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indoxyl sulfate

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https://www.readbyqxmd.com/read/28314987/cooperative-inhibitory-effects-of-uremic-toxins-and-other-serum-components-on-oatp1b1-mediated-transport-of-sn-38
#1
Yurie Katsube, Masayuki Tsujimoto, Hiroyoshi Koide, Megumi Ochiai, Ayako Hojyo, Kaori Ogawa, Kengo Kambara, Nao Torii, Daisuke Shima, Taku Furukubo, Satoshi Izumi, Tomoyuki Yamakawa, Tetsuya Minegaki, Kohshi Nishiguchi
PURPOSE: Half-life of SN-38, an active metabolite of irinotecan, remarkably increases in patients with end-stage kidney disease (ESKD), even though SN-38 is excreted in bile. Uremic toxins (UTs), which accumulate in the serum of ESKD patients, were reported to inhibit organic anion-transporting polypeptide (OATP) 1B1-mediated uptake of SN-38; however, the relevance of this finding in a clinical setting is unknown. This study focused on cooperative effects of serum components and UTs on OATP1B1-mediated transport of SN-38...
March 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28314825/increased-plasma-exposures-of-conjugated-metabolites-of-morinidazole-in-renal-failure-patients-a-critical-role-of-uremic-toxins
#2
Fandi Kong, Xiaoyan Pang, Kan Zhong, Zitao Guo, Xiuli Li, Dafang Zhong, Xiaoyan Chen
Morinidazole is a 5-nitroimidazole drug. Its sulfate conjugate M7 was a sensitive substrate of organic anion transporter 1 (OAT1) and OAT3, whereas N+-glucuronides M8-1 and M8-2 were only OAT3 substrates. In chronic renal failure (CRF) patients, plasma exposures of the three conjugates increased by 15-fold, which were also found in 5/6 nephrectomized (5/6 Nx) rats in this study. Although the transcriptions of Oat1 and Oat3 in 5/6 Nx rat kidneys decreased by 50%, no difference was observed on the three conjugate uptakes between control and 5/6 Nx rat kidney slices...
March 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28277985/indoxyl-sulfate-potentiates-endothelial-dysfunction-via-reciprocal-role-for-reactive-oxygen-species-and-rhoa-rock-signaling-in-5-6-nephrectomized-rats
#3
Shuang Chu, Xiaodong Mao, Hengjiang Guo, Li Wang, Zezheng Li, Yang Zhang, Yunman Wang, Hao Wang, Xuemei Zhang, Wen Peng
Accumulative indoxyl sulfate (IS) retained in chronic kidney disease (CKD) can potentiate vascular endothelial dysfunction, and herein, we aim at elucidating the underlying mechanisms from the perspective of possible association between reactive oxygen species (ROS) and RhoA/ROCK pathway. IS-treated nephrectomized rats are administered with antioxidants including NADPH oxidase inhibitor apocynin, SOD analog tempol, and mitochondrion-targeted SOD mimetic mito-TEMPO to scavenge ROS, or ROCK inhibitor fasudil to obstruct RhoA/ROCK pathway...
March 13, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28264799/uremic-solute-indoxyl-sulfate-induced-platelet-hyperactivity-contributes-to-ckd-associated-thrombosis-in-mice
#4
Ke Yang, Changhong Du, Xinmiao Wang, Fengju Li, Yang Xu, Song Wang, Shilei Chen, Fang Chen, Mingqiang Shen, Mo Chen, Mengjia Hu, Ting He, Yongping Su, Junping Wang, Jinghong Zhao
Thrombosis is a common complication of chronic kidney disease (CKD), but the causes and mechanisms of CKD-associated thrombosis are not well clarified. Here, we show that platelet activity is remarkably enhanced in CKD mice, with increase of serum indoxyl sulfate (IS), a typical uremic toxin which cannot be effectively cleared by routine dialysis. Ex vivo and in vitro experiments reveal that IS displays a distinct ability to enhance platelet activities, including elevated response to collagen and thrombin, increases in platelet-derived microparticles and platelet-monocyte aggregates...
March 6, 2017: Blood
https://www.readbyqxmd.com/read/28202171/residual-renal-function-a-paradigm-shift
#5
Jerome Lowenstein, Jared J Grantham
Residual renal function (RRF) in patients undergoing dialysis treatments is currently viewed as glomerular filtrate that has escaped tubular reabsorption. RRF has been quantified as a clearance of urea or creatinine, or urea + creatinine. A major paradigm shift has followed the recognition that a substantial number of organic anion retention solutes (possible "uremic toxins") are protein-bound and therefore are not readily filtered. These protein-bound aryl compounds are secreted by renal tubular organic anion transporters (OATs)...
March 2017: Kidney International
https://www.readbyqxmd.com/read/28202164/manipulating-the-gut-microbiome-to-decrease-uremic-toxins
#6
Rabi Yacoub, Christina M Wyatt
The uremic solute indoxyl sulfate has been associated with increased mortality and other adverse outcomes in patients with chronic kidney disease. In a recent study published in Cell Host & Microbe, Devlin et al. describe a novel approach to alter the production of indoxyl sulfate through manipulation of the gut microbiota. Although this approach is far from clinical application, it may allow investigators to determine the contribution of uremic solutes to disease pathogenesis.
March 2017: Kidney International
https://www.readbyqxmd.com/read/28188231/diurnal-and-long-term-variation-in-plasma-concentrations-and-renal-clearances-of-circulating-markers-of-kidney-proximal-tubular-secretion
#7
Matthew B Rivara, Leila R Zelnick, Andrew N Hoofnagle, Rick Newitt, Russell P Tracy, Mario Kratz, David S Weigle, Bryan R Kestenbaum
BACKGROUND: The renal proximal tubule is essential for removing organic solutes and exogenous medications from the circulation. We evaluated diurnal, prandial, and long-term biological variation of 4 candidate endogenous markers of proximal tubular secretion. METHODS: We used LC-MS to measure plasma and urine concentrations of hippurate (HA), cinnamoylglycine (CMG), indoxyl sulfate (IS), and p-cresol sulfate (PCS) in 25 healthy adults. We measured plasma concentrations of secreted solutes at 13 time points over a 24-h period, and again after 2 weeks and 14 weeks of follow-up...
February 10, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28185988/effects-of-nonsteroidal-anti-inflammatory-drugs-on-the-renal-excretion-of-indoxyl-sulfate-a-nephro-cardiovascular-toxin-in-rats
#8
Chung-Ping Yu, Douglas H Sweet, Yu-Hsuan Peng, Yow-Wen Hsieh, Pei-Dawn Lee Chao, Yu-Chi Hou, Shiuan-Pey Lin
Chronic kidney disease (CKD) is a health problem worldwide. Indoxyl sulfate (IS) is a nephro-cardiovascular toxin accumulated in CKD patients and cannot be removed through hemodialysis. The renal excretion of IS was mediated by organic anion transporters (OATs) OAT 1 and OAT 3. Because a number of nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to inhibit OATs, we hypothesize that NSAIDs might inhibit the renal excretion of IS. Rats were intravenously injected IS with and without diclofenac, ketoprofen or salicylic acid, individually...
April 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28178126/free-and-total-p-cresol-sulfate-levels-and-infectious-hospitalizations-in-hemodialysis-patients-in-choice-and-hemo
#9
RANDOMIZED CONTROLLED TRIAL
Tanushree Banerjee, Timothy W Meyer, Tariq Shafi, Thomas H Hostetter, Michal Melamed, Yunnuo Zhu, Neil R Powe
The uremic syndrome is attributed to progressive retention of compounds that, under normal conditions, are excreted by the healthy kidneys. p-cresol sulfate (PCS), a prototype protein-bound uremic retention solute, has been shown to exert toxic effects in vitro. Recent studies have identified relations between increased levels of PCS and indoxyl sulfate (IS) and adverse clinical outcomes in hemodialysis patients. We explored the relationship between free and total PCS and IS with infection-related hospitalizations (IH) and septicemia in 2 cohorts, Choices for Healthy Outcomes in Caring for end-stage renal disease (ESRD) Study (CHOICE) and Hemodialysis Study (HEMO)...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28174171/indoxyl-sulfate-a-novel-cardiovascular-risk-factor-in-chronic-kidney-disease
#10
REVIEW
Szu-Chun Hung, Ko-Lin Kuo, Chih-Cheng Wu, Der-Cherng Tarng
No abstract text is available yet for this article.
February 7, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28122514/indoxyl-sulfate-the-uremic-toxin-linking-hemostatic-system-disturbances-with-the-prevalence-of-cardiovascular-disease-in-patients-with-chronic-kidney-disease
#11
Tomasz W Kamiński, Krystyna Pawlak, Małgorzata Karbowska, Michał Myśliwiec, Dariusz Pawlak
BACKGROUND: During chronic kidney disease progression, kidney-specific risk factors for cardiovascular disease come into play. The present study investigated the impact of indoxyl sulfate, dietary tryptophan-derived uremic toxin, accumulated in the blood of patients with chronic kidney disease on hemostatic parameters, markers of inflammation, oxidative stress and monocyte to macrophage transition. METHODS: Fifty-one CKD patients not undergoing hemodialysis were enrolled in the study...
January 25, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28107445/beta-glucans-supplementation-associates-with-reduction-in-p-cresyl-sulfate-levels-and-improved-endothelial-vascular-reactivity-in-healthy-individuals
#12
Carmela Cosola, Maria De Angelis, Maria Teresa Rocchetti, Eustacchio Montemurno, Valentina Maranzano, Giuseppe Dalfino, Carlo Manno, Annapaola Zito, Michele Gesualdo, Marco Matteo Ciccone, Marco Gobbetti, Loreto Gesualdo
BACKGROUND: Oat and barley beta-glucans are prebiotic fibers known for their cholesterol-lowering activity, but their action on the human gut microbiota metabolism is still under research. Although the induction of short-chain fatty acids (SCFA) following their ingestion has previously been reported, no study has investigated their effects on proteolytic uremic toxins p-cresyl sulfate (pCS) and indoxyl sulfate (IS) levels, while others have failed to demonstrate an effect on the endothelial function measured through flow-mediated dilation (FMD)...
2017: PloS One
https://www.readbyqxmd.com/read/28089366/limited-reduction-in-uremic-solute-concentrations-with-increased-dialysis-frequency-and-time-in-the-frequent-hemodialysis-network-daily-trial
#13
Tammy L Sirich, Kara Fong, Brett Larive, Gerald J Beck, Glenn M Chertow, Nathan W Levin, Alan S Kliger, Natalie S Plummer, Timothy W Meyer
The Frequent Hemodialysis Network Daily Trial compared conventional three-times weekly treatment to more frequent treatment with a longer weekly treatment time in patients receiving in-center hemodialysis. Evaluation at one year showed favorable effects of more intensive treatment on left ventricular mass, blood pressure, and phosphate control, but modest or no effects on physical or cognitive performance. The current study compared plasma concentrations of uremic solutes in stored samples from 53 trial patients who received three-times weekly in-center hemodialysis for an average weekly time of 10...
January 12, 2017: Kidney International
https://www.readbyqxmd.com/read/28067862/impact-of-indoxyl-sulfate-on-progenitor-cell-related-neovascularization-of-peripheral-arterial-disease-and-post-angioplasty-thrombosis-of-dialysis-vascular-access
#14
REVIEW
Chih-Cheng Wu, Szu-Chun Hung, Ko-Lin Kuo, Der-Cherng Tarng
Patients with chronic kidney disease (CKD) have an increased risk of vascular disease, which is associated with considerable health care costs. Vascular disease in CKD differs clinically and pathobiologically from that in patients with normal renal function. Besides the traditional risk factors, retention of uremic toxins contributes to the pathogenesis of vascular disease in patients with CKD. Indoxyl sulfate is a protein-bound uremic toxin and is inefficiently removed by conventional dialysis. Accumulating evidence suggests that indoxyl sulfate is a vascular toxin involved in atherosclerosis, arteriosclerosis, vascular calcification and vascular repair...
January 7, 2017: Toxins
https://www.readbyqxmd.com/read/28067806/high-uric-acid-ameliorates-indoxyl-sulfate-induced-endothelial-dysfunction-and-is-associated-with-lower-mortality-among-hemodialysis-patients
#15
Wei-Liang Hsu, Szu-Yuan Li, Jia-Sin Liu, Po-Hsun Huang, Shing-Jong Lin, Chih-Cheng Hsu, Yao-Ping Lin, Der-Cherng Tarng
High uric acid (UA) can act as a pro-oxidant in normal physiological conditions; however, emerging evidence is still debatable with regard to the association between high UA and poor outcomes among chronic hemodialysis (HD) patients. In the present study, 27,229 stable prevalent HD patients were enrolled and divided into four groups according to the quartiles of baseline UA concentration, and 5737 died during a median follow-up of 38 months. Multivariate Cox regression analysis showed that a UA level of <6...
January 6, 2017: Toxins
https://www.readbyqxmd.com/read/28025487/indoxyl-sulfate-as-a-mediator-involved-in-dysregulation-of-pulmonary-aquaporin-5-in-acute-lung-injury-caused-by-acute-kidney-injury
#16
Nozomi Yabuuchi, Masataka Sagata, Chika Saigo, Go Yoneda, Yuko Yamamoto, Yui Nomura, Kazuhiko Nishi, Rika Fujino, Hirofumi Jono, Hideyuki Saito
High mortality of acute kidney injury (AKI) is associated with acute lung injury (ALI), which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been elucidated. Here, we examined the involvement of a typical oxidative stress-inducing uremic toxin, indoxyl sulfate (IS), in the dysregulation of the pulmonary predominant water channel, aquaporin 5 (AQP-5), in bilateral nephrectomy (BNx)-induced AKI model rats...
December 23, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28006782/indoxyl-sulfate-impairs-endothelial-progenitor-cells-and-might-contribute-to-vascular-dysfunction-in-patients-with-chronic-kidney-disease
#17
Cheng-Jui Lin, Chih-Jen Wu, Pei-Chen Wu, Chi-Feng Pan, Tuan-Jen Wang, Fang-Ju Sun, Hsuan-Liang Liu, Han-Hsiang Chen, Hung-I Yeh
BACKGROUND/AIMS: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. METHODS: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed...
2016: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28001180/is-there-a-relationship-between-tryptophan-dietary-intake-and-plasma-levels-of-indoxyl-sulfate-in-chronic-kidney-disease-patients-on-hemodialysis
#18
Jessyca Sousa de Brito, Natália Alvarenga Borges, Carla Juliana Ribeiro Dolenga, José Carlos Carraro-Eduardo, Lia Sumie Nakao, Denise Mafra
INTRODUCTION: Gut microbiota is involved in generation of uremic toxins in chronic kidney disease (CKD) patients on hemodialysis (HD), like indoxyl sulfate (IS) that is originated from tryptophan amino acid fermentation. OBJECTIVE: To evaluate the tryptophan intake by chronic renal failure patients on HD and its possible relationship with IS plasma levels. METHODS: Participated of the study 46 patients with CKD on HD regular program (56.5% men; 52...
December 2016: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/27993865/simultaneous-determination-of-five-specific-and-sensitive-nephrotoxicity-biomarkers-in-serum-and-urine-samples-of-four-drug-induced-kidney-injury-models
#19
Liqiang Gu, Huiyan Shi, Ruowen Zhang, Zhe Wei, Kai-Shun Bi, Xiao-Hui Chen
In clinical diagnosis, serum creatinine (CR) was commonly used as the routine markers for the evaluation of kidney injury. To investigate the specific and sensitive nephrotoxicity biomarkers in different drug-induced kidney injury (DKI) models, receiver operating characteristic (ROC) analysis was applied in this study. The quantification data were acquired by the LC-MS determination. Histopathology results showed that different kinds of kidney injuries were observed in different DKI models (gentamycin, cisplatin, methotrexate and amphotericin B models), indicating the injuries might be caused by different mechanisms...
January 2017: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/27990791/the-role-of-carbon-adsorbent-in-the-conservative-management-of-chronic-kidney-disease
#20
Toshimitsu Niwa
Indoxyl sulfate is a uremic toxin, and cannot be removed efficiently by hemodialysis due to its protein-binding. Indoxyl sulfate induces cellular dysfunction by producing reactive oxygen species (ROS) such as superoxide by activating nicotinamide adenine dinucleotide phosphate oxidase, and by activating aryl hydrocarbon receptor through its uptake via organic anion transporters (OAT1 and OAT3). Indoxyl sulfate shows toxic effects on a variety of cells such as renal proximal tubular cells, glomerular mesangial cells, vascular smooth muscle cells, vascular endothelial cells, cardiomyocytes, cardiac fibroblasts, monocytes, osteoblasts, osteoclasts, and myocytes...
June 2017: Panminerva Medica
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