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https://www.readbyqxmd.com/read/29592876/third-party-fecal-microbiota-transplantation-following-allo-hct-reconstitutes-microbiome-diversity
#1
Zachariah DeFilipp, Jonathan U Peled, Shuli Li, Jasmin Mahabamunuge, Zeina Dagher, Ann E Slingerland, Candice Del Rio, Betsy Valles, Maria E Kempner, Melissa Smith, Jami Brown, Bimalangshu R Dey, Areej El-Jawahri, Steven L McAfee, Thomas R Spitzer, Karen K Ballen, Anthony D Sung, Tara E Dalton, Julia A Messina, Katja Dettmer, Gerhard Liebisch, Peter Oefner, Ying Taur, Eric G Pamer, Ernst Holler, Michael K Mansour, Marcel R M van den Brink, Elizabeth Hohmann, Robert R Jenq, Yi-Bin Chen
We hypothesized that third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT). In this open-label single-group pilot study, 18 subjects were enrolled before allo-HCT and planned to receive third-party FMT capsules. FMT capsules were administered no later than 4 weeks after neutrophil engraftment, and antibiotics were not allowed within 48 hours before FMT. Five patients did not receive FMT because of the development of early acute gastrointestinal (GI) graft-versus-host disease (GVHD) before FMT (n = 3), persistent HCT-associated GI toxicity (n = 1), or patient decision (n = 1)...
April 10, 2018: Blood Advances
https://www.readbyqxmd.com/read/29550811/gum-acacia-improves-renal-function-and-ameliorates-systemic-inflammation-oxidative-and-nitrosative-stress-in-streptozotocin-induced-diabetes-in-rats-with-adenine-induced-chronic-kidney-disease
#2
Mohammed Al Za'abi, Suhail Al Salam, Yousuf Al Suleimani, Priyadarsini Manoj, Abderrahim Nemmar, Badreldin H Ali
BACKGROUND/AIMS: The effect of treatment with gum acacia (GA), a prebiotic shown previously to ameliorate chronic kidney disease (CKD), in diabetic and non - diabetic rats with adenine - induced CKD has been investigated using several conventional and novel physiological, biochemical, and histopathological parameters. METHODS: Diabetes mellitus was induced in rats by a single injection of streptozotocin (STZ). Diabetic and non - diabetic rats were randomly divided into several groups, and given either normal food or food mixed with adenine (0...
March 13, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29543732/indoxyl-sulfate-promotes-macrophage-il-1%C3%AE-production-by-activating-aryl-hydrocarbon-receptor-nf-%C3%AE%C2%BA-mapk-cascades-but-the-nlrp3-inflammasome-was-not-activated
#3
Takuya Wakamatsu, Suguru Yamamoto, Toru Ito, Yoko Sato, Koji Matsuo, Yoshimitsu Takahashi, Yoshikatsu Kaneko, Shin Goto, Junichiro James Kazama, Fumitake Gejyo, Ichiei Narita
In chronic kidney disease (CKD) patients, accumulation of uremic toxins is associated with cardiovascular risk and mortality. One of the hallmarks of kidney disease-related cardiovascular disease is intravascular macrophage inflammation, but the mechanism of the reaction with these toxins is not completely understood. Macrophages differentiated from THP-1 cells were exposed to indoxyl sulfate (IS), a representative uremic toxin, and changes in inflammatory cytokine production and intracellular signaling molecules including interleukin (IL)-1, aryl hydrocarbon receptor (AhR), nuclear factor (NF)-κ, and mitogen-activated protein kinase (MAPK) cascades as well as the NLRP3 inflammasome were quantified by real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay...
March 15, 2018: Toxins
https://www.readbyqxmd.com/read/29537310/generation-clearance-toxicity-and-monitoring-possibilities-of-unaccounted-uremic-toxins-for-improved-dialysis-prescriptions
#4
James Gilbert Atherton, David S Hains, John J Bissler, Bradford D Pendley, Erno Lindner
Current dialysis dosing calculations provide an incomplete assessment of blood purification. They do not include clearances of protein-bound uremic toxins like polyamines, p-cresol sulfate, and indoxyl sulfate, relying solely on the clearance of urea as a surrogate for all molecules accumulating in patients with end stage renal disease (ESRD). Protein-bound uremic toxins clear differently in dialysis but also during normal renal function. The kidney clears protein bound toxins via the process of secretion, while it clears urea through filtration...
March 14, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29511436/dihydroartemisinin-inhibits-indoxyl-sulfate-is-promoted-cell-cycle-progression-in-mesangial-cells-by-targeting-cox-2-mpges-1-pge-2-cascade
#5
Harr-Keshauve Mungun, Shuzhen Li, Yue Zhang, Songming Huang, Zhanjun Jia, Guixia Ding, Aihua Zhang
Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin and has been used as an antimalarial drug. Recently, roles of artemisinin and its derivatives in treating diseases besides antimalarial effect were documented. Thus, this study was undertaken to investigate the role of DHA in indoxyl sulfate (IS)-promoted cell cycle progression in glomerular mesangial cells, as well as the potential mechanisms. Under the basal condition, DHA significantly retarded the cell cycle progression as shown by decreased cell percentage in S phase and increased cell percentage in G1/G0 phases in line with reduced cell cycle proteins cyclin A2 and cyclin D1...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29474405/phenyl-sulfate-indoxyl-sulfate-and-p-cresyl-sulfate-decrease-glutathione-level-to-render-cells-vulnerable-to-oxidative-stress-in-renal-tubular-cells
#6
Takeo Edamatsu, Ayako Fujieda, Yoshiharu Itoh
In chronic kidney disease patients, oxidative stress is generally associated with disease progression and pathogenesis of its comorbidities. Phenyl sulfate is a protein-bound uremic solute, which accumulates in chronic kidney disease patients, but little is known about its nature. Although many reports revealed that protein-bound uremic solutes induce reactive oxygen species production, the effects of these solutes on anti-oxidant level have not been well studied. Therefore, we examined the effects of protein-bound uremic solutes on glutathione levels...
2018: PloS One
https://www.readbyqxmd.com/read/29470534/the-effect-of-isohydric-hemodialysis-on-the-binding-and-removal-of-uremic-retention-solutes
#7
Aleksey Etinger, Kumar, William Ackley, Leland Soiefer, Jonathan Chun, Prabjhot Singh, Eric Grossman, Albert Matalon, Robert S Holzman, Bjorn Meijers, Jerome Lowenstein
BACKGROUND: There is growing evidence that the accumulation of protein- bound uremic retention solutes, such as indoxyl sulfate, p-cresyl sulfate and kynurenic acid, play a role in the accelerated cardiovascular disease seen in patients undergoing chronic hemodialysis. Protein-binding, presumably to albumin, renders these solutes poor-dialyzable. We previously observed that the free fraction of indoxyl sulfate was markedly reduced at the end of hemodialysis. We hypothesized that solute binding might be pH-dependent and attributed the changes in free solute concentration to the higher serum pH observed at the end of standard hemodialysis with dialysis buffer bicarbonate concentration greater than 35 mmol/L...
2018: PloS One
https://www.readbyqxmd.com/read/29444900/extended-duration-nocturnal-hemodialysis-and-changes-in-plasma-metabolite-profiles
#8
Sahir Kalim, Ron Wald, Andrew T Yan, Marc B Goldstein, Mercedeh Kiaii, Dihua Xu, Anders H Berg, Clary Clish, Ravi Thadhani, Eugene P Rhee, Jeffrey Perl
BACKGROUND AND OBJECTIVES: In-center, extended duration nocturnal hemodialysis has been associated with variable clinical benefits, but the effect of extended duration hemodialysis on many established uremic solutes and other components of the metabolome is unknown. We determined the magnitude of change in metabolite profiles for patients on extended duration nocturnal hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a 52-week prospective, observational study, we followed 33 patients receiving conventional thrice weekly hemodialysis who converted to nocturnal hemodialysis (7-8 hours per session, three times per week)...
February 14, 2018: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29441989/modulated-function-of-multidrug-resistance-associated-proteins-in-cisplatin-induced-acute-renal-failure-rats
#9
A Matsushima, K Oda, N Mori, T Murakami
The effect of cisplatin-induced acute renal failure (ARF) on the function and expression of multidrug resistanceassociated proteins (MRPs) was evaluated in rats. Rats received an intraperitoneal injection of cisplatin (9 mg/kg), and the induction of ARF state with high plasma concentrations of indoxyl sulfate and creatinine was observed 72 h after cisplatin treatment. The function of MRPs in the liver, kidney and brain was evaluated by measuring the tissue accumulation and biliary excretion of 2,4-dintrophenyl-S-glutathione (DNP-SG), a substrate for MRPs, after administration of 1-chloro-2,4-dintrobenzene (CDNB), a precursor of DNP-SG, in rats...
April 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29439931/does-low-protein-diet-influence-the-uremic-toxin-serum-levels-from-the-gut-microbiota-in-nondialysis-chronic-kidney-disease-patients
#10
Ana Paula Black, Juliana S Anjos, Ludmila Cardozo, Flávia L Carmo, Carla J Dolenga, Lia S Nakao, Dennis de Carvalho Ferreira, Alexandre Rosado, José Carlos Carraro Eduardo, Denise Mafra
OBJECTIVES: To evaluate the effects of low-protein diet (LPD) on uremic toxins and the gut microbiota profile in nondialysis chronic kidney disease (CKD) patients. DESIGN AND METHODS: Longitudinal study with 30 nondialysis CKD patients (stage 3-4) undergoing LPD for 6 months. Adherence to the diet was evaluated based on the calculation of protein equivalent of nitrogen appearance from the 24-hour urine analysis. Good adherence to LPD was considered when protein intake was from 90% to 110% of the prescribed amount (0...
February 10, 2018: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/29428659/removal-of-indoxyl-sulfate-by-water-soluble-poly-cyclodextrins-in-dialysis
#11
Jingyu Li, Lulu Han, Shuxin Liu, Sai He, Yaming Cao, Jian Xie, Lingyun Jia
Indoxyl sulfate (IS) is a uremic toxin related to the progression of chronic kidney diseases. Removal of IS from the plasma would reduce the risk of cardiovascular disease. In this study, crosslinked poly-β-cyclodextrins (PCDs) were used as a water-soluble adsorbent agent for IS in dialysis for the first time. The molecular weight of PCDs was found to be proportional to the crosslinking time between β-cyclodextrin monomers and epichlorohydrin, yet the proportion of β-cyclodextrin that reacted with epichlorohydrin decreased...
January 31, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29428089/plasma-indoxyl-sulfate-concentration-predicts-progression-of-chronic-kidney-disease-in-dogs-and-cats
#12
C N Chen, C C Chou, P S J Tsai, Y J Lee
Indoxyl sulfate is a protein-bound uremic toxin that increases as the severity of impaired renal function increases in humans, laboratory animals, dogs and cats. An elevation of indoxyl sulfate is related to prognosis among people with chronic kidney disease. However, whether indoxyl sulfate is able to predict the progression of chronic kidney disease in dogs and cats has not been previously studied. In the present study, 58 cats and 36 dogs with chronic kidney disease were enrolled. Plasma indoxyl sulfate was measured by high performance liquid chromatography...
February 2018: Veterinary Journal
https://www.readbyqxmd.com/read/29395338/aryl-hydrocarbon-receptor-is-activated-in-patients-and-mice-with-chronic-kidney-disease
#13
Laetitia Dou, Stéphane Poitevin, Marion Sallée, Tawfik Addi, Bertrand Gondouin, Nathalie McKay, Michael S Denison, Noémie Jourde-Chiche, Ariane Duval-Sabatier, Claire Cerini, Philippe Brunet, Françoise Dignat-George, Stéphane Burtey
Patients with chronic kidney disease (CKD) are exposed to uremic toxins and have an increased risk of cardiovascular disease. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AHR). These toxins induce a vascular procoagulant phenotype. Here we investigated AHR activation in patients with CKD and in a murine model of CKD. We performed a prospective study in 116 patients with CKD stage 3 to 5D and measured the AHR-Activating Potential of serum by bioassay...
April 2018: Kidney International
https://www.readbyqxmd.com/read/29380555/the-double-edged-sword-of-endoplasmic-reticulum-stress-in-uremic-sarcopenia-through-myogenesis-perturbation
#14
Jia-Rong Jheng, Yuan-Siao Chen, Un Iong Ao, Ding-Cheng Chan, Jenq-Wen Huang, Kuang-Yu Hung, Der-Cheng Tarng, Chih-Kang Chiang
BACKGROUNDS: Sarcopenia is the age-related degeneration characterized with the decline of skeletal muscle mass, strength, and function. The imbalance of protein synthesis and degradation which jeopardizes immune, hormone regulation, and muscle-motor neuron connection is the main cause of sarcopenia. There is limited knowledge regarding molecular mechanism of sarcopenia. As the endoplasmic reticulum is the control centre of the protein syntheses and degradation, we hypothesized that endoplasmic reticulum stress and unfolded protein response (UPR) play an important in the development of sarcopenia...
January 29, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29371912/the-regulation-of-nlrp3-inflammasome-expression-during-the-development-of-cardiac-contractile-dysfunction-in-chronic-kidney-disease
#15
Li-Han Chin, Yu-Juei Hsu, Shih-Che Hsu, Yen-Hui Chen, Yung-Lung Chang, Shih-Ming Huang, Chien-Sung Tsai, Chih-Yuan Lin
Chronic inflammation plays a crucial role in the long-term complications in patients with chronic kidney disease (CKD). This study aimed to assess the role of NLR pyrin domain-containing protein (NLRP3) inflammasome in cardiac contractile dysfunctions in CKD. The cardiac contractile function was evaluated and the expression of NLRP3 inflammasome and related cytokines in the heart was assessed in a murine sham-operated and 5/6 nephrectomy CKD model in vivo. In vitro, H9c2 cells were treated with uremic toxin indoxyl sulfate (IS), with or without NLRP3 inflammasome inhibition, which was achieved by using small interfering RNA (siRNA)-mediated knockdown of the NLRP3 gene...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29363331/enalapril-decreases-rat-plasma-concentration-of-tmao-a-gut-bacteria-derived-cardiovascular-marker
#16
Marek Konop, Marek Radkowski, Marta Grochowska, Karol Perlejewski, Emilia Samborowska, Marcin Ufnal
INTRODUCTION: Increased plasma level of trimethylamine N-oxide (TMAO), a bacterial metabolite of choline, is associated with an increased cardiovascular risk. Indoxyl sulfate, a bacterial metabolite of tryptophan, is thought to be associated with higher mortality in cardiorenal syndrome. We hypothesized that enalapril, a well-established drug reducing cardiovascular mortality, may affect the plasma level of gut bacteria-derived metabolites and gut bacteria composition. MATERIALS AND METHODS: 14-16-week-old Wistar rats were maintained either on water (controls) or water solution of enalapril for two weeks (5...
February 7, 2018: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/29343519/uremic-solute-aryl-hydrocarbon-receptor-tissue-factor-axis-associates-with-thrombosis-after-vascular-injury-in-humans
#17
Vijaya B Kolachalama, Moshe Shashar, Faisal Alousi, Sowmya Shivanna, Keshab Rijal, Mostafa E Belghasem, Joshua Walker, Shinobu Matsuura, Gary H Chang, C Michael Gibson, Laura M Dember, Jean M Francis, Katya Ravid, Vipul C Chitalia
Individuals with CKD are particularly predisposed to thrombosis after vascular injury. Using mouse models, we recently described indoxyl sulfate, a tryptophan metabolite retained in CKD and an activator of tissue factor (TF) through aryl hydrocarbon receptor (AHR) signaling, as an inducer of thrombosis across the CKD spectrum. However, the translation of findings from animal models to humans is often challenging. Here, we investigated the uremic solute-AHR-TF thrombosis axis in two human cohorts, using a targeted metabolomics approach to probe a set of tryptophan products and high-throughput assays to measure AHR and TF activity...
January 17, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29316724/biochemical-and-clinical-impact-of-organic-uremic-retention-solutes-a-comprehensive-update
#18
REVIEW
Raymond Vanholder, Anneleen Pletinck, Eva Schepers, Griet Glorieux
In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered...
January 8, 2018: Toxins
https://www.readbyqxmd.com/read/29311647/-pro-renin-receptor-is-involved-in-mesangial-fibrosis-and-matrix-expansion
#19
Kaori Narumi, Emiko Sato, Takuo Hirose, Tae Yamamoto, Takashi Nakamichi, Mariko Miyazaki, Hiroshi Sato, Sadayoshi Ito
(Pro)renin receptor [(P)RR] is expressed in the kidney and is involved in renal injury. Although (P)RR is activated by indoxyl sulfate (IS) and may be related to renal injury, the details remain unclear. We used mouse mesangial cell line SV40 MES13 to investigate the association of (P)RR with mesangial fibrosis or expansion. Furthermore, we examined the correlation between serum soluble (P)RR [s(P)RR] and various laboratory data including serum IS, a uremic toxin that induces renal fibrosis through (P)RR, and pathological indices in chronic kidney disease and particularly in IgA nephropathy patients...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29290351/red-meat-intake-in-chronic-kidney-disease-patients-two-sides-of-the-coin
#20
REVIEW
Denise Mafra, Natalia A Borges, Ludmila Ferreira Medeiros de Franca Cardozo, Juliana S Anjos, Ana Paula Black, Cristiane Moraes, Peter Bergman, Bengt Lindholm, Peter Stenvinkel
Red meat is an important dietary source of high biological value protein and micronutrients such as vitamins, iron, and zinc that exert many beneficial functions. However, high consumption of animal protein sources, especially red meat, results in an increased intake of saturated fat, cholesterol, iron, and salt, as well as an excessive acid load. Red meat intake may lead to an elevated production of uremic toxins by the gut microbiota, such as trimethylamine n-oxide (TMAO), indoxyl sulfate, and p-cresyl sulfate...
February 2018: Nutrition
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