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indoxyl sulfate

Jing Chen, Xiaoyan Zhang, Han Zhang, Tongqiang Liu, Hui Zhang, Jie Teng, Jun Ji, Xiaoqiang Ding
Chronic kidney disease (CKD) is a state of Klotho deficiency. The Klotho expression may be suppressed due to DNA hypermethylation in cancer cells so we have investigated the effects and possible mechanisms by which Klotho expression is regulated in human aortic smooth muscle cells (HASMCs). The vascular Klotho hypermethylation in radial arteries of patients with end-stage renal disease was described. Cultured HASMCs and 5/6-nephrectomized Sprague Dawley (SD) rats treated with indoxyl sulfate (IS) were used as in vitro and in vivo models, respectively...
2016: International Journal of Biological Sciences
Hua Chen, Gang Cao, Dan-Qian Chen, Ming Wang, Nosratola D Vaziri, Zhi-Hao Zhang, Jia-Rong Mao, Xu Bai, Ying-Yong Zhao
Early detection is critical in prevention and treatment of kidney disease. However currently clinical laboratory and histopathological tests do not provide region-specific and accurate biomarkers for early detection of kidney disease. The present study was conducted to identify sensitive biomarkers for early detection and progression of tubulo-interstitial nephropathy in aristolochic acid I-induced rats at weeks 4, 8 and 12. Biomarkers were validated using aristolochic acid nephropathy (AAN) rats at week 24, adenine-induced chronic kidney disease (CKD) rats and CKD patients...
September 28, 2016: Redox Biology
Denys Pavlenko, Esmée van Geffen, Mies J van Steenbergen, Griet Glorieux, Raymond Vanholder, Karin G F Gerritsen, Dimitrios Stamatialis
Hemodialysis is a widely available and well-established treatment for patients with End Stage Renal Disease (ESRD). However, although life-sustaining, patient mortality rates are very high. Several recent studies corroborated the link between dialysis patients' outcomes and elevated levels of protein-bound uremic toxins (PBUT) that are poorly removed by conventional hemodialysis. Therefore, new treatments are needed to improve their removal. Recently, our group showed that the combination of dialysis and adsorption on one membrane, the mixed matrix membrane (MMM), can effectively remove those toxins from human plasma...
October 5, 2016: Scientific Reports
Mami Kikuchi, Mariko Ueno, Yoshiharu Itoh, Wataru Suda, Masahira Hattori
BACKGROUND: In patients with chronic kidney disease (CKD), many metabolites of gut microbiota retain in the body as uremic toxins (UTs). However, the kinds of bacteria producing UTs are rarely discussed. METHODS: We analyzed UT production and the composition of gut microbiota in CKD rats and cecectomized rats. AST-120, a spherical carbon adsorbent, was administrated to evaluate how the precursors of UT affect gut microbiota. Serum and urine levels of UTs were quantified by liquid chromatography/electrospray ionization-tandem mass spectrometry...
October 5, 2016: Nephron
Akira Torigoe, Emiko Sato, Takefumi Mori, Norio Ieiri, Chika Takahashi, Yoko Ishida, Osamu Hotta, Sadayoshi Ito
Introduction Oxidative stress is one of the main mediators of progression of chronic kidney diseases (CKD). Nuclear factor E2-related factor 2 (Nrf2) is the transcription factor of antioxidant and detoxifying enzymes and related proteins which play an important role in cellular defense. Long-time hemodialysis (HD) therapy (8 hours) has been considered to be more beneficial compared to normal HD therapy (4 hours). We investigated oxidative response related to Nrf2 in peripheral blood mononuclear cells (PBMCs) of long-time HD and normal HD patients...
October 2016: Hemodialysis International
Janice Crespo-Salgado, V Matti Vehaskari, Tyrus Stewart, Michael Ferris, Qiang Zhang, Guangdi Wang, Eugene E Blanchard, Christopher M Taylor, Mahmoud Kallash, Larry A Greenbaum, Diego H Aviles
BACKGROUND: End-stage renal disease (ESRD) is associated with uremia and increased systemic inflammation. Alteration of the intestinal microbiota may facilitate translocation of endotoxins into the systemic circulation leading to inflammation. We hypothesized that children with ESRD have an altered intestinal microbiota and increased serum levels of bacterially derived uremic toxins. METHODS: Four groups of subjects were recruited: peritoneal dialysis (PD), hemodialysis (HD), post-kidney transplant and healthy controls...
2016: Microbiome
Lekha Tummalapalli, Girish N Nadkarni, Steven G Coca
PURPOSE OF REVIEW: Current biomarkers for chronic kidney disease (CKD) are limited by lack of sensitivity and inability to prognosticate CKD progression. Significant recent research has better characterized novel biomarker candidates that are associated with CKD progression and cardiovascular mortality in CKD. This review discusses the most significant advances within the past year. RECENT FINDINGS: We discuss biomarkers for outcomes in CKD under two categories: emerging (defined as having been validated in an independent cohort), which include serum cystatin C, serum β-trace protein, β2-microglobulin, soluble urokinase-type plasminogen activator receptor, soluble tumor necrosis factor receptors 1/2, urinary monocyte chemotactic protein-1, neutrophil gelatin-associated lipocalin, kidney injury molecule-1, and fibroblast growth factor-23; and novel (which have shown associations in smaller observational studies but have not been validated yet), which include indoxyl sulfate, p-cresyl sulfate, trimethylamine-N-oxide, IL-18, Klotho, markers of endothelial dysfunction, vimentin, and procollagen type III N-terminal propeptide...
November 2016: Current Opinion in Nephrology and Hypertension
Xiao Tan, Xuesen Cao, Jianzhou Zou, Bo Shen, Xiaoyan Zhang, Zhonghua Liu, Wenlv Lv, Jie Teng, Xiaoqiang Ding
Chronic kidney disease (CKD) is an increasingly recognized disease with high global incidence and mortality. Yet, the existing diagnostic tools are not sufficient enough to predict prognosis of CKD and CKD comorbidities. Indoxyl sulfate, a typical uremic toxin, is of great importance in the development of CKD with its nephrotoxicity, cardiovascular toxicity, and bone toxicity. Some reports suggest that indoxyl sulfate directly associate with renal function loss and mortality in CKD patients. This review discusses the diagnostic value of indoxyl sulfate from its biological characteristics, pathophysiological effects, related therapies, and its diagnostic value in clinical studies...
September 12, 2016: Hemodialysis International
Masaru Obokata, Hiroaki Sunaga, Hideki Ishida, Kyoko Ito, Tetsuya Ogawa, Yoshitaka Ando, Masahiko Kurabayashi, Kazuaki Negishi
UNLABELLED: End-stage renal disease is a major clinical and public health problem, and cardiovascular disease accounts for half of the mortality in hemodialysis patients. An existing mortality risk score (AROii score) or N-terminal pro-brain natriuretic peptide (NT-proBNP) level have modest predictive power, but there is room for improvement. There are emerging cardiac biomarkers (soluble isoforms of ST2 [sST2], galectin-3 [Gal-3]), and uremic toxicity (indoxyl sulfate). We sought to determine whether these biomarkers predict cardiovascular outcomes in hemodialysis patients and have incremental prognostic value over the clinical score and NT-proBNP level...
September 2016: American Heart Journal
Guangmang Liu, Xianjian Wu, Gang Jia, Xiaoling Chen, Hua Zhao, Jing Wang, Caimei Wu, Jingyi Cai
Arginine regulates growth performance, nutrient metabolism and health effects, but the underlying mechanism remains unknown. This study aims to investigate the effect of dietary arginine supplementation on rat growth performance and urinary metabolome through ¹H-NMR spectroscopy. Twenty rats were randomly assigned to two groups supplemented with 0% or 1.0% l-arginine for 4 weeks. Urine samples were analyzed through NMR-based metabolomics. Arginine supplementation significantly increased the urine levels of 4-aminohippurate, acetate, creatine, creatinine, ethanolamine, formate, hippurate, homogentisate, indoxyl sulfate, and phenylacetyglycine...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Sophie H Narath, Selma I Mautner, Eva Svehlikova, Bernd Schultes, Thomas R Pieber, Frank M Sinner, Edgar Gander, Gunnar Libiseller, Michael G Schimek, Harald Sourij, Christoph Magnes
Bariatric surgery is currently one of the most effective treatments for obesity and leads to significant weight reduction, improved cardiovascular risk factors and overall survival in treated patients. To date, most studies focused on short-term effects of bariatric surgery on the metabolic profile and found high variation in the individual responses to surgery. The aim of this study was to identify relevant metabolic changes not only shortly after bariatric surgery (Roux-en-Y gastric bypass) but also up to one year after the intervention by using untargeted metabolomics...
2016: PloS One
Yuanyuan Zhang, Liqiang Gu, Yu Jiang, Kaishun Bi, Xiaohui Chen
Fast and sensitive monitoring of drug-induced liver and kidney injury in early stage is beneficial. An ultrafast liquid chromatography with tandem mass spectrometry assay was developed and validated to simultaneously determine ten endogenous biomarkers in serum and urine, including hippuric acid, phenylacetylglycine, 5-oxoproline, cholic acid, taurine, indoleacetic acid, 3-indoxyl sulfate, guanidinosuccinic acid, guanidinoacetic acid and uric acid. A CAPCELL CORE PC column (2.1 × 150 mm, 2.7 μm) was adopted for analytes separation...
October 2016: Journal of Separation Science
Duyen Thi Do, Nam Nhut Phan, Chih-Yang Wang, Zhengda Sun, Yen-Chang Lin
Indoxyl sulfate (IS) is a digestive intermediate product that is a known indicator of chronic kidney disease. Its toxicity has also been suggested to accelerate chronic kidney disease. Recently, mesenchymal stem cells (MSCs) have been confirmed as a potential treatment in kidney regeneration. To determine the universal alteration in gene expression, we combined high-throughput microarray technology and in vitro culture of adipose-derived mesenchymal stem cells at different doses of IS (20, 40, 60 mg/l). We found that indoxyl sulfate has a remarkable interconnection with stem cell and calcium/calmodulin-dependent kinase pathways...
August 22, 2016: Cytotechnology
Yuki Enoki, Hiroshi Watanabe, Riho Arake, Ryusei Sugimoto, Tadashi Imafuku, Yuna Tominaga, Yu Ishima, Shunsuke Kotani, Makoto Nakajima, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
Skeletal muscle atrophy, referred to as sarcopenia, is often observed in chronic kidney disease (CKD) patients, especially in patients who are undergoing hemodialysis. The purpose of this study was to determine whether uremic toxins are involved in CKD-related skeletal muscle atrophy. Among six protein-bound uremic toxins, indole containing compounds, indoxyl sulfate (IS) significantly inhibited proliferation and myotube formation in C2C12 myoblast cells. IS increased the factors related to skeletal muscle breakdown, such as reactive oxygen species (ROS) and inflammatory cytokines (TNF-α, IL-6 and TGF-β1) in C2C12 cells...
2016: Scientific Reports
Guangmang Liu, Wei Cao, Tingting Fang, Gang Jia, Hua Zhao, Xiaoling Chen, Caimei Wu, Jing Wang
Glutamine and N-carbamylglutamate can enhance growth performance and health in animals, but the underlying mechanisms are not yet elucidated. This study aimed to investigate the effect of glutamine and N-carbamylglutamate supplementation in rat metabolism. Thirty rats were fed a control, glutamine, or N-carbamylglutamate diet for four weeks. Urine samples were analyzed by nuclear magnetic resonance (NMR)-based metabolomics, specifically high-resolution ¹H NMR metabolic profiling combined with multivariate data analysis...
2016: Nutrients
Troy D Hubbard, Iain A Murray, William H Bisson, Alexis P Sullivan, Aswathy Sebastian, George H Perry, Nina G Jablonski, Gary H Perdew
We have identified a fixed nonsynonymous sequence difference between humans (Val381; derived variant) and Neandertals (Ala381; ancestral variant) in the ligand-binding domain of the aryl hydrocarbon receptor (AHR) gene. In an exome sequence analysis of four Neandertal and Denisovan individuals compared with nine modern humans, there are only 90 total nucleotide sites genome-wide for which archaic hominins are fixed for the ancestral nonsynonymous variant and the modern humans are fixed for the derived variant...
October 2016: Molecular Biology and Evolution
Yuichi Ichimura, Hiroyuki Takamatsu, Hideki Ideuchi, Masako Oda, Kiyotaka Takeda, Hiroshi Saitoh
When the kidney is seriously impaired, various uremic toxins (UTs) accumulate in the body, often exerting unfavorable effects on physiological functions and drug pharmacokinetics. To prevent this, it is important to determine plasma UT levels accurately in chronic kidney disease patients. Although attempts to predict plasma UT levels using biomarkers have been made, the correlation between UT levels and the markers is not yet fully understood. In this study, we assessed the correlations among plasma levels of indoxyl sulfate (IS), indoleacetic acid (IA), and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) in 20 hemodialysis patients and evaluated the relationship between the plasma levels of UTs and clinical parameters, such as serum creatinine (Scr), blood urea nitrogen, and estimated glomerular filtration rate (eGFR), with special focus on IS...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Rangaraj Narayanan, Lisa Liu, Matthew Hoffmann, Sekhar Surapaneni
: Chronic kidney disease (CKD) generally impacts clearance of renally eliminated drugs but growing evidence shows that it can influence clearance of hepatically eliminated drugs and a complete mechanistic understanding of this phenomenon is still lacking. CKD leads to accumulation of uremic toxins, including indoxyl-3-sulfate (3-INDS) and indole-3-acetic acid (3-IAA). OBJECTIVE: In this study, we evaluated the potential of 3-INDS and 3-IAA (10, 30 and 100 μM) to induce liver cytochrome P450 (CYP) enzymes CYP1A2, 2B6 and 3A4/5 using cultured primary human hepatocytes following once daily treatment for 3 days...
July 19, 2016: Drug Metabolism Letters
Rangaraj Narayanan, Lisa Liu, Matthew Hoffmann, Sekhar Surapaneni
: Chronic kidney disease (CKD) generally impacts clearance of renally eliminated drugs but growing evidence shows that it can influence clearance of hepatically eliminated drugs and a complete mechanistic understanding of this phenomenon is still lacking. CKD leads to accumulation of uremic toxins, including indoxyl-3-sulfate (3-INDS) and indole-3-acetic acid (3-IAA). OBJECTIVE: In this study, we evaluated the potential of 3-INDS and 3-IAA (10, 30 and 100 μM) to induce liver cytochrome P450 (CYP) enzymes CYP1A2, 2B6 and 3A4/5 using cultured primary human hepatocytes following once daily treatment for 3 days...
July 19, 2016: Drug Metabolism Letters
Chang-Yun Yoon, Jimin Park, Changhwan Seo, Bo Young Nam, Seonghun Kim, Youn Kyung Kee, Misol Lee, Min-Uk Cha, Hyoungnae Kim, Seohyun Park, Hae-Ryong Yun, Su-Young Jung, Jong Hyun Jhee, Young Eun Kwon, Meiyan Wu, Jae Eun Um, Hye-Young Kang, Jung Tak Park, Seung Hyeok Han, Shin-Wook Kang, Hyeon Chang Kim, Sungha Park, Sung-Kil Lim, Tae-Hyun Yoo
OBJECTIVE: Recent reports demonstrated that dentin matrix protein 1 (DMP1) acts as an inhibitor of vascular calcification and might be a potential biomarker for chronic kidney disease-mineral and bone disorder; however, no clinical investigations regarding DMP1 have been performed in dialysis patients. We investigated the prognostic value of DMP1 on cardiovascular outcomes in prevalent peritoneal dialysis patients. DESIGN AND METHOD: We recruited 223 prevalent peritoneal dialysis patients and divided them into high and low DMP1 groups according to log transformed plasma DMP1 levels...
July 8, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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