scholarly journals Peritoneal Dialysis Fluid Supplementation with Alanyl-Glutamine Attenuates Conventional Dialysis Fluid-Mediated Endothelial Cell Injury by Restoring Perturbed Cytoprotective Responses

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1678
Author(s):  
Rebecca Herzog ◽  
Maria Bartosova ◽  
Silvia Tarantino ◽  
Anja Wagner ◽  
Markus Unterwurzacher ◽  
...  

Long-term clinical outcome of peritoneal dialysis (PD) depends on adequate removal of small solutes and water. The peritoneal endothelium represents the key barrier and peritoneal transport dysfunction is associated with vascular changes. Alanyl-glutamine (AlaGln) has been shown to counteract PD-induced deteriorations but the effect on vascular changes has not yet been elucidated. Using multiplexed proteomic and bioinformatic analyses we investigated the molecular mechanisms of vascular pathology in-vitro (primary human umbilical vein endothelial cells, HUVEC) and ex-vivo (arterioles of patients undergoing PD) following exposure to PD-fluid. An overlap of 1813 proteins (40%) of over 3100 proteins was identified in both sample types. PD-fluid treatment significantly altered 378 in endothelial cells and 192 in arterioles. The HUVEC proteome resembles the arteriolar proteome with expected sample specific differences of mainly immune system processes only present in arterioles and extracellular region proteins primarily found in HUVEC. AlaGln-addition to PD-fluid revealed 359 differentially abundant proteins and restored the molecular process landscape altered by PD fluid. This study provides evidence on validity and inherent limitations of studying endothelial pathomechanisms in-vitro compared to vascular ex-vivo findings. AlaGln could reduce PD-associated vasculopathy by reducing endothelial cellular damage, restoring perturbed abundances of pathologically important proteins and enriching protective processes.

2002 ◽  
Vol 22 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Katarzyna Korybalska ◽  
Katarzyna Wieczorowska–Tobis ◽  
Alicja Polubinska ◽  
Justyna Wisniewska ◽  
James Moberly ◽  
...  

Objective L-2-Oxothiazolidine-4-carboxylate (OTZ), a cysteine precursor, is a substrate for intracellular glutathione synthesis. As shown previously, OTZ prevents free-radical induced cellular damage during in vitro simulation of peritoneal dialysis. In the present study, we examined the effect of adding OTZ to peritoneal dialysis solution on peritoneal function and structure during lipopolysaccharide (LPS)-induced peritonitis in rats. In addition, we studied the effects of pretreatment with OTZ (given orally) on the effects of LPS-induced peritonitis in rats. Methods Peritonitis was induced in rats by adding LPS (5 μg/mL) to the dialysis fluid. For acute experiments, rats were exposed to a single infusion of dialysis solution containing LPS or to LPS plus 5 mmol/L OTZ; peritoneal cell counts and permeability were determined after 4 hours. Alternatively, rats were pretreated with OTZ added to the drinking water (0.1%) for 10 days prior to infusion of LPS. For chronic experiments, peritoneal dialysis was performed over a 3-week period in rats with implanted peritoneal catheters. On days 8, 9, and 10 of the experiment, the rats were infused intraperitoneally with solution containing LPS (5 μg/mL), or LPS plus 5 mmol/L OTZ, to induce acute peritonitis. At the end of dialysis (10 days after the episodes of peritonitis), peritoneal function was assessed using a peritoneal equilibration test (PET), and peritoneal biopsies were taken to assess effects on peritoneal morphology. Results In the acute experiments, exposure to LPS led to increased peritoneal cell counts (+61% vs control, p < 0.05) and enhanced permeability of the peritoneum, leading to a loss in ultrafiltration (–63%, p < 0.0005). The glutathione concentration in peritoneal leukocytes also decreased during acute peritonitis (–31%, p < 0.05). During LPS-induced peritonitis, OTZ prevented the increase in dialysate cell count and the decrease in cellular glutathione content. Simultaneous administration of OTZ did not prevent the increased peritoneal permeability induced by LPS. However, in rats pretreated with OTZ, LPS-induced permeability to protein was significantly lower than in the nontreated animals (0.049 ± 0.011 vs 0.087 ± 0.034, p < 0.05). In the chronic experiments, LPS-induced peritonitis did not lead to any functional differences in peritoneal transport at the end of 3 weeks of dialysis. However, LPS-induced peritonitis led to increased thickness of the peritoneum and neovascularization within peritoneal interstitium compared to peritonitis-free animals. In contrast to the LPS-treated animals, the peritoneum of the rats exposed to LPS in the presence of OTZ was of a thickness similar to that in the control rats. Conclusion Supplementation of dialysis fluid with OTZ prevented changes in cellular glutathione levels and dialysate cell counts during acute peritonitis in rats. During chronic dialysis in rats exposed to intermittent peritonitis episodes, OTZ prevented increased thickening and neovascularization of the peritoneum. Our results suggest this may help to protect the peritoneal membrane during episodes of peritonitis.


2007 ◽  
Vol 51 (12) ◽  
pp. 4521-4524 ◽  
Author(s):  
Frances L. Clouse ◽  
Laurie B. Hovde ◽  
John C. Rotschafer

ABSTRACT This study compared the ability of telavancin to the ability of cefazolin and vancomycin to eliminate staphylococci from peritoneal dialysis fluid by using a static in vitro model to simulate the conditions of peritoneal dialysis. The results showed that telavancin exhibited statistically significantly better kill (P < 0.05) against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus.


2016 ◽  
Vol Volume 10 ◽  
pp. 3925-3932 ◽  
Author(s):  
Mario Bonomini ◽  
Sara Di Silvestre ◽  
Pamela Di Tomo ◽  
Natalia Di Pietro ◽  
Domitilla Mandatori ◽  
...  

1983 ◽  
Vol 3 (3) ◽  
pp. 128-129 ◽  
Author(s):  
Carol Loeppky ◽  
Eugene Tarka ◽  
E. Dale Everett

Often dialysis -associated peritonitis is treated before the results of cultures are known with a cephalosporin and an aminoglycoside in combination. Because there may be antagonism between the individual drugs in such combinations, we have investigated this possibility through the use of timed, killing curves in dialysate effluent. We tested various cephalosporins and aminoglycosides alone and in combination at concentrations usually instilled into the peritoneum and determined their activity against one strain each of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The results of these in-vitro studies show no evidence of antagonism but rather suggest an additive effect as evidenced by more rapid killing.


2003 ◽  
Vol 23 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Maria Cristina Ruiz ◽  
Manuel Portero–Otín ◽  
Reinald Pamplona ◽  
Jesús R. Requena ◽  
Joan Prat ◽  
...  

← Background Glucose degradation products (GDP) in dialysis fluids may induce nonenzymatic protein modifications, the chemical nature and biological properties of which should be better defined. ← Aims To characterize nonenzymatic protein modifications present in glucose-based peritoneal dialysis fluids (PDF) and to evaluate the relationship between concentrations of GDP and the derived nonenzymatic modifications, and the potential of PDF for generating these modifications in vitro. ← Methods The presence, distribution, and content of several nonenzymatic protein modifications in PDF were evaluated by immunological methods, by HPLC, and by gas chromatography-mass spectrometry (GC/MS). Peritoneal dialysis fluid-induced oxidative stress in cells was evaluated by flow cytometry. The potential of PDF for generating oxidative and glycoxidative modifications was examined by immunological and cross-linking analyses. ← Results The albumin present in PDF is modified by carboxymethyllysine (CML). GC/MS analyses of PDF proteins confirmed the presence of CML and demonstrated the occurrence of carboxyethyllysine, malondialdehyde lysine, and oxidation-derived semialdehydes. Furthermore, their concentrations in PDF proteins were significantly higher than those in plasma proteins (in all cases, p < 0.02). The concentration of pyrraline, a non-oxidative advanced glycation end-product, increased with dwell time up to 6 hours ( p < 0.03). The PDF induced cellular free-radical production, which was partially inhibited by the Maillard reaction inhibitor aminoguanidine ( p < 0.001). The potential to generate oxidative and glycoxidative modifications demonstrated an inverse relationship with dwell time ( p < 0.05). The PDF was able to induce collagen cross-linking in a close relationship with GDP concentration. ← Conclusions ( 1 ) PDF contains non-oxidative and several oxidative nonenzymatic protein modifications in higher concentrations than plasma. ( 2 ) Peritoneal dialysis fluid induces oxidative stress in vitro, which can be partially inhibited by aminoguanidine. ( 3 ) These properties are directly related to GDP concentration. ( 4 ) Peritoneal dialysis fluid is able to generate glycoxidative and oxidative damage to proteins in vitro in a dwell-time dependent fashion.


2016 ◽  
Vol 36 (4) ◽  
pp. 367-373 ◽  
Author(s):  
Sarah E. Herlihy ◽  
Hannah E. Starke ◽  
Melisa Lopez-Anton ◽  
Nehemiah Cox ◽  
Katayoon Keyhanian ◽  
...  

Long-term peritoneal dialysis (PD) often results in the development of peritoneal fibrosis. In many other fibrosing diseases, monocytes enter the fibrotic lesion and differentiate into fibroblast-like cells called fibrocytes. We find that peritoneal tissue from short-term PD patients contains few fibrocytes, while fibrocytes are readily observed in the peritoneal membrane of long-term PD patients. The PD fluid Dianeal (Baxter Healthcare Corporation, Deerfield, IL, USA) contains dextrose, a number of electrolytes including sodium chloride, and sodium lactate. We find that PD fluid potentiates human fibrocyte differentiation in vitro and implicates sodium lactate in this potentiation. The plasma protein serum amyloid P (SAP) inhibits fibrocyte differentiation. Peritoneal dialysis fluid and sodium chloride decrease the ability of human SAP to inhibit human fibrocyte differentiation in vitro. Together, these results suggest that PD fluid contributes to the development of peritoneal fibrosis by potentiating fibrocyte differentiation.


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