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https://www.readbyqxmd.com/read/28747155/indole-3-acetic-acid-indoxyl-sulfate-and-paracresyl-sulfate-do-not-influence-anemia-parameters-in-hemodialysis-patients
#1
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/28738836/metabolism-associated-danger-signal-induced-immune-response-and-reverse-immune-checkpoint-activated-cd40-monocyte-differentiation
#2
REVIEW
Jin Dai, Pu Fang, Jason Saredy, Hang Xi, Cueto Ramon, William Yang, Eric T Choi, Yong Ji, Wei Mao, Xiaofeng Yang, Hong Wang
Adaptive immunity is critical for disease progression and modulates T cell (TC) and antigen-presenting cell (APC) functions. Three signals were initially proposed for adaptive immune activation: signal 1 antigen recognition, signal 2 co-stimulation or co-inhibition, and signal 3 cytokine stimulation. In this article, we propose to term signal 2 as an immune checkpoint, which describes interactions of paired molecules leading to stimulation (stimulatory immune checkpoint) or inhibition (inhibitory immune checkpoint) of an immune response...
July 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28726627/mucus-activatable-shiga-toxin-genotype-stx2d-in-escherichia-coli-o157-h7
#3
Sergio Sánchez, María Teresa Llorente, Laura Herrera-León, Raquel Ramiro, Sandra Nebreda, María Antonia Remacha, Silvia Herrera-León
We identified the mucus-activatable Shiga toxin genotype stx2d in the most common hemolytic uremic syndrome-associated Escherichia coli serotype, O157:H7. stx2d was detected in a strain isolated from a 2-year-old boy with bloody diarrhea in Spain, and whole-genome sequencing was used to confirm and fully characterize the strain.
August 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28725563/atypical-hemolytic-uremic-syndrome-triggered-by-varicella-infection
#4
Pauline Condom, Jean-Michel Mansuy, Stéphane Decramer, Jacques Izopet, Catherine Mengelle
Varicella Zoster Virus (VZV) is a well-known virus that belongs to the Herpesviridae family which induces a self-limited disease except in specific cases in particular among stem cell transplant patients. This virus is not known however to trigger atypical Hemolytic Uremic Syndrome (aHUS). Here we report the case of a six-year-old boy who was hospitalized with fever and abdominal pains associated to pruritic and vesicular rash, thrombocytopenia and acute renal failure. He was diagnosed with aHUS precipitated by varicella virus...
2017: IDCases
https://www.readbyqxmd.com/read/28718802/ouabain-protects-human-renal-cells-against-the-cytotoxic-effects-of-shiga-toxin-type-2-and-subtilase-cytotoxin
#5
María M Amaral, Magalí C Girard, Romina S Álvarez, Adrienne W Paton, James C Paton, Horacio A Repetto, Flavia Sacerdoti, Cristina A Ibarra
Hemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in children. The majority of cases are associated with Shiga toxin (Stx)-producing Escherichia coli (STEC). In Argentina, HUS is endemic and presents the highest incidence rate in the world. STEC strains expressing Stx type 2 (Stx2) are responsible for the most severe cases of this pathology. Subtilase cytotoxin (SubAB) is another STEC virulence factor that may contribute to HUS pathogenesis. To date, neither a licensed vaccine nor effective therapy for HUS is available for humans...
July 18, 2017: Toxins
https://www.readbyqxmd.com/read/28711159/-hemolytic-and-uremic-syndrome-and-related-thrombotic-microangiopathies-epidemiology-pathophysiology-and-clinics
#6
C Rafat, P Coppo, F Fakhouri, V Frémeaux-Bacchi, C Loirat, J Zuber, E Rondeau
Thrombotic microangiopathies (TMA) represent an eclectic group of conditions, which share hemolytic anemia and thrombocytopenia as a common defining basis. Remarkable breakthroughs in the physiopathological setting have allowed for a thorough recomposition of the disparate syndromes, which form the constellation of TMA. In this view, clinicians now discriminate thrombocytopenic thrombotic purpura (TTP) defined by a severe deficiency in ADAMTS13, which is rarely associated with a severe renal involvement and the hemolytic and uremic syndrome (HUS) in which renal impairment is the most prominent clinical feature...
July 12, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28698529/naturally-occurring-compounds-new-potential-weapons-against-oxidative-stress-in-chronic-kidney-disease
#7
REVIEW
Lorenzo Signorini, Simona Granata, Antonio Lupo, Gianluigi Zaza
Oxidative stress is a well-described imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system of cells and tissues. The overproduction of free radicals damages all components of the cell (proteins, lipids, nucleic acids) and modifies their physiological functions. As widely described, this condition is a biochemical hallmark of chronic kidney disease (CKD) and may dramatically influence the progression of renal impairment and the onset/development of major systemic comorbidities including cardiovascular diseases...
July 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28696247/microrna-92a-mediates-endothelial-dysfunction-in-ckd
#8
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
#9
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/28687651/characterization-of-shiga-toxin-producing-escherichia-coli-strains-of-o91-serogroup-isolated-from-food-and-environmental-samples
#10
Peter C H Feng, Sabine Delannoy, David W Lacher, Joseph M Bosilevac, Patrick Fach, Lothar Beutin
Shiga toxin-producing Escherichia coli (STEC) of the O91:H21 serotype has caused severe infections including hemolytic uremic syndrome. Strains of the O91 serogroup have been isolated from food, animals and the environment worldwide, but are not well characterized. We used a microarray and other molecular assays to examine 49 O91 strains (environmental, food and clinical) for virulence potential and phylogenetic relationships. Most of the isolates were identified to be strains of O91:H21 and O91:H14 serotype, with a few O91:H10 strains and one O91:H9 strain...
July 7, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28682564/-complement-factor-b-mutation-in-atypical-hemolytic-uremic-syndrome-rare-cause-of-rare-disease
#11
Luca Visconti, Valeria Cernaro, Gianluigi Ardissino, Martina Sgarbanti, Domenico Ferrara, Giuseppe Visconti, Domenico Santoro, Michele Buemi
Hemolytic uremic syndrome (HUS) is a rare disease characterized by microangiopathic hemolysis, platelet consumption and multiple organ failure with predominant renal involvement. In the most of cases (85-90%), it is associated with enteric infection due to Shiga-toxin or verocytotoxin (STEC-VTEC)-producer Escherichia coli. Rarely, in about 10-15% of cases, HUS develops in the presence of a disorder of alternative complement pathway regulation and it is defined atypical (aHUS). We describe the case of a 65-year-old man who came to our attention with a clinical presentation of aHUS and a clinical course characterized by rapidly progressive acute renal failure (ARF), which required renal replacement treatments, and by a stable clinical picture of hematological impairment as a marker of a non-severe and self-limiting form...
April 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28682026/-clinical-management-of-anemia-in-patients-with-ckd
#12
Rodolfo Fernando Rivera, Maria Teresa Sciarrone Alibrandi, Luca Di Lullo, Fulvio Fioccari
Anemia is a frequent complication in chronic kidney disease (CKD), and it is often accompanied by various clinical symptoms. The primary cause of anemia in CKD patients is the reduction in the erythropoietin production, which results in a decrease of signaling molecule that stimulates red blood cell production. Other possible causes of anemia in CKD include iron deficiency, inflammation, and the accumulation of uremic toxin. This chapter focuses the discussion on the strategy of the management of anemia in patients with CKD...
March 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28680376/dendritic-cell-dysfunction-in-patients-with-end-stage-renal-disease
#13
REVIEW
Ji Ung Kim, Miyeon Kim, Sinae Kim, Tam Thanh Nguyen, Eunhye Kim, Siyoung Lee, Soohyun Kim, Hyunwoo Kim
End-stage renal disease (ESRD) with immune disorder involves complex interactions between the innate and adaptive immune responses. ESRD is associated with various alterations in immune function such as a reduction in polymorphonuclear leukocyte bactericidal activity, a suppression of lymphocyte proliferative response to stimuli, and a malfunction of cell-mediated immunity at the molecular level. ESRD also increases patients' propensity for infections and malignancies as well as causing a diminished response to vaccination...
June 2017: Immune Network
https://www.readbyqxmd.com/read/28668284/is-there-a-role-for-diaphoresis-therapy-for-advanced-chronic-kidney-disease-patients
#14
REVIEW
Norio Hanafusa, Bereket Tessema Lodebo, Anuja Shah, Joel D Kopple
Diaphoresis therapy to remove water and solutes for the treatment of advanced chronic kidney disease (CKD) and chronic dialysis patients is an inadequately characterized treatment that was first reported over 50 years ago. Intensive diaphoresis, induced by heat treatment with saunas (dry heat) or hot baths (wet heat), can substantially increase cutaneous losses of water, urea, sodium, potassium, chloride, lactate, and possibly other solutes. How effectively diaphoresis therapy might remove many uremic toxins is not known...
June 28, 2017: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/28667460/prediction-of-the-effect-of-renal-impairment-on-the-pharmacokinetics-of-new-drugs
#15
Elisa Borella, Italo Poggesi, Paolo Magni
INTRODUCTION: Renal impairment may have a significant impact on the pharmacokinetics of drugs. Ad hoc studies in subjects with renal impairment are required by the regulatory authorities to propose dose adjustments in these subjects, to find a dosing regimen able to provide a systemic exposure similar to those in subjects with a normal renal function given the relevant clinical dose. METHODS: To evaluate the main descriptors and establish a predictive model of the effect of renal impairment on the exposure of new drugs, we considered 73 marketed drugs, for which studies in subjects with different degrees of renal impairment were available in the literature...
June 30, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28667064/disposition-and-clinical-implications-of-protein-bound-uremic-toxins
#16
REVIEW
Jitske Jansen, Joachim Jankowski, Prathibha R Gajjala, Jack F M Wetzels, Rosalinde Masereeuw
In patients with chronic kidney disease (CKD), adequate renal clearance is compromised, resulting in the accumulation of a plethora of uremic solutes. These uremic retention solutes, also named uremic toxins, are a heterogeneous group of organic compounds with intrinsic biological activities, many of which are too large to be filtered and/or are protein bound. The renal excretion of protein-bound toxins depends largely on active tubular secretion, which shifts the binding and allows for active secretion of the free fraction...
July 15, 2017: Clinical Science (1979-)
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
#17
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/28655071/melatonin-rescues-mesenchymal-stem-cells-from-senescence-induced-by-the-uremic-toxin-p-cresol-via-inhibiting-mtor-dependent-autophagy
#18
Seung Pil Yun, Yong-Seok Han, Jun Hee Lee, Sang Min Kim, Sang Hun Lee
p-Cresol, found at high concentrations in the serum of chronic kidney failure patients, is known to cause cell senescence and other complications in different parts of the body. p-Cresol is thought to mediate cytotoxic effects through the induction of autophagy response. However, toxic effects of p-cresol on mesenchymal stem cells have not been elucidated. Thus, we aimed to investigate whether p-cresol induces senescence of mesenchymal stem cells, and whether melatonin can ameliorate abnormal autophagy response caused by p-cresol...
June 27, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28654798/the-impact-of-gut-microbiota-on-kidney-function-and-pathogenesis
#19
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...
June 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28652624/serum-hepcidin-may-be-a-novel-uremic-toxin-which-might-be-related-to-erythropoietin-resistance
#20
Sung Woo Lee, Jeong Min Kim, Hye Jin Lim, Young-Hwan Hwang, Soo Wan Kim, Wookyung Chung, Kook-Hwan Oh, Curie Ahn, Kyu-Beck Lee, Su Ah Sung
The clinical importance of serum hepcidin in non-dialysis chronic kidney disease (CKD) patients is unclear. The database of a large-scale multicentre prospective study in Korea of 2238 patients enrolled from 2011-2016 was analysed. After excluding patients with missing serum hepcidin (n = 125) and haemoglobin (n = 23) levels, the study included 2090 non-dialysis CKD patients. Markers of inflammation and iron status were positively associated with serum hepcidin level, regardless of CKD stage. However, estimated glomerular filtration rate was inversely associated with serum hepcidin level, particularly in patients with CKD stages 3b-5 but not in those with CKD stages 1-3a...
June 26, 2017: Scientific Reports
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