P1146ENHANCED EXPRESSION OF THIOREDOXIN-INTERACTING-PROTEIN (TXNIP) MAY REGULATE OXIDATIVE DAMAGE IN PERITONEAL DIALYSIS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tina Oberacker ◽  
Severin Schricker ◽  
Moritz Schanz ◽  
Dominik M Alscher ◽  
Markus Ketteler
Keyword(s):  
Peritoneal Dialysis ◽  
Oxidative Damage ◽  
Protein Expression ◽  
Mrna Expression ◽  
High Glucose ◽  
Healthy Controls ◽  
Peritoneal Membrane ◽  
Membrane Function ◽  
Dialysis Solutions ◽  
Peritoneal Dialysis Solutions

Abstract Background and Aims Glucose-based solutions used as peritoneal dialysis fluids influence the peritoneal membrane. Exposure to high glucose-based peritoneal dialysis solutions induces reactive oxygen species (ROS) production due to upregulation of TXNIP as shown by several studies in rats as well as in human primary cells. Enhanced expression of TXINP also regulates oxidative damage. Therefore the aim of this study was to investigate the expression of TXNIP and the extent of oxidative damage in human peritoneal biopsies. Method Human peritoneal biopsies of healthy controls, PD patients and patients with EPS were collected. TXNIP and thioredoxin-1 (TRX) mRNA expression was determined by qPCR. Protein expression and the extent of oxidative damage were examined by immunohistochemistry. Results Biopsies from the peritoneum of 7 healthy controls, 36 patients on PD without signs of EPS as well as of 12 patients with EPS were collected. The age of the healthy controls was higher (median 64.00 years, IQR: 53.00-70.00) than in the other subgroups (PD: median 60.50 years, IQR: 46.00-69.00 and EPS: median 51.00 years, IQR: 38.00-58.75). Furthermore, compared to the PD- (39 %) and EPS-group (33 %), there were more female participants in the control-group (86 %). Time on PD was longer in EPS patients (median 70.00 months) than in PD patients (median 33.50 months). In a preliminary study, exposure to high glucose-based peritoneal dialysis solutions did not markedly influence the mRNA expression of TXNIP and TRX. However, on protein level a significant glucose-related upregulation of TXNIP could be observed especially in PD patients. Interestingly, there was no glucose-related change in protein expression of its interacting partner and cellular anti-oxidant TRX. To study the effect of TXNIP expression on the generation of oxidative damage, pH2AX positive nuclei were counted on peritoneal membrane sections. A slight increase of pH2AX positive nuclei upon exposure to dialysis solutions could be observed in the cohort analysed. Conclusion Here, we show for the first time a clear tendency for upregulation TXNIP in human peritoneal tissue after exposure to high glucose-based peritoneal dialysis solutions especially in PD patients. This increase in TXNIP expression may correlate with the accumulation of oxidative damage of macromolecules. Therefore, manipulation of TXNIP expression may be a promising therapeutic target to improve peritoneal membrane function.

MO900ENHANCED EXPRESSION OF THIOREDOXIN-INTERACTING PROTEIN (TXNIP) RESULTS IN REDUCED TRX ACTIVITY AND INCREASED OXIDATIVE DNA-DAMAGE IN PERITONEAL DIALYSIS PATIENTS*

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Tina Oberacker ◽  
Severin Schricker ◽  
Moritz Schanz ◽  
Dominik M Alscher ◽  
Markus Ketteler
Keyword(s):  
Dna Damage ◽  
Peritoneal Dialysis ◽  
Protein Expression ◽  
High Glucose ◽  
Oxidative Dna Damage ◽  
Control Group ◽  
Healthy Controls ◽  
Plasma Samples ◽  
Peritoneal Membrane ◽  
Uremic Patients

Abstract Background and Aims Peritoneal dialysis (PD) is an effective method of renal replacement therapy (RRT). The long-term use of PD as a RRT is limited due to adverse effects of high glucose-based PD solutions to the structure and function of the peritoneal membrane. PD patients show excessive oxidative stress compared to healthy controls. However, there are only scare information on pathophysiological mechanisms leading to oxidative DNA-damage in PD patients. Therefore, the aim of this study was to elucidate the mechanism leading to excessive oxidative stress in human samples of the peritoneal membrane. Method Human peritoneal biopsies of healthy controls, PD patients and patients with EPS were collected. Protein expression of TXNIP was analysed by ELISA using plasma samples and by immunohistochemistry of peritoneal biopsies using a Histo-Score. Protein expression of TRX was examined by immunohistochemistry. To measure TRX activity a kit based on the reduction of insulin by reduced TRX was used. The resulting oxidative DNA-damage was investigated by immunohistochemistry using a Histo-Score or by ELISA using plasma samples of patients. Results Biopsies from the peritoneum of 8 healthy controls, 11 uremic patients, 22 patients on PD < 12 months or 29 patients on PD > 12 months and of 13 patients with EPS were collected. The age of the uremic patients was higher (median 65.0 years, IQR: 49.0-75.0) than in the other subgroups (PD < 12 months: median 62.0 years, IQR: 52.25-68.25, PD > 12 months: median 60.0 years, IQR: 39.5-70.5 and EPS: median 51.00 years, IQR: 40.0-57.5). In general, there were more female participants in the control-group (75 %) compared to all other groups (uremic group: 27%, PD < 12 months: 18 %, PD >12 months: 41% and EPS group 33 %). Time on PD was longer in EPS patients (median 72.0 months) than in PD patients (PD <12 months: median 10.0 months and PD > 12 months: 39.0 months). The ELISA study of plasma samples showed that TXNIP is upregulated in all groups compared to healthy controls. Immunohistochemically studies of peritoneal biopsies showed also an upregulation of TXNIP upon exposure to high glucose-based dialysis fluids (PD and EPS group). Interestingly, a glucose-related change in protein expression of its interacting partner and cellular anti-oxidant TRX was only observed in EPS samples. TRX activity in uremic patients was almost unchanged compared to healthy controls except for one patient. However, enhanced TXNIP expression correlated with a reduced activity of TRX in samples of PD as well as EPS patients. Reduced TRX activity resulted in an increase of produced ROS. Therefore, the effect on the generation of oxidative damage was analysed by ELISA of plasma samples and by immunohistochemistry on peritoneal sections. Both analysis showed an increase in the oxidative DNA-damage marker 8-Hydroxydesoxyguanosin (8-OHdG) in all PD samples and samples of EPS patients compared to the control group. Conclusion Here, we show that high glucose-based peritoneal dialysis solutions lead to an upregulation of TXNIP expression in human peritoneal samples. This increase in TXNIP expression reduces the activity of its interacting partner an antioxidant TRX leading to an increase in ROS production and enhanced levels of DNA-damage. In this study, we elucidate for the first time a novel mechanism showing that glucose-dependent upregulation of TXNIP induces a perturbation of the intracellular redox equilibrium leading to alterations of the peritoneal membrane. Therefore, manipulation of TXNIP expression may be a promising therapeutic target to improve peritoneal membrane function.

The Need for Using An Enzymatic Colorimetric Assay in Creatinine Determination of Peritoneal Dialysis Solutions

1990 ◽  
Vol 10 (1) ◽  
pp. 89-92 ◽  
Author(s):  
Liliane Larpent ◽  
Christian Verger
Keyword(s):  
Peritoneal Dialysis ◽  
Reliable Method ◽  
Colorimetric Assay ◽  
Colorimetric Method ◽  
Peritoneal Membrane ◽  
Creatinine Kinetics ◽  
Dialysis Solutions ◽  
Peritoneal Dialysis Solutions ◽  
Enzymatic Test

The fate of the peritoneal membrane on continuous ambulatory peritoneal dialysis (CAPD) is usually evaluated through the modification of its permeability to various solutes as glucose, creatinine, and urea. Therefore, the accuracy of the methods used for measurements of creatinine is of great importance. A particular problem does exist for creatinine determination as it may be influenced by the presence of glucose. We studied a new enzymatic colorimetric method for creatinine determination in peritoneal dialysis solutions which contain high dextrose concentrations. Creatinine was measured in plasma, urine, and dialysate from 18 patients on CAPD and in pure dextrose solutions, with an enzymatic test (Boehringer Mannheim) and with Jaffe's reaction on two different analyzers: Astra (Beckman) and Eris (Merck). Creatinine results were similar with both assays (Jaffe's reaction and enzymatic test) when measured in blood and urine. However the Jaffe's reaction gave higher creatinine results than the enzymatic test (p < 0.001), when assays were performed in peritoneal dialysis solutions and in pure glucose solutions. In addition, it appeared that other components of dialysis solutions, mainly calcium chloride, influenced unpredictably the results of creatinine with the Jaffe's reaction. We conclude that specific enzymatic test is a more accurate and reliable method to evaluate creatinine kinetics through the peritoneal membrane when determined in CAPD solutions.

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

scholarly journals The Influence of Initial Peritoneal Transport Characteristics, Inflammation, and High Glucose Exposure on Prognosis for Peritoneal Membrane Function

2012 ◽  
Vol 32 (6) ◽  
pp. 636-644 ◽  
Author(s):  
M. José Fernández-Reyes ◽  
M. Auxiliadora Bajo ◽  
Gloria Del Peso ◽  
Marta Ossorio ◽  
Raquel Díaz ◽  
...  
Keyword(s):  
Mass Transfer ◽  
Peritoneal Dialysis ◽  
High Glucose ◽  
Peritoneal Membrane ◽  
Transfer Coefficients ◽  
High Exposure ◽  
Membrane Function ◽  
Peritoneal Transport ◽  
Fast Transport ◽  
Glucose Exposure

♦ BackgroundFast transport status, acquired with time on peritoneal dialysis (PD), is a pathology induced by peritoneal exposure to bioincompatible solutions. Fast transport has important clinical consequences and should be prevented.♦ ObjectiveWe analyzed the repercussions of initial peritoneal transport characteristics on the prognosis for peritoneal membrane function, and also whether the influence of peritonitis and high exposure to glucose are different according to the initial peritoneal transport characteristics or the moment when such events occur.♦ MethodsThe study included 275 peritoneal dialysis patients with at least 2 peritoneal function studies (at baseline and 1 year). Peritoneal kinetic studies were performed at baseline and annually. Those studies consist of a 4-hour dwell with glucose (1.5% during 1981 – 1990, and 2.27% during 1991 – 2002) to calculate the peritoneal mass transfer coefficients of urea and creatinine (milliliters per minute) using a previously described mathematical model.♦ ResultsMembrane prognosis and technique survival were independent of baseline transport characteristics. Fast transport and ultrafiltration (UF) failure are reversible conditions, provided that peritonitis and high glucose exposure are avoided during the early dialysis period. The first year on PD is a main determining factor for the membrane's future, and the mass transfer coefficient of creatinine at year 1 is the best functional predictor of future PD history. After 5 years on dialysis, permeability frequently increases, and UF decreases. Icodextrin is associated with peritoneal protection.♦ ConclusionsPeritoneal membrane prognosis is independent of baseline transport characteristics. Intrinsic fast transport and low UF are reversible conditions when peritonitis and high glucose exposure are avoided during the early dialysis period. Icodextrin helps in glucose avoidance and is associated with peritoneal protection.

pH Equilibration with Acetate and Lactate Solutions during Peritoneal Dialysis

1985 ◽  
Vol 5 (2) ◽  
pp. 123-126 ◽  
Author(s):  
Edward T. Cullom ◽  
Harold L. Moore ◽  
Karl D. Nolph ◽  
Rebecca S. Keller
Keyword(s):  
Peritoneal Dialysis ◽  
Prolonged Exposure ◽  
Rate Of Change ◽  
Peritoneal Membrane ◽  
Membrane Function ◽  
Ph Values ◽  
Calcium Bicarbonate ◽  
Intraperitoneal Instillation ◽  
Osmotic Agent ◽  
Dialysis Solutions

Commercial dialysis solutions contain acetate or lactate and have pH values usually below 6.5. Losses of ultrafiltration in CAPD have been more frequent with acetate than with lactate solutions. It has been suggested that a slower increase of pH following intraperitoneal instillation of acetate solutions may produce alterations in membrane function. We compared intraperitoneal equilibration of pH in rats with acetate and lactate solutions. In our rat model pH equilibration rates were similar for acetate and lactate solutions. Commercial peritoneal dialysis solutions contain glucose as an osmotic agent and acetate or lactate as a buffer (1,2). The pH is adjusted to below 6.0 to prevent glucose caramelization during heat sterilization (3). Acetate and lactate are absorbed during peritoneal dialysis and, when metabolized generate bicarbonate (2). Bicarbonate itself is not used in commercial solutions because these solutions also contain calcium and calcium bicarbonate is unstable in solution on storage. Many workers (4–8) have observed that patients on continuous ambulatory peritoneal dialysis (CAPD) with solutions containing acetate suffer losses of ultrafiltration over time. Also encapsulating sclerosing peritonitis is seen more often in association with acetate solutions (9–11). Pedersen et al (12) fear that prolonged exposure to a low pH may irritate the peritoneal membrane and that, during peritoneal dialysis cycles with acetate as the buffer, the pH in the intraperitoneal solution increases more slowly. These studies were undertaken to determine whether, during peritoneal dialysis exchanges, acetate and lactate solutions had the same rate of change of pH.

Effects of Peritoneal Dialysis Solutions on the Peritoneal Membrane: Clinical Consequences

2005 ◽  
Vol 25 (3_suppl) ◽  
pp. 31-34 ◽  
Author(s):  
Janusz Witowski ◽  
Achim Jörres
Keyword(s):  
Peritoneal Dialysis ◽  
Clinical Significance ◽  
Peritoneal Membrane ◽  
Clinical Consequences ◽  
Dialysis Solutions ◽  
Dialysis Fluids ◽  
Peritoneal Dialysis Solutions

This review provides an overview of recent studies that show the clinical significance of biocompatibility of peritoneal dialysis fluids.

Effects of Peritoneal Dialysis Solutions on the Secretion of Growth Factors and Extracellular Matrix Proteins by Human Peritoneal Mesothelial Cells

2002 ◽  
Vol 22 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Hunjoo Ha ◽  
Mi Kyung Cha ◽  
Hoo Nam Choi ◽  
Hi Bahl Lee
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Mesothelial Cells ◽  
Dependent Manner ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells ◽  
Dialysis Solutions ◽  
Peritoneal Dialysis Solutions

♦ 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.

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