Identification of �-Aspartylglycine in Uremic Serum and Its Toxicity1

Author(s):  
Fumitake Gejyo ◽  
Yasutami Kinoshita ◽  
Giichi Ito ◽  
Tokuji Ikenaka
Keyword(s):  
RSC Advances ◽  
2020 ◽  
Vol 10 (71) ◽  
pp. 43489-43496
Author(s):  
Shaghayegh Saadati ◽  
Ubong Eduok ◽  
Amira Abdelrasoul ◽  
Ahmed Shoker

Rapid and highly sensitive quantitative analysis of 3-carboxy-4-methyl-5-propyl-2-furanpropionate and indole-3-acetic acid in uremic serum of patients with chronic kidney disease.


2018 ◽  
Vol 23 (2) ◽  
pp. 126-132 ◽  
Author(s):  
Hitoshi Uchiyama ◽  
Masayuki Tsujimoto ◽  
Akari Kimura ◽  
Eriko Yuki ◽  
Takashi Saiki ◽  
...  

2019 ◽  
Vol 44 (2) ◽  
pp. 277-285
Author(s):  
Patrycja Sosinska-Zawierucha ◽  
Beata Mackowiak ◽  
Andrzej Breborowicz

Background/Aims: Thromboembolic episodes are a frequent problem in end stage renal failure patients. The pathomechanism of the disorder is complex, including bioincompatibility of renal replacement therapy, endothelial dysfunction, increased blood level of procoagulant factors and uremic toxins. We studied changes in the functional properties of venous endothelial cells (VEC) in the presence of uremic serum and evaluated their possible modulation by N-acetylcysteine (NAC) or sulodexide (SUL). Methods: Serum samples from 12 uremic patients treated with hemodialysis were studied ex vivo on in vitro cultured VEC. In separate experiments, NAC 1 mmol/L or SUL 0.5 LRU/mL were added to uremic serum samples. Both changes in the gene expression and secretory activity of VEC were studied. Results: Uremic serum increased the expression of the following genes: IL6 +97%, p < 0.002; VEGF +28%, p < 0.002; vWF +47%, p < 0.002; PECAM +76%, p < 0.002; ICAM-1 +275%, p < 0.002; t-PA +96%, p < 0.002. Changes in gene expression were reflected by the increased secretory activity of VEC treated with the uremic serum. Exposure of VEC to uremic serum supplemented with NAC or SUL resulted in weaker stimulation of the studied genes’ expression. Also, secretion of the studied solutes, with the exception of ICAM-1, was reduced in the presence of NAC: IL6 –34%, p < 0.01; VEGF –40%, p < 0.005; vWF –25%, p < 0.001; t-PA –47%, p < 0.01, and MMP9 –37%, p < 0.001. SUL reduced the uremic serum-induced secretion of all solutes: IL6 –24%, p < 0.05; ICAM-1 –43%, p < 0.01; VEGF –38%, p < 0.01; vWF –23%, p < 0.01; t-PA –49%, p < 0.01, and MMP9 –25%, p < 0.05. Conclusions: Uremic serum induces prothrombotic changes in VEC, which may cause a predisposition to thrombotic disorders in patients with renal failure. NAC and SUL reduce the effects of the uremic serum in VEC, which suggests their potential therapeutic application in uremic patients.


2001 ◽  
Vol 86 (10) ◽  
pp. 1099-1105 ◽  
Author(s):  
Mireia Serradell ◽  
Aleix Cases ◽  
María Zurbano ◽  
José Aznar-Salatti ◽  
José López-Pedret ◽  
...  

SummaryWe have investigated the ability of serum from uremic patients to modify the thrombogenic properties of the endothelium. The effects of uremic medium on the morphology of endothelial cells (ECs), and their resistance to flow was analyzed. The influence of uremic media on the reactivity of the extracellular matrix (ECM) generated by ECs towards normal platelets was evaluated in a parallel-plate perfusion chamber. Exposure of ECs to uremic medium resulted in abnormal cell morphology and signs of an accelerated growth. Detachment of ECs exposed to circulating blood was increased when cells had been grown with media supplemented with uremic serum (21% vs. 14% non exposed). Platelet deposition was significantly elevated on ECMs generated in the presence of uremic media (uremicECMs) (p<0.01 vs. control studies). Effects of uremic serum were not observed at short incubation periods (5 h) but were evident after 24 or 72 h of incubation. Northern blot analysis revealed increased expression of tissue factor (TF) mRNA in ECs exposed to uremic conditions. Immunocytochemical methods detected an augmented expression of TF antigen on uremic ECMs. Incubation of ECMs with an antibody to human tissue factor prevented the increase in platelet deposition observed in uremic ECMs, suggesting that the presence of TF in ECM could be responsible for the enhanced platelet deposition. Results from our study indicate that uremic medium impairs the antithrombotic functions of cultured endothelial cells.


Author(s):  
Rafael Kramann ◽  
Simone K. Couson ◽  
Sabine Neuss ◽  
Uta Kunter ◽  
Manfred Bovi ◽  
...  

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 404 ◽  
Author(s):  
Rayana Maciel ◽  
Regiane Cunha ◽  
Valentina Busato ◽  
Célia Franco ◽  
Paulo Gregório ◽  
...  

Endothelial dysfunction in uremia can result in cell-to-cell junction loss and increased permeability, contributing to cardiovascular diseases (CVD) development. This study evaluated the impact of the uremic milieu on endothelial morphology and cell junction’s proteins. We evaluated (i) serum levels of inflammatory biomarkers in a cohort of chronic kidney disease (CKD) patients and the expression of VE-cadherin and Zonula Occludens-1 (ZO-1) junction proteins on endothelial cells (ECs) of arteries removed from CKD patients during renal transplant; (ii) ECs morphology in vitro under different uremic conditions, and (iii) the impact of uremic toxins p-cresyl sulfate (PCS), indoxyl sulfate (IS), and inorganic phosphate (Pi) as well as of total uremic serum on VE-cadherin and ZO-1 gene and protein expression in cultured ECs. We found that the uremic arteries had lost their intact and continuous endothelial morphology, with a reduction in VE-cadherin and ZO-1 expression. In cultured ECs, both VE-cadherin and ZO-1 protein expression decreased, mainly after exposure to Pi and uremic serum groups. VE-cadherin mRNA expression was reduced while ZO-1 was increased after exposure to PCS, IS, Pi, and uremic serum. Our findings show that uremia alters cell-to-cell junctions leading to an increased endothelial damage. This gives a new perspective regarding the pathophysiological role of uremia in intercellular junctions and opens new avenues to improve cardiovascular outcomes in CKD patients.


1987 ◽  
Vol 5 (1) ◽  
pp. 24-28 ◽  
Author(s):  
Jens Oluf Pedersen ◽  
Flemming Knudsen ◽  
Arne Høj Nielsen ◽  
Niels Grunnet

Nephron ◽  
2000 ◽  
Vol 85 (1) ◽  
pp. 60-64 ◽  
Author(s):  
Yasuhiro Tsutsumi ◽  
Toru Maruyama ◽  
Akira Takadate ◽  
Hidekata Shimada ◽  
Masaki Otagiri

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