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Uremic toxins

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https://www.readbyqxmd.com/read/28542036/a-survey-of-renal-impairment-pharmacokinetic-studies-for-new-oncology-drug-approvals-in-the-usa-from-2010-to-early-2015-a-focus-on-development-strategies-and-future-directions
#1
Jim J Xiao, Jiyun S Chen, Bert L Lum, Richard A Graham
The US Food and Drug Administration (FDA) issued a guidance document in 2010 on pharmacokinetic (PK) studies in renal impairment (RI) on the basis of observations that substances such as uremic toxins might result in altered drug metabolism and excretion. No specific recommendations for oncology drugs were included. We surveyed the publicly available FDA review documents of 29 small molecule oncology drugs approved between 2010 and the first quarter of 2015. The objectives were as follows: (i) summarize the impact of RI on PK at the time of the initial new drug application; (ii) identify limitations of the guidance; and (iii) outline an integrated approach to study the impact of RI on these drugs...
May 24, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28537846/uremic-toxins-affect-the-imbalance-of-redox-state-and-overexpression-of-prolyl-hydroxylase-2-in-human-adipose-tissue-derived-mesenchymal-stem-cells-involved-in-wound-healing
#2
Vuong Cat Khanh, Kinuko Ohneda, Toshiki Kato, Toshiharu Yamashita, Fujio Sato, Kana Tachi, Osamu Ohneda
Chronic kidney disease (CKD) results in a delay in wound healing because of its complications such as uremia, anemia, and fluid overload. Mesenchymal stem cells (MSCs) are considered to be a candidate for wound healing because of the ability to recruit many types of cells. However, it is still unclear whether the CKD-adipose tissue-derived MSCs (CKD-AT-MSCs) have the same function in wound healing as healthy donor-derived normal AT-MSCs (nAT-MSCs). In this study, we found that uremic toxins induced elevated reactive oxygen species (ROS) expression in nAT-MSCs, resulting in the reduced expression of hypoxia-inducible factor-1α (HIF-1α) under hypoxic conditions...
May 24, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28535525/expanded-hemodialysis-a-new-therapy-for-a-new-class-of-membranes
#3
Claudio Ronco, Gaetano La Manna
A wide spectrum of molecules is retained in end-stage kidney disease, normally defined as uremic toxins. These solutes have different molecular weights and radii. Current dialysis membranes and techniques only remove solutes in the range of 50-15,000 Da, with limited or no capability to remove solutes in the middle to high molecular weight range (up to 50,000 Da). Improved removal has been obtained with high cut-off (HCO) membranes, with albumin loss representing a limitation to their practical application...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28535204/colocalization-of-receptors-for-shiga-toxins-with-lipid-rafts-in-primary-human-renal-glomerular-endothelial-cells-and-influence-of-d-pdmp-on-synthesis-and-distribution-of-glycosphingolipid-receptors
#4
Nadine Legros, Gottfried Pohlentz, Jana Runde, Stefanie Dusny, Hans-Ulrich Humpf, Helge Karch, Johannes Müthing
Damage of human renal glomerular endothelial cells (HRGECs) of the kidney represents the linchpin in the pathogenesis of the hemolytic uremic syndrome (HUS) caused by Shiga toxins (Stxs) of enterohemorrhagic Escherichia coli (EHEC). We performed a comprehensive structural analysis of the Stx receptor glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer, Galα4alβ4Glcβ1Cer) and globotetraosylceramide (Gb4Cer, GalNAcβ3Galα4Galβ4Glcβ1Cer) and their distribution in lipid raft analogue detergent-resistant membranes (DRMs) and nonDRMs prepared from primary HRGECs...
May 23, 2017: Glycobiology
https://www.readbyqxmd.com/read/28534196/in-silico-analysis-of-shiga-toxins-stxs-to-identify-new-potential-vaccine-targets-for-shiga-toxin-producing-escherichia-coli
#5
Maryam Golshani, Mana Oloomi, Saeid Bouzari
Shiga toxins belong to a family of structurally and functionally related toxins serving as the main virulence factors for pathogenicity of the Shiga toxin-producing Escherichia coli (STEC) associating with Hemolytic uremic syndrome (HUS). At present, there is no effective treatment or prevention for HUS. The aim of the present study was to find conserved regions within the amino acid sequences of Stx1, Stx2 (Shiga toxin) and their variants. In this regard, In-silico identification of conformational continuous B cell and T-cell epitopes was performed in order to introduce new potential vaccine candidates...
December 2016: In Silico Pharmacology
https://www.readbyqxmd.com/read/28529915/hemolytic-uremic-syndrome-in-adults-a-case-report
#6
Fabiel Gerardo Pérez-Cruz, Patricia Villa-Díaz, María Consuelo Pintado-Delgado, María Loreto Fernández Rodríguez, Ana Blasco-Martínez, María Pérez-Fernández
Thrombotic microangiopathies (TMA) are microvascular occlusive disorders characterized by platelet aggregation and mechanical damage to erythrocytes, clinically characterized by microangiopatic haemolytic anemia, thrombocytopenia and organ injury. We are reporting a case of a woman patient with severe hemolytic uremic syndrome associated to infectious diarrhoea caused by Shiga toxin-producing pathogen, who were admitted to our intensive care unit. The patient described developed as organ injury, neurological failure and acute renal failure, with need of haemodialysis technique...
May 4, 2017: World Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/28528271/exploring-binding-characteristics-and-the-related-competition-of-different-protein-bound-uremic-toxins
#7
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/28524108/-uremic-toxin-section-in-the-journal-toxins-a-powerful-tool-to-bundle-and-advance-knowledge-on-uremia
#8
EDITORIAL
https://www.readbyqxmd.com/read/28501302/measuring-the-patient-response-to-dialysis-therapy-hemodiafiltration-and-clinical-trials
#9
Mark R Marshall
There is a strong biological plausibility for benefit from removal of larger uremic toxins and increasing positive clinical experience with hemodiafiltration. However, evidence supporting hemodiafiltration is not definitive with studies that are often limited by serious methodological shortcomings. Morena et al. show that hemodiafiltration may prevent intradialytic hypotension, albeit in a study that also has some shortcomings. Ongoing research for hemodiafiltration is still needed through high-quality clinical trials that adhere to standards for clinical trial conduct and reporting...
June 2017: Kidney International
https://www.readbyqxmd.com/read/28498348/nutrients-turned-into-toxins-microbiota-modulation-of-nutrient-properties-in-chronic-kidney-disease
#10
REVIEW
Raul Fernandez-Prado, Raquel Esteras, Maria Vanessa Perez-Gomez, Carolina Gracia-Iguacel, Emilio Gonzalez-Parra, Ana B Sanz, Alberto Ortiz, Maria Dolores Sanchez-Niño
In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects...
May 12, 2017: Nutrients
https://www.readbyqxmd.com/read/28497092/the-relationship-between-dialysis-adequacy-and-serum-uric-acid-in-dialysis-patients-a-cross-sectional-multi-center-study-in-iranian-hemodialysis-centers
#11
Eghlim Nemati, Arezoo Khosravi, Behzad Einollahi, Mehdi Meshkati, Mehrdad Taghipour, Shahin Abbaszadeh
Introduction: Uric acid is one of the most significant uremic toxins accumulating in chronic renal failure patients treated with standard dialysis. Its clearance has not any exact relation with urea and creatinine clearance. Objectives: The aim of this study was to investigate the relationship between adequacy of dialysis and serum level of uric acid in dialysis patients of some dialysis centers in Iran. Patients and Methods: In this study 1271 hemodialysis patients who have been treated for more than 3 months were evaluated...
2017: Journal of Renal Injury Prevention
https://www.readbyqxmd.com/read/28490014/aryl-hydrocarbon-receptor-activation-in-chronic-kidney-disease-role-of-uremic-toxins
#12
Jessyca S Brito, Natália A Borges, Marta Esgalhado, D''Angelo C Magliano, Christophe O Soulage, Denise Mafra
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in the expression of xenobiotic-metabolizing enzymes, inflammatory cytokines and adhesion molecules. Uremic toxins such as indoxyl sulfate and indole acetic acid are derived from tryptophan fermentation by gut microbiota; they accumulate in patients with chronic kidney disease (CKD) on haemodialysis and have recently emerged as potent ligands of AhR. Therefore, AhR can serve as a mediator in inflammation and cardiovascular diseases in these patients...
May 11, 2017: Nephron
https://www.readbyqxmd.com/read/28484827/-hot-rods-in-the-icu-what-is-the-antibiotic-mileage-of-your-renal-replacement-therapy
#13
REVIEW
J T Kielstein, A K Kruse, N Anderson, H Vaitiekunas, S Scherneck
We would neither be disappointed nor upset if the gas mileage on the sticker of a car didn't match our personal, real-life fuel consumption. Depending on our daily route to work, our style of accelerating and the number of passengers in our carpool, the gas mileage will vary. As soon as the falcon wing door of our car is closed and entrance to the ICU is granted, we tend to forget all of this, even though another hot rod is waiting there for us. Renal replacement therapy is like a car; it fulfills goals, such as the removal of uremic toxins and accumulated fluids, but it also "consumes" (removes) antibiotics...
May 8, 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28483384/-online-hemodiafiltration-practical-aspects-safety-and-efficacy
#14
Bernard Canaud, Leïla Chénine, Hélène Leray-Moraguès, Laure Patrier, Annie Rodriguez, A Gontier-Picard, Marion Moréna
Purification of high molecular uremic toxins by conventional hemodialysis is limited. It remains associated with a high morbidity and excessively high mortality. Online hemodiafiltration using a high permeability hemodiafilter, an ultrapure dialysate, and which tends to maximize substitution volumes, provides a high efficiency and low bio-incompatibility renal supplementation. Regular use of online hemodiafiltration is associated with reduced morbidity (reduction of intradialytic hypotension episodes, improved blood pressure control, reduced inflammatory profile, better anemia correction and prevention of β2-microglobulin-associated amyloidosis)...
May 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28472795/role-of-organic-anion-transporters-in-the-uptake-of-protein-bound-uremic-toxins-by-human-endothelial-cells-and-monocyte-chemoattractant-protein-1-expression
#15
Giane Favretto, Lauro M Souza, Paulo C Gregório, Regiane S Cunha, Rayana A P Maciel, Guilherme L Sassaki, Maria G Toledo, Roberto Pecoits-Filho, Wesley M Souza, Andréa E M Stinghen
Organic anion transporters (OATs) are involved in the uptake of uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS), which play a role in endothelial dysfunction in patients with chronic kidney diseases (CKD). In this study, we investigated the role of OAT1 and OAT3 in the uptake of PCS and IS into human endothelial cells. PCS was synthesized via p-cresol sulfation and characterized using analytical methods. The cells were treated with PCS and IS in the absence and presence of probenecid (Pb), an OAT inhibitor...
May 5, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28469807/protein-bound-p-cresol-inhibits-human-umbilical-vein-endothelial-cell-proliferation-by-inducing-cell-cycle-arrest-at-g0-g1
#16
Li Li, Jing Li, Xun Li, Fa-Huan Yuan
P-cresol is a typical protein-bound uremic toxin, which is retained in patients with renal failure. It is not known whether protein-bound P-cresol exhibits the toxicity in humans. This study aims to investigate the endothelial toxicity of protein-bound P-cresol. Cultured human umbilical vein endothelial cells (HUVEC) were treated with unbound or human serum albumin-bound (HSA, 4 g/dL), P-cresol (0, 20, 40, 80 μg/mL) for 24, 48, 72 h, respectively. Cell viability was determined by using cell counting kit-8 (CCK-8) assay...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28468236/non-traditional-aspects-of-renal-diets-focus-on-fiber-alkali-and-vitamin-k1-intake
#17
Adamasco Cupisti, Claudia D'Alessandro, Loreto Gesualdo, Carmela Cosola, Maurizio Gallieni, Maria Francesca Egidi, Maria Fusaro
Renal diets for advanced chronic kidney disease (CKD) are structured to achieve a lower protein, phosphate and sodium intake, while supplying adequate energy. The aim of this nutritional intervention is to prevent or correct signs, symptoms and complications of renal insufficiency, delaying the start of dialysis and preserving nutritional status. This paper focuses on three additional aspects of renal diets that can play an important role in the management of CKD patients: the vitamin K1 and fiber content, and the alkalizing potential...
April 29, 2017: Nutrients
https://www.readbyqxmd.com/read/28456922/nutritional-status-after-conversion-from-conventional-to-in-centre-nocturnal-hemodialysis
#18
Nazanin Noori, Andrew T Yan, Mercedeh Kiaii, Andrea Rathe, Marc B Goldstein, Olugbenga Bello, Ron Wald
INTRODUCTION: Recipients of conventional hemodialysis (CHD; 3-4 h/session, 3 times/week) experience volume expansion and nutritional impairment which may contribute to high mortality. Prolongation of sessions with in-centre nocturnal hemodialysis (INHD; 7-8 h/session, 3 times/week) may improve clinical outcomes by enhancement of ultrafiltration and uremic toxin removal. MATERIALS AND METHODS: In this prospective cohort study, 56 adult patients who were receiving maintenance CHD for at least 90 days were assigned to CHD (patients who remained in CHD) and INHD (patients who switched to INHD) groups...
April 29, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28452109/implications-of-albumin-leakage-for-survival-in-maintenance-hemodialysis-patients-a-7-year-observational-study
#19
Kojiro Nagai, Kenji Tsuchida, Noriyuki Ishihara, Naoto Minagawa, Go Ichien, Satoshi Yamada, Daisuke Hirose, Hiroyuki Michiwaki, Hiro-Omi Kanayama, Toshio Doi, Jun Minakuchi
Albumin leakage during hemodialysis (HD) presents a clinical dilemma. However, protein-binding uremic toxins are suggested to be responsible for increased mortality. No one has investigated the relationship between albumin leakage and mortality. Therefore, the purpose of this observational study was to analyze the association of albumin leakage with mortality in 690 HD patients who survived one year after enrollment. They were divided to three groups who received HD with large (3 g or more per HD session), middle (1 to 3 g) or small (less than 1 g) amount of albumin leakage, respectively...
April 27, 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28447417/diagnostic-approach-to-microangiopathic-hemolytic-disorders
#20
REVIEW
K Kottke-Marchant
Thrombotic micro-angiopathies (TMA) are a group of related disorders that are characterized by thrombosis of the microvasculature and associated organ dysfunction, and encompass congenital, acquired, and infectious etiologies. A hall mark of TMAs is the fragmentation of erythrocytes by the microvascular thrombi, resulting in a hemolytic anemia. There are several distinct pathophysiologies leading to microangiopathic hemolysis, ranging from decreased degradation of von Willebrand factor as seen in thrombotic thrombocytopenic purpura (TTP) to endothelial damage facilitated by Escherichia coli shiga toxin or complement dysregulation, seen in shiga toxin-related hemolytic-uremic syndrome (Stx-HUS) and complement-mediated TMA (also called atypical hemolytic-uremic syndrome), respectively...
May 2017: International Journal of Laboratory Hematology
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