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https://www.readbyqxmd.com/read/28811853/effects-of-sevelamer-hydrochloride-on-uremic-toxins-serum-indoxyl-sulfate-and-p-cresyl-sulfate-in-hemodialysis-patients
#1
Cheng-Jui Lin, Chi-Feng Pan, Chih-Kuang Chuang, Hsuan-Liang Liu, Sung-Fa Huang, Han-Hsiang Chen, Chih-Jen Wu
BACKGROUND: Beside the phosphate binding effect, non-calcium non-aluminum phosphate binder, namely sevelamer hydrochloride (SH), has many other effects in dialysis patients. It can absorb many other compounds, decrease low-density lipoprotein cholesterol (LDL-C) level, and attenuate the progression of vascular calcification; it has been reported to have anti-inflammatory effect. However, it is not clear whether it has any effect on uremic toxins, i.e. serum indoxyl sulfate (IS) and p-cresyl sulfate, (PCS) in hemodialysis (HD) patients...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28781957/indoxyl-sulfate-a-uremic-toxin-in-chronic-kidney-disease-suppresses-both-bone-formation-and-bone-resorption
#2
Kenta Watanabe, Tsukasa Tominari, Michiko Hirata, Chiho Matsumoto, Junya Hirata, Gillian Murphy, Hideaki Nagase, Chisato Miyaura, Masaki Inada
Abnormalities of bone turnover are commonly observed in patients with chronic kidney disease (CKD), and the low-turnover bone disease is considered to be associated with low serum parathyroid hormone (PTH) levels and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood of patients with CKD. Recently, we have reported that IS exacerbates low bone turnover induced by parathyroidectomy (PTX) in adult rats, and suggested that IS directly induces low bone turnover through the inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28754616/role-of-uremic-toxin-indoxyl-sulfate-in-the-progression-of-cardiovascular-disease
#3
REVIEW
Huichang Gao, Shan Liu
The prevalence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) is relatively high. Deterioration of renal function in CKD leads to accumulation of indoxyl sulfate, a tryptophan metabolite produced by gut microbiota. It is acknowledged that indoxyl sulfate is capable to stimulate oxidative stress, which in turn contributes to the progression of vascular disorders and its resultant coronary artery disease. Recent research have demonstrated the adverse effects of indoxyl sulfate on the heart, together with the acceleration of vascular dysfunction, suggesting that indoxyl sulfate might contribute to high prevalence of CVD in CKD...
July 25, 2017: Life Sciences
https://www.readbyqxmd.com/read/28753957/the-uremic-toxin-indoxyl-sulfate-accelerates-thrombotic-response-after-vascular-injury-in-animal-models
#4
Malgorzata Karbowska, Tomasz W Kaminski, Natalia Marcinczyk, Tomasz Misztal, Tomasz Rusak, Lukasz Smyk, Dariusz Pawlak
Chronic kidney disease (CKD) patients are at high risk for thrombotic events. Indoxyl sulfate (IS) is one of the most potent uremic toxins that accumulates during CKD. Even though IS is associated with an increased risk for cardiovascular disease, its impact on thrombotic events still remains not fully understood. The purpose of the study was to evaluate the direct effect of IS on thrombotic process. We examined the impact of acute exposure to IS on thrombus development induced by electric current in Wistar rats, intravital thrombus formation after laser-induced injury in the mice endothelium, coagulation profile, clot formation dynamics, platelet aggregations, and erythrocyte osmotic resistance...
July 19, 2017: Toxins
https://www.readbyqxmd.com/read/28747155/indole-3-acetic-acid-indoxyl-sulfate-and-paracresyl-sulfate-do-not-influence-anemia-parameters-in-hemodialysis-patients
#5
Stanislas Bataille, Marion Pelletier, Marion Sallée, Yvon Berland, Nathalie McKay, Ariane Duval, Stéphanie Gentile, Yosra Mouelhi, Philippe Brunet, Stéphane Burtey
BACKGROUND: The main reason for anemia in renal failure patients is the insufficient erythropoietin production by the kidneys. Beside erythropoietin deficiency, in vitro studies have incriminated uremic toxins in the pathophysiology of anemia but clinical data are sparse. In order to assess if indole 3-acetic acid (IAA), indoxyl sulfate (IS), and paracresyl sulfate (PCS) -three protein bound uremic toxins- are clinically implicated in end-stage renal disease anemia we studied the correlation between IAA, IS and PCS plasmatic concentrations with hemoglobin and Erythropoietin Stimulating Agents (ESA) use in hemodialysis patients...
July 26, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28739139/results-of-the-hemo-study-suggest-that-p-cresol-sulfate-and-indoxyl-sulfate-are-not-associated-with-cardiovascular-outcomes
#6
Tariq Shafi, Tammy L Sirich, Timothy W Meyer, Thomas H Hostetter, Natalie S Plummer, Seungyoung Hwang, Michal L Melamed, Tanushree Banerjee, Josef Coresh, Neil R Powe
Cardiovascular disease, the leading cause of mortality in hemodialysis patients, is not fully explained by traditional risk factors. To help define non-traditional risk factors, we determined the association of predialysis total p-cresol sulfate, indoxyl sulfate, phenylacetylglutamine, and hippurate with cardiac death, sudden cardiac death, and first cardiovascular event in the 1,273 participants of the HEMO Study. The results were adjusted for potential demographic, clinical, and laboratory confounders. The mean age of the patients was 58 years, 63% were Black and 42% were male...
July 21, 2017: Kidney International
https://www.readbyqxmd.com/read/28727768/benign-and-tumor-parenchyma-metabolomic-profiles-affect-compensatory-renal-growth-in-renal-cell-carcinoma-surgical-patients
#7
Barak Rosenzweig, Nimrod D Rubinstein, Ed Reznik, Roman Shingarev, Krishna Juluru, Oguz Akin, James J Hsieh, Edgar A Jaimes, Paul Russo, Katalin Susztak, Jonathan A Coleman, A Ari Hakimi
BACKGROUND AND OBJECTIVES: Pre-operative kidney volume is an independent predictor of glomerular filtration rate in renal cell carcinoma patients. Compensatory renal growth (CRG) can ensue prior to nephrectomy in parallel to tumor growth and benign parenchyma loss. We aimed to test whether renal metabolite abundances significantly associate with CRG, suggesting a causative relationship. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Tissue metabolomics data from 49 patients, with a median age of 60 years, were previously collected and the pre-operative fold-change of their contra to ipsi-lateral benign kidney volume served as a surrogate for their CRG...
2017: PloS One
https://www.readbyqxmd.com/read/28706886/the-effects-of-indoxyl-sulfate-induced-endothelial-microparticles-on-neointimal-hyperplasia-formation-in-an-ex-vivo-model
#8
Jung-Hwa Ryu, HeeJung Park, Seung-Jung Kim
PURPOSE: Neointimal hyperplasia (NH) is considered to be one of the main causes of vascular access occlusion in patients receiving hemodialysis. Endothelial injury and TGF-β-mediated proliferation of vascular smooth muscle cells (VSMCs) induce NH. Endothelial microparticles (EMPs) are also increased by endothelial injury. We aimed to investigate the effects of EMPs and TGF-β expression on VSMC proliferation and their contributions to NH formation in an ex vivo model. METHODS: EMPs were collected from the culture media of human umbilical vein endothelial cells treated with indoxyl sulfate (IS, 250 µg/mL) after ultracentrifugation at 100,000 × g...
July 2017: Annals of Surgical Treatment and Research
https://www.readbyqxmd.com/read/28696247/microrna-92a-mediates-endothelial-dysfunction-in-ckd
#9
Fenqing Shang, Shen-Chih Wang, Chien-Yi Hsu, Yifei Miao, Marcy Martin, Yanjun Yin, Chih-Cheng Wu, Yun-Ting Wang, Gaihong Wu, Shu Chien, Hsien-Da Huang, Der-Cherng Tarng, Yan-Ting Shiu, Alfred K Cheung, Po-Hsun Huang, Zhen Chen, John Y-J Shyy
CKD is an independent risk factor for cardiovascular disease (CVD). The accumulation of uremic toxins in CKD induces oxidative stress and endothelial dysfunction. MicroRNA-92a (miR-92a) is induced by oxidative stress in endothelial cells (ECs) and involved in angiogenesis and atherosclerosis. We investigated a role for oxidative stress-responsive miR-92a in CKD. Our study of patients at three clinical sites showed increased serum miR-92a level with decreased kidney function. In cultured ECs, human CKD serum or uremic toxins (such as indoxyl sulfate), compared with non-CKD serum, induced the levels of miR-92a and suppressed the expression of miR-92a targets, including key endothelial-protective molecules...
July 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28694431/key-role-for-the-organic-anion-transporters-oat1-and-oat3-in-the-in-vivo-handling-of-uremic-toxins-and-solutes
#10
Wei Wu, Kevin T Bush, Sanjay K Nigam
In vitro data indicates that the kidney proximal tubule (PT) transporters of uremic toxins and solutes (e.g., indoxyl sulfate, p-cresol sulfate, kynurenine, creatinine, urate) include two "drug" transporters of the organic anion transporter (OAT) family: OAT1 (SLC22A6, originally NKT) and OAT3 (SLC22A8). Here, we have examined new and prior metabolomics data from the Oat1KO and Oat3KO, as well as newly obtained metabolomics data from a "chemical double" knockout (Oat3KO plus probenecid). This gives a picture of the in vivo roles of OAT1 and OAT3 in the regulation of the uremic solutes and supports the centrality of these "drug" transporters in independently and synergistically regulating uremic metabolism...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28659803/indoxyl-sulfate-affects-glial-function-increasing-oxidative-stress-and-neuroinflammation-in-chronic-kidney-disease-interaction-between-astrocytes-and-microglia
#11
Simona Adesso, Tim Magnus, Salvatore Cuzzocrea, Michela Campolo, Björn Rissiek, Orlando Paciello, Giuseppina Autore, Aldo Pinto, Stefania Marzocco
Indoxyl sulfate (IS) is a protein-bound uremic toxin resulting from the metabolism of dietary tryptophan which accumulates in patients with impaired renal function, such as chronic kidney disease (CKD). IS is a well-known nephrovascular toxin but little is known about its effects on central nervous system (CNS) cells. Considering the growing interest in the field of CNS comorbidities in CKD, we studied the effect of IS on CNS cells. IS (15-60 μM) treatment in C6 astrocyte cells increased reactive oxygen species release and decreased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation, and heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 expression...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28654798/the-impact-of-gut-microbiota-on-kidney-function-and-pathogenesis
#12
REVIEW
Fariba Mahmoodpoor, Yalda Rahbar Saadat, Abolfazl Barzegari, Mohammadreza Ardalan, Sepideh Zununi Vahed
Chronic kidney diseases (CKDs) are a global health problem. Besides diverse leading reasons in initiation and progression of CKDs, it is evident that they might largely originate from changes in the gut microbial community (microbiota). Mounting evidence indicates that a bidirectional relationship exists between host and microbiome in humans and animals with CKDs. Changes in the microbiota composition and structure (dysbiosis) produce excessive amounts of uremic toxins (e.g. indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide) but less reno-protective metabolites that are implicated in oxidative stress, uremia, inflammation, deterioration of kidney function, kidney diseases progression, a higher prevalence of cardiovascular risk, and mortality in patients with CKD...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28608457/potential-therapeutic-interventions-for-chronic-kidney-disease-associated-sarcopenia-via-indoxyl-sulfate-induced-mitochondrial-dysfunction
#13
Yuki Enoki, Hiroshi Watanabe, Riho Arake, Rui Fujimura, Kana Ishiodori, Tadashi Imafuku, Kento Nishida, Ryusei Sugimoto, Saori Nagao, Shigeyuki Miyamura, Yu Ishima, Motoko Tanaka, Kazutaka Matsushita, Hirotaka Komaba, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
BACKGROUND: Chronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS-targeted intervention using AST-120, which inhibits IS accumulation, or mitochondria-targeted intervention using L-carnitine or teneligliptin, a dipeptidyl peptidase-4 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice...
June 12, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28605162/targeted-metabolomics-analysis-of-aromatic-amino-acids-and-their-gut-microbiota-host-co-metabolites-in-rat-serum-and-urine-by-liquid-chromatography-with-tandem-mass-spectrometry
#14
Yifeng Zeng, Liang Luo, Waner Hou, Biyu Lu, Jing Gong, Jiahui Chen, Xiaojun Zhang, Bo Han, Zhiyong Xie, Qiongfeng Liao
Gut microbiota-host co-metabolites are closely related to various diseases. Monitoring dynamic changes of co-metabolites can provide a more comprehensive understanding of pathophysiology. Here, a novel liquid chromatography-tandem mass spectrometry method was performed for the analysis of aromatic amino acids and their gut microbiota-host co-metabolites in rat serum and urine. In the developed method, seven key gut microbiota-host co-metabolites were chromatographically separated on a Kinetex Phenyl-Hexyl column by gradient elution, and the run time was 6 min...
June 12, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28596556/indoxyl-sulfate-is-mediated-immune-dysfunction-provokes-endothelial-damage-in-patients-with-end-stage-renal-disease-esrd
#15
Hee Young Kim, Tae-Hyun Yoo, Yuri Hwang, Ga Hye Lee, Bonah Kim, Jiyeon Jang, Hee Tae Yu, Min Chang Kim, Joo-Youn Cho, Chan Joo Lee, Hyeon Chang Kim, Sungha Park, Won-Woo Lee
Progressive renal failure causes uremia-related immune dysfunction, which features a chronic inflammatory milieu. Given the central role of end-stage renal disease (ESRD)-related immune dysfunction in the pathogenesis of cardiovascular diseases (CVDs), much attention has been focused on how uremic toxins affect cellular immunity and the mechanisms underlying pathogenesis of atherosclerosis in ESRD patients. Here, we investigated the characteristics of monocytes and CD4(+) T cells in ESRD patients and the immune responses induced by indoxyl sulfate (IS), a key uremic toxin, in order to explore the pathogenic effects of these cells on vascular endothelial cells...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28589039/gum-arabic-reduces-c-reactive-protein-in-chronic-kidney-disease-patients-without-affecting-urea-or-indoxyl-sulfate-levels
#16
Sarra Elamin, Mariam J Alkhawaja, Amina Y Bukhamsin, Mohamed A S Idris, Muntasir M Abdelrahman, Nasrulla K Abutaleb, Abdulrahman A Housawi
INTRODUCTION: Gum Arabic (GA) is a complex polysaccharide with proven prebiotic properties and potentially beneficial systemic effects. METHODS: We randomly allocated 36 chronic kidney disease (CKD) patients to receive 10, 20, or 40 grams daily of GA for four weeks and studied the systemic effects of this intervention. RESULTS: Thirty participants completed the study with baseline glomerular filtration rate 29.1 ± 9.9 mL/min/1.7 m(2)...
2017: International Journal of Nephrology
https://www.readbyqxmd.com/read/28582807/dietary-fiber-intake-is-associated-with-chronic-kidney-disease-ckd-progression-and-cardiovascular-risk-but-not-protein-nutritional-status-in-adults-with-ckd
#17
Lu Lu, Yan-Feng Huang, Ming-Qing Wang, De-Xiu Chen, Heng Wan, Lian-Bo Wei, Wei Xiao
BACKGROUND AND OBJECTIVES: Evidence suggests that dietary fiber benefits patients with chronic kidney disease (CKD); however, this conclusion requires further validation. In this study, we examined the effects of dietary fiber on kidney function, inflammation, indoxyl sulfate, nutritional status, and cardiovascular risk in patients with advanced CKD. METHODS AND STUDY DESIGN: We performed linear regressions to assess the association between dietary fiber intake and CKD parameters...
2017: Asia Pacific Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28573386/uremic-toxicity-and-bone-in-ckd
#18
REVIEW
Suguru Yamamoto, Masafumi Fukagawa
Patients with chronic kidney disease (CKD), especially those on dialysis treatment, are at high risk of bone fracture. In CKD-mineral and bone disorder (CKD-MBD), secondary hyperparathyroidism in patients with advanced CKD induces bone abnormalities, and skeletal resistance to parathyroid hormone (PTH) starts in the early stages of kidney disease. Uremic toxins such as indoxyl sulfate and p-cresyl sulfate reduce the expression of PTH receptor as well as PTH-induced cyclic adenosine 3',5' monophosphate production in osteoblasts...
June 1, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28528271/exploring-binding-characteristics-and-the-related-competition-of-different-protein-bound-uremic-toxins
#19
Olivier Deltombe, Henriette de Loor, Griet Glorieux, Annemieke Dhondt, Wim Van Biesen, Björn Meijers, Sunny Eloot
Little is known about potential differences in binding characteristics of protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD) versus healthy controls. The question arises whether eventual differences are attributed to (i) the elevated levels of competing uremic toxins, and/or (ii) post-translational modifications of albumin. We evaluated the binding characteristics of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (pCS) by deriving a binding curve in three distinct conditions: (i) serum from healthy controls (healthy serum), (ii) blank serum from hemodialysis patients (blank HD serum; i...
May 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28508124/dna-hypermethylation-of-sfrp5-contributes-to-indoxyl-sulfate-induced-renal-fibrosis
#20
Yanlin Yu, Xu Guan, Ling Nie, Yong Liu, Ting He, Jiachuan Xiong, Xinli Xu, Yan Li, Ke Yang, Yiqin Wang, Yunjian Huang, Bing Feng, Jingbo Zhang, Jinghong Zhao
Renal fibrosis is the most common outcome of chronic kidney disease (CKD), while the pathogenesis of renal fibrosis is not fully understood. In this study, we first showed that the progress of renal fibrosis was positively related to serum levels of indoxyl sulfate, a typical protein-bound toxin, and that there was a close correlation between serum indoxyl sulfate levels and β-catenin expression in the kidneys (r = 0.908, p < 0.001) of CKD patients. We then demonstrated that intraperitoneal injections of indoxyl sulfate (100 mg/kg/day) for 4 weeks in uninephrectomized mice explicitly induced renal fibrosis, which was accompanied by a significant activation of Wnt/β-catenin signaling...
May 15, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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