Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets

Antibody-based immunotherapy targeting cytokines and atherothrombotic cardiovascular diseases

(2020) Hafid Ait-Oufella et al.   Archives of Cardiovascular Diseases

Trimethylamine-N-Oxide Promotes Vascular Calcification Through Activation of NLRP3 (Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3) Inflammasome and NF-κB (Nuclear Factor κB) Signals

(2020) Xiuli Zhang et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Targeted Inhibition of Gut Microbial Trimethylamine N-Oxide Production Reduces Renal Tubulointerstitial Fibrosis and Functional Impairment in a Murine Model of Chronic Kidney Disease

(2020) Nilaksh Gupta et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

The Emerging Role of Innate Immunity in Chronic Kidney Diseases

(2020) Philip Chiu-Tsun Tang et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells

(2020) Jia-Feng Chang et al.   Toxins

Asymmetric dimethylarginine (ADMA) accelerates renal cell fibrosis under high glucose condition through NOX4/ROS/ERK signaling pathway

(2020) Isaivani Jayachandran et al.   Scientific Reports

New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

(2020) Lili Sheng et al.   Frontiers in Physiology

ADMA: A Key Player in the Relationship between Vascular Dysfunction and Inflammation in Atherosclerosis

(2020) Laura Dowsett et al.   Journal of Clinical Medicine

Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production

(2020) Yingyi Wang et al.   Gut Microbes

Hippuric Acid Promotes Renal Fibrosis by Disrupting Redox Homeostasis via Facilitation of NRF2–KEAP1–CUL3 Interactions in Chronic Kidney Disease

(2020) Bowen Sun et al.   Antioxidants

Immunity and Inflammation in Atherosclerosis

(2019) Dennis Wolf et al.   CIRCULATION RESEARCH

Lactofermented Annurca Apple Puree as a Functional Food Indicated for the Control of Plasma Lipid and Oxidative Amine Levels: Results from a Randomised Clinical Trial

(2019) Gian Tenore et al.   Nutrients

Review of the efficacy of AST-120 (KREMEZIN®) on renal function in chronic kidney disease patients

(2019) Mayumi Asai et al.   RENAL FAILURE

Reduced asymmetric dimethylarginine accumulation through inhibition of the type I protein arginine methyltransferases promotes renal fibrosis in obstructed kidneys

(2019) Ming Wu et al.   FASEB JOURNAL

Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding Competitor

(2019) Magdalena Madero et al.   Clinical Journal of the American Society of Nephrology

Asymmetric (ADMA) and Symmetric (SDMA) Dimethylarginines in Chronic Kidney Disease: A Clinical Approach

(2019) Elena Oliva-Damaso et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Chronic Kidney Disease Diagnosis and Management

(2019) Teresa K. Chen et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Indoxyl sulfate‐induced calcification of vascular smooth muscle cells via the PI3K/Akt/NF‐κB signaling pathway

(2019) Xin He et al.   MICROSCOPY RESEARCH AND TECHNIQUE

Regulation and Effects of FGF23 in Chronic Kidney Disease

(2019) John Musgrove et al.   Annual Review of Physiology

The detrimental effect of asymmetric dimethylarginine on cholesterol efflux of macrophage foam cells: Role of the NOX/ROS signaling

(2019) Chia-Hui Chen et al.   FREE RADICAL BIOLOGY AND MEDICINE

Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic Target

(2019) Shengjie Yang et al.   Frontiers in Pharmacology

Quercetin protects the vascular endothelium against iron overload damages via ROS/ADMA/DDAHⅡ/eNOS/NO pathway

(2019) Xuepiao Chen et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Metabolic products of the intestinal microbiome and extremes of atherosclerosis

(2018) Chrysi Bogiatzi et al.   ATHEROSCLEROSIS

Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway

(2018) Jin Geng et al.   BIOMEDICINE & PHARMACOTHERAPY

IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis

(2018) Chia-Hung Chou et al.   CARDIOVASCULAR RESEARCH

Association between hippuric acid and left ventricular hypertrophy in maintenance hemodialysis patients

(2018) Teng-Hung Yu et al.   CLINICA CHIMICA ACTA

Exploring the Clinical Relevance of Providing Increased Removal of Large Middle Molecules

(2018) Martin Wolley et al.   Clinical Journal of the American Society of Nephrology

Interleukin-6 contributes to the increase in fibroblast growth factor 23 expression in acute and chronic kidney disease

(2018) Karina Durlacher-Betzer et al.   KIDNEY INTERNATIONAL

OUP accepted manuscript

(2018)   NEPHROLOGY DIALYSIS TRANSPLANTATION

Asymmetric dimethylarginine (ADMA) as an important risk factor for the increased cardiovascular diseases and heart failure in chronic kidney disease

(2018) Xiaohong Liu et al.   NITRIC OXIDE-BIOLOGY AND CHEMISTRY

Lactobacillus plantarum ZDY04 exhibits strain-specific property of lowering-TMAO via modulation of gut microbiota in mice

(2018) Liang Qiu et al.   Food & Function

Mediterranean Diet Score: Associations with Metabolic Products of the Intestinal Microbiome, Carotid Plaque Burden, and Renal Function

(2018) Michael Pignanelli et al.   Nutrients

Role of Uremic Toxins for Kidney, Cardiovascular, and Bone Dysfunction

(2018) Hideki Fujii et al.   Toxins

Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update

(2018) Raymond Vanholder et al.   Toxins

Effects of Probiotic Supplementation on Trimethylamine-N-Oxide Plasma Levels in Hemodialysis Patients: a Pilot Study

(2018) Natália A. Borges et al.   Probiotics and Antimicrobial Proteins

The uremic toxin hippurate promotes endothelial dysfunction via the activation of Drp1-mediated mitochondrial fission

(2018) Mengjie Huang et al.   Redox Biology

Captopril alleviates hypertension-induced renal damage, inflammation, and NF-κB activation

(2018) Zhongyuan Gan et al.   BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH

Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential

(2018) Adam B. Roberts et al.   NATURE MEDICINE

The role of klotho in chronic kidney disease

(2018) Di Zou et al.   BMC Nephrology

MicroRNA-92a Mediates Endothelial Dysfunction in CKD

(2017) Fenqing Shang et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

Tumour necrosis factor-alpha in uraemic serum promotes osteoblastic transition and calcification of vascular smooth muscle cells via extracellular signal-regulated kinases and activator protein 1/c-FOS-mediated induction of interleukin 6 expression

(2017) Daniel Zickler et al.   NEPHROLOGY DIALYSIS TRANSPLANTATION

Toxic Dimethylarginines: Asymmetric  Dimethylarginine (ADMA) and Symmetric  Dimethylarginine (SDMA)

(2017) You‐Lin Tain et al.   Toxins

p-Cresyl Sulfate

(2017) Tessa Gryp et al.   Toxins

Indoxyl Sulfate: A Novel Cardiovascular Risk Factor in Chronic Kidney Disease

(2017) Szu‐Chun Hung et al.   Journal of the American Heart Association

Gut Microbiota-Dependent Trimethylamine-N-oxide and Serum Biomarkers in Patients with T2DM and Advanced CKD

(2017) Mohammed Al-Obaide et al.   Journal of Clinical Medicine

Association Between Chronic Kidney Disease Progression and Cardiovascular Disease: Results from the CRIC Study

(2017) Mahboob Rahman et al.   AMERICAN JOURNAL OF NEPHROLOGY

Hippurate as a metabolomic marker of gut microbiome diversity: Modulation by diet and relationship to metabolic syndrome

(2017) Tess Pallister et al.   Scientific Reports

Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome

(2016) Xiaolei Sun et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial

(2016) M. Rossi et al.   Clinical Journal of the American Society of Nephrology

Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosisviamembrane TNF-α mediated NF-κB pathway

(2016) Wei Gao et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

p-Cresyl sulfate is associated with carotid arteriosclerosis in hemodialysis patients and promotes atherogenesis in apoE−/− mice

(2016) Ya J. Jing et al.   KIDNEY INTERNATIONAL

The effects of AST-120 on chronic kidney disease progression in the United States of America: a post hoc subgroup analysis of randomized controlled trials

(2016) Gerald Schulman et al.   BMC Nephrology

Indoxyl Sulfate—Review of Toxicity and Therapeutic Strategies

(2016) Sheldon Leong et al.   Toxins

Trimethylamine N‐Oxide Promotes Vascular Inflammation Through Signaling of Mitogen‐Activated Protein Kinase and Nuclear Factor‐κB

(2016) Marcus M. Seldin et al.   Journal of the American Heart Association

Untargeted plasma and tissue metabolomics in rats with chronic kidney disease given AST-120

(2016) Thomas J. Velenosi et al.   Scientific Reports

Asymmetric dimethylarginine (ADMA) in human blood: effects of extended haemodialysis in the critically ill patient with acute kidney injury, protein binding to human serum albumin and proteolysis by thermolysin

(2015) Mustafa Erinc Sitar et al.   AMINO ACIDS

Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis

(2015) Zeneng Wang et al.   CELL

The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition

(2015) Christoph Garbers et al.   CURRENT OPINION IN IMMUNOLOGY

High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome

(2015) Francesca De Filippis et al.   GUT

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

(2015) J. A. P. Tomlinson et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden

(2015) J. R. Stubbs et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

Vascular calcification in chronic kidney disease: an update

(2015) Georg Schlieper et al.   NEPHROLOGY DIALYSIS TRANSPLANTATION

Dietary protein-fiber ratio associates with circulating levels of indoxyl sulfate and p-cresyl sulfate in chronic kidney disease patients

(2015) M. Rossi et al.   NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES

Probiotic supplementation and trimethylamine-N-oxide production following a high-fat diet

(2015) Nabil E. Boutagy et al.   Obesity

Proximal tubular efflux transporters involved in renal excretion of p-cresyl sulfate and p-cresyl glucuronide: Implications for chronic kidney disease pathophysiology

(2015) Henricus A.M. Mutsaers et al.   TOXICOLOGY IN VITRO

Indoxyl sulfate induces oxidative stress and hypertrophy in cardiomyocytes by inhibiting the AMPK/UCP2 signaling pathway

(2015) Ke Yang et al.   TOXICOLOGY LETTERS

Continuous Reduction of Protein-Bound Uraemic Toxins with Improved Oxidative Stress by Using the Oral Charcoal Adsorbent AST-120 in Haemodialysis Patients

(2015) Suguru Yamamoto et al.   Scientific Reports

Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of Chronic Kidney Disease and during Hemodialysis

(2015) Olivier Deltombe et al.   Toxins

The Influence of Dietary Protein Intake on Mammalian Tryptophan and Phenolic Metabolites

(2015) Ruben Poesen et al.   PLoS One

L-citrulline for protection of endothelial function from ADMA–induced injury in porcine coronary artery

(2015) Chao Xuan et al.   Scientific Reports

Expansion of Urease- and Uricase-Containing, Indole- and p-Cresol-Forming and Contraction of Short-Chain Fatty Acid-Producing Intestinal Microbiota in ESRD

(2014) Jakk Wong et al.   AMERICAN JOURNAL OF NEPHROLOGY

γ-Butyrobetaine Is a Proatherogenic Intermediate in Gut Microbial Metabolism of L -Carnitine to TMAO

(2014) Robert A. Koeth et al.   Cell Metabolism

Vascular Calcification in Chronic Kidney Disease: Role of Disordered Mineral Metabolism

(2014) Shyamal Palit et al.   CURRENT PHARMACEUTICAL DESIGN

Interleukin-6 and its receptors: A highly regulated and dynamic system

(2014) Janina Wolf et al.   CYTOKINE

Randomized Placebo-Controlled EPPIC Trials of AST-120 in CKD

(2014) G. Schulman et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

Asymmetric Dimethylarginine and Progression of Chronic Kidney Disease - a One-Year Follow-Up Study

(2014) Jaromír Eiselt et al.   KIDNEY & BLOOD PRESSURE RESEARCH

Suppression of intestinal microbiota-dependent production of pro-atherogenic trimethylamine N-oxide by shifting L-carnitine microbial degradation

(2014) Janis Kuka et al.   LIFE SCIENCES

Baseline Serum Interleukin-6 Predicts Cardiovascular Events in Incident Peritoneal Dialysis Patients

(2014) Y. Cho et al.   PERITONEAL DIALYSIS INTERNATIONAL

Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota

(2014) Y. Zhu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

IL-6 in Inflammation, Immunity, and Disease

(2014) T. Tanaka et al.   Cold Spring Harbor Perspectives in Biology

Mortality in chronic kidney disease and renal replacement therapy: a population-based cohort study

(2014) Martin Neovius et al.   BMJ Open

Binding Affinity and Capacity for the Uremic Toxin Indoxyl Sulfate

(2014) Eric Devine et al.   Toxins

Indoxyl Sulfate Enhances p53-TGF-�1-Smad3 Pathway in Proximal Tubular Cells

(2013) Hidehisa Shimizu et al.   AMERICAN JOURNAL OF NEPHROLOGY

Evaluation and Management of Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline

(2013) Paul E. Stevens   ANNALS OF INTERNAL MEDICINE

Glycine conjugation: importance in metabolism, the role of glycine N-acyltransferase, and factors that influence interindividual variation

(2013) Christoffel Petrus Stephanus Badenhorst et al.   Expert Opinion on Drug Metabolism & Toxicology

TNF-α signalling and inflammation: interactions between old acquaintances

(2013) Hana Zelová et al.   INFLAMMATION RESEARCH

Meldonium decreases the diet-increased plasma levels of trimethylamine N-oxide, a metabolite associated with atherosclerosis

(2013) Maija Dambrova et al.   JOURNAL OF CLINICAL PHARMACOLOGY

p -Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase

(2013) Hiroshi Watanabe et al.   KIDNEY INTERNATIONAL

Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention

(2013) Ron T Gansevoort et al.   LANCET

Management of cardiovascular disease in patients with kidney disease

(2013) Mark R. Kahn et al.   Nature Reviews Cardiology

A Comprehensive Insight into Binding of Hippuric Acid to Human Serum Albumin: A Study to Uncover Its Impaired Elimination through Hemodialysis

(2013) Nida Zaidi et al.   PLoS One

Role of Urea in Intestinal Barrier Dysfunction and Disruption of Epithelial Tight Junction in Chronic Kidney Disease

(2012) Nosratola D. Vaziri et al.   AMERICAN JOURNAL OF NEPHROLOGY

Fibroblast Growth Factor 23 and Inflammation in CKD

(2012) J. Munoz Mendoza et al.   Clinical Journal of the American Society of Nephrology

Fibroblast growth factor-23 and interleukin-6 are risk factors for left ventricular hypertrophy in peritoneal dialysis patients

(2012) Wei-hua Liu et al.   Journal of Cardiovascular Medicine

Normal and Pathologic Concentrations of Uremic Toxins

(2012) F. Duranton et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation

(2012) Chiao-Yin Sun et al.   KIDNEY INTERNATIONAL

Indoxyl sulfate upregulates renal expression of MCP-1 via production of ROS and activation of NF-κB, p53, ERK, and JNK in proximal tubular cells

(2012) Hidehisa Shimizu et al.   LIFE SCIENCES

Uremic Toxins Induce Kidney Fibrosis by Activating Intrarenal Renin–Angiotensin–Aldosterone System Associated Epithelial-to-Mesenchymal Transition

(2012) Chiao-Yin Sun et al.   PLoS One

Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme

(2012) S. Craciun et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Intraindividual Interleukin-6 Variations on the Cardiovascular Prognosis of Patients with Chronic Renal Disease

(2012) Marian Goicoechea et al.   RENAL FAILURE

Indoxyl Sulfate Downregulates Renal Expression of Klotho through Production of ROS and Activation of Nuclear Factor-ĸB

(2011) Hidehisa Shimizu et al.   AMERICAN JOURNAL OF NEPHROLOGY

NF-κB plays an important role in indoxyl sulfate-induced cellular senescence, fibrotic gene expression, and inhibition of proliferation in proximal tubular cells

(2011) Hidehisa Shimizu et al.   AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY

Carotid Intima-Media Thickness in Psoriatic Arthritis

(2011) Matteo Nicola Dario Di Minno et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Klotho Depletion Contributes to Increased Inflammation in Kidney of the db/db Mouse Model of Diabetes via RelA (Serine)536 Phosphorylation

(2011) Y. Zhao et al.   DIABETES

Interleukin 6 Underlies Angiotensin II–Induced Hypertension and Chronic Renal Damage

(2011) Weiru Zhang et al.   HYPERTENSION

FGF23 induces left ventricular hypertrophy

(2011) Christian Faul et al.   JOURNAL OF CLINICAL INVESTIGATION

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

(2011) Zeneng Wang et al.   NATURE

Oral activated charcoal adsorbent (AST-120) ameliorates extent and instability of atherosclerosis accelerated by kidney disease in apolipoprotein E-deficient mice

(2011) Suguru Yamamoto et al.   NEPHROLOGY DIALYSIS TRANSPLANTATION

Organic anion transporters play an important role in the uptake of p-cresyl sulfate, a uremic toxin, in the kidney

(2011) Y. Miyamoto et al.   NEPHROLOGY DIALYSIS TRANSPLANTATION

Plasma cytokines, glomerular filtration rate and adipose tissue cytokines gene expression in chronic kidney disease (CKD) patients

(2011) B. Spoto et al.   NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES

Indoxyl Sulfate Upregulates Expression of ICAM-1 and MCP-1 by Oxidative Stress-Induced NF-ĸB Activation

(2010) Zohra Tumur et al.   AMERICAN JOURNAL OF NEPHROLOGY

Aldosterone blockade in chronic kidney disease: can it improve outcome?

(2010) Robert D Toto   CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION

Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes?

(2010) S. Lekawanvijit et al.   EUROPEAN HEART JOURNAL

Indoxyl Sulfate Induces Leukocyte-Endothelial Interactions through Up-regulation of E-selectin

(2010) Shunsuke Ito et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Asymmetric dimethylarginine (ADMA) induces chronic kidney disease through a mechanism involving collagen and TGF-β1 synthesis

(2010) Fabrice Mihout et al.   JOURNAL OF PATHOLOGY

The Uremic Retention Solute p-Cresyl Sulfate and Markers of Endothelial Damage

(2009) Björn K.I. Meijers et al.   AMERICAN JOURNAL OF KIDNEY DISEASES

Indoxyl Sulfate Inhibits Nitric Oxide Production and Cell Viability by Inducing Oxidative Stress in Vascular Endothelial Cells

(2009) Zohra Tumur et al.   AMERICAN JOURNAL OF NEPHROLOGY

Vascular Endothelial-Specific Dimethylarginine Dimethylaminohydrolase-1–Deficient Mice Reveal That Vascular Endothelium Plays an Important Role in Removing Asymmetric Dimethylarginine

(2009) Xinli Hu et al.   CIRCULATION

Role for TNF in atherosclerosis? Lessons from autoimmune disease

(2009) Gayle E. McKellar et al.   Nature Reviews Cardiology

Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells

(2009) G. Muteliefu et al.   NEPHROLOGY DIALYSIS TRANSPLANTATION

ADMA Impairs Nitric Oxide–Mediated Arteriolar Function Due to Increased Superoxide Production by Angiotensin II–NAD(P)H Oxidase Pathway

(2008) Zoltan Veresh et al.   HYPERTENSION

Does FGF23 toxicity influence the outcome of chronic kidney disease?

(2008) M. S. Razzaque   NEPHROLOGY DIALYSIS TRANSPLANTATION

Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats

(2008) A. Adijiang et al.   NEPHROLOGY DIALYSIS TRANSPLANTATION