients with PF. SEP was observed in 2 patients in the PS group. The risk of PS increased with the duration of PD: 57% (8/14) > 5 years, 80% (4/5) > 8 years, and 100% (3/3) > 10 years. All patients in the PS group showed both peritoneal calcifications on abdominal CT scan and poor ultra-filtration at the time of diagnoses. Conclusion Long-term PD was the important risk factor of SEP. If both peritoneal calcification on abdominal CT scan and poor ultrafiltration are observed in a patient on PD more than 5 years, a peritoneal biopsy should be performed. If PS is detected, PD should be discontinued.

Peritoneal Solute Clearances after four Years of Continuous Ambulatory Peritoneal Dialysis (CAPD)

1989 ◽  
Vol 9 (1) ◽  
pp. 75-78 ◽  
Author(s):  
Min Sun Park ◽  
Jean Lee ◽  
Moon Sung Lee ◽  
Seung Ho Baick ◽  
Seung Duk Hwang ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Glucose Absorption ◽  
Peritoneal Membrane ◽  
Vasoactive Agents ◽  
Membrane Function ◽  
Dialysis Solution ◽  
Before And After ◽  
Dialysate Volume

In order to evaluate peritoneal membrane function and responsiveness of peritoneal microcirculation to vasoactive agents in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, we studied peritoneal clearances of urea (Curea) and creatinine (Ccr), protein concentrations in drained dialysate (D PC), peritoneal glucose absorption (% GA), and drained dialysate volume ( VD) before and after nitroprusside (NP) addition to dialysis solution in 17 long-term CAPD patients (mean duration of CAPD: 52 months) and the results were compared to those of 18 patients who were just trained for CAPD (mean duration: 0.6 month). There were no differences in the control (without NP) Curea, Ccr, D PC, %GA, and VD between the new and long-term CAPD patients. Curea, Ccr, and D PC increased significantly with NP in both new and long-term patients. Curea and Ccr with NP were not different between the new and long-term patients but D PC with NP was significantly lower in the long-term CAPD patients. The results of this study suggest that peritoneal solute clearances and the responsiveness of peritoneal microcirculation to NP remain unchanged after four years of CAPD, despite recurrent episodes of peritonitis.

Biological Significance of Reducing Glucose Degradation Products in Peritoneal Dialysis Fluids

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 23-27 ◽  
Author(s):  
Anders Wieslander ◽  
Torbjörn Linden ◽  
Barbara Musi ◽  
Ola Carlsson ◽  
Reinhold Deppisch
Keyword(s):  
Peritoneal Dialysis ◽  
Side Effects ◽  
Host Defense ◽  
Degradation Products ◽  
Biological Significance ◽  
Peritoneal Membrane ◽  
Negative Side ◽  
Glucose Degradation Products ◽  
Negative Side Effects

Carbohydrates are not stable when exposed to energy; they degrade into new molecules. In peritoneal dialysis (PD) fluids, degradation of glucose occurs during the heat sterilization procedure. The biological consequences of this degradation are side effects such as impaired proliferation and impaired host defense mechanisms, demonstrated in vitro for a great variety of cells. Several highly toxic compounds—such as formaldehyde and 3-deoxyglucosone—have been identified in PD fluids. Carbonyl compounds, apart from being cytotoxic, are also well-known promoters of irreversible advanced glycation end-products (AGEs), which might participate in the long-term remodeling of the peritoneal membrane. Various approaches can be used to reduce the formation of glucose degradation products (GDPs) during heat sterilization. Some examples are shortening the sterilization time, lowering the pH, removing catalyzing substances, and increasing glucose concentration. The latter three factors are employed in the multi-compartment bag with a separate chamber containing pure glucose at high concentration and low pH. Gambrosol trio, a PD fluid produced in this way, shows reduced cytotoxicity, normalized host defense reactions, less AGE formation, and reduced concentrations of formaldehyde and 3-deoxyglucosone. Moreover, in the clinical situation, the fluid turns out to be more biocompatible for the patient, causing less mesothelial cell damage, which in the long term could lead to a more intact peritoneal membrane. Conclusion Glucose degradation products in heat-sterilized fluids for peritoneal dialysis are cytotoxic, promote AGE formation, and cause negative side effects for the patient. Using improved and well-controlled manufacturing processes, it is possible to produce sterile PD fluids with glucose as the osmotic agent but without the negative side effects related to GDPs.

scholarly journals Valsartan ameliorates high glucose-induced peritoneal fibrosis by blocking mTORC1 signaling

2020 ◽  
Vol 245 (11) ◽  
pp. 983-993 ◽  
Author(s):  
Jing Liu ◽  
Yuan Feng ◽  
Cheng Sun ◽  
Wei Zhu ◽  
Qing-Yan Zhang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Peritoneal Dialysis ◽  
Protein Expression ◽  
High Glucose ◽  
Collagen I ◽  
Peritoneal Fibrosis ◽  
Dialysis Solution ◽  
Mtorc1 Pathway ◽  
Peritoneal Dialysis Solution

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.

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