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https://www.readbyqxmd.com/read/28420181/comment-on-indoxyl-sulfate-review-of-toxicity-and-therapeutic-strategies-toxins-2016-8-358
#1
Fellype C Barreto, Daniela V Barreto, Andrea E M Stinghen, Ziad A Massy
Recently, the clinical and experimental evidences that support the toxic effects of indoxyl sulfate, a protein-bound uremic toxin in chronic kidney disease (CKD) patients, has been discussed. In this panorama, the authors described several in vitro and in vivo studies, suggesting that indoxyl sulfate may play a part in the pathogenesis of low turnover bone disease. However, the discussion claims the need for relevant clinical studies in CKD patients whose bone turnover biomarkers and bone histomorphometry were assessed in order to demonstrate the association between serum levels of indoxyl sulfate and bone turnover...
April 17, 2017: Toxins
https://www.readbyqxmd.com/read/28411233/vasculopathy-in-the-setting-of-cardiorenal-syndrome-the-roles-of-protein-bound-uremic-toxins
#2
Jingbin Guo, Lu Lu, Yue Hua, Kevin Huang, Ian Wang, Li Huang, Qiang Fu, Aihua Chen, Paul Chan, Huimin Fan, Zhong-Min Liu, Bing Hui Wang
Chronic kidney disease (CKD) often leads to and accelerates the progression of cardiovascular disease (CVD), whilst CVD also causes kidney dysfunction. This bidirectional interaction leads to the development of a complex syndrome known as cardiorenal syndrome (CRS). CRS not only involves both the heart and the kidney, but also the vascular system through a vast array of contributing factors. In addition to hemodynamic, neuro-hormonal, mechanical and biochemical factors, the non-dialyzable protein-bound uremic toxins (PBUTs) are also key contributing factors that have been demonstrated through in vitro, in vivo and clinical observations...
April 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28405928/adynamic-bone-disease-is-a-predominant-bone-pattern-in-early-stages-of-chronic-kidney-disease
#3
REVIEW
Ziad Massy, Tilman Drueke
Chronic kidney disease (CKD) is complicated by disturbances of mineral and bone metabolism which start early in the course of the disease. It has long been assumed that high turnover bone lesions induced by secondary hyperparathyroidism are the predominant type of renal osteodystrophy from the start. However, there is increasing evidence in favor of the view that in early CKD stages low bone turnover is prevailing, with adynamic bone disease being the predominant form. Since serum parathyroid hormone levels increase progressively early on, and the most probable explanation is resistance to the skeletal action of this hormone...
April 12, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28396122/evaluation-of-the-impact-of-gut-microbiota-on-uremic-solute-accumulation-by-a-ce-tofms-based-metabolomics-approach
#4
Eikan Mishima, Shinji Fukuda, Chikahisa Mukawa, Akinori Yuri, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yasutoshi Akiyama, Noriko N Fukuda, Hiroki Tsukamoto, Kei Asaji, Hisato Shima, Koichi Kikuchi, Chitose Suzuki, Takehiro Suzuki, Yoshihisa Tomioka, Tomoyoshi Soga, Sadayoshi Ito, Takaaki Abe
Gut microbiota is involved in the metabolism of uremic solutes. However, the precise influence of microbiota to the retention of uremic solutes in CKD is obscure. To clarify this, we compared adenine-induced renal failure and control mice under germ-free or specific pathogen-free (SPF) conditions, examining the metabolite profiles of plasma, feces, and urine using a capillary electrophoresis time-of-flight mass spectrometry-based approach. Mice with renal failure under germ-free conditions demonstrated significant changes in plasma metabolites...
April 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28392999/sustained-uremic-toxin-control-improves-renal-and-cardiovascular-outcomes-in-patients-with-advanced-renal-dysfunction-post-hoc-analysis-of-the-kremezin-study-against-renal-disease-progression-in-korea
#5
Ran-Hui Cha, Shin Wook Kang, Cheol Whee Park, Dae Ryong Cha, Ki Young Na, Sung Gyun Kim, Sun Ae Yoon, Sejoong Kim, Sang Youb Han, Jung Hwan Park, Jae Hyun Chang, Chun Soo Lim, Yon Su Kim
BACKGROUND: We investigated the long-term effect of AST-120, which has been proposed as a therapeutic option against renal disease progression, in patients with advanced chronic kidney disease (CKD). METHODS: We performed post-hoc analysis with a per-protocol group of the K-STAR study (Kremezin study against renal disease progression in Korea) that randomized participants into an AST-120 and a control arm. Patients in the AST-120 arm were given 6 g of AST-120 in three divided doses, and those in both arms received standard conventional treatment...
March 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28379433/microbiome-perturbation-by-oral-vancomycin-reduces-plasma-concentration-of-two-gut-derived-uremic-solutes-indoxyl-sulfate-and-p-cresyl-sulfate-in-end-stage-renal-disease
#6
Lama Nazzal, Julia Roberts, Prabhjot Singh, Sachin Jhawar, Albert Matalon, Zhan Gao, Robert Holzman, Len Liebes, Martin J Blaser, Jerome Lowenstein
Background.: Observational studies have suggested a relationship between the plasma concentration of indoxyl sulfate (IS) and p -cresyl sulfate (PCS), small gut-derived 'uremic solutes', and the high incidence of uremic cardiomyopathy in patients with end-stage renal disease (ESRD). IS and PCS are derived from the metabolism of dietary components (tryptophan and tyrosine) by gut bacteria. This pilot study was designed to examine the effects of a poorly absorbable antibiotic (vancomycin) on the plasma concentration of two gut-derived 'uremic solutes', IS and PCS, and on the composition of the gut microbiome...
March 31, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28375181/dietary-metabolites-and-chronic-kidney-disease
#7
REVIEW
Sho Hasegawa, Tzu-Ming Jao, Reiko Inagi
Dietary contents and their metabolites are closely related to chronic kidney disease (CKD) progression. Advanced glycated end products (AGEs) are a type of uremic toxin produced by glycation. AGE accumulation is not only the result of elevated glucose levels or reduced renal clearance capacity, but it also promotes CKD progression. Indoxyl sulfate, another uremic toxin derived from amino acid metabolism, accumulates as CKD progresses and induces tubulointerstitial fibrosis and glomerular sclerosis. Specific types of amino acids (d-serine) or fatty acids (palmitate) are reported to be closely associated with CKD progression...
April 4, 2017: Nutrients
https://www.readbyqxmd.com/read/28341374/cardiorenal-disease-connection-during-post-menopause-the-protective-role-of-estrogen-in-uremic-toxins-induced-microvascular-dysfunction
#8
REVIEW
Jiayi Pei, Magdalena Harakalova, Hester den Ruijter, Gerard Pasterkamp, Dirk J Duncker, Marianne C Verhaar, Folkert W Asselbergs, Caroline Cheng
Female gender, post-menopause, chronic kidney disease (CKD) and (CKD linked) microvascular disease are important risk factors for developing heart failure with preserved ejection fraction (HFpEF). Enhancing our understanding of the interrelation between these risk factors could greatly benefit the identification of new drug targets for future therapy. This review discusses the evidence for the protective role of estradiol (E2) in CKD-associated microvascular disease and related HFpEF. Elevated circulating levels of uremic toxins (UTs) during CKD may act in synergy with hormonal changes during post-menopause and could lead to coronary microvascular endothelial dysfunction in HFpEF...
March 14, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28337716/long-term-variation-of-serum-levels-of-uremic-toxins-in-patients-treated-by-post-dilution-high-volume-on-line-hemodiafiltration-in-comparison-to-standard-low-flux-bicarbonate-dialysis-results-from-the-redert-study
#9
Vincenzo Panichi, Maria Teresa Rocchetti, Alessia Scatena, Alberto Rosati, Massimiliano Migliori, Francesco Pizzarelli, Loreto Gesualdo
PURPOSE OF THE STUDY: Little information have been provided till now regarding the effect of high volume HDF (hv-OL-HDF) in respect to standard bicarbonate dialysis (BHD) in medium-long term protein-bound toxins removal. PROCEDURES: A randomised cross-over multicentre study (REDERT study) was designed to compare the effects of hv-OL-HDF and low-flux BHD on uremic toxins serum levels in 36 chronic dialysis patients followed for 13 months. Group 1 patients were treated with BHD (Treatment A) for 6 months, and afterwards, they were transferred to hv-OL-HDF for a further 6 months (Treatment B)...
March 24, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28314987/cooperative-inhibitory-effects-of-uremic-toxins-and-other-serum-components-on-oatp1b1-mediated-transport-of-sn-38
#10
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...
April 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
April 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
#17
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
#18
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
#19
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
#20
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
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