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American Journal of Physiology. Renal... Jun 2019The gut microbiome is composed of a diverse population of bacteria that have beneficial and adverse effects on human health. The microbiome has recently gained attention... (Review)
Review
The gut microbiome is composed of a diverse population of bacteria that have beneficial and adverse effects on human health. The microbiome has recently gained attention and is increasingly noted to play a significant role in health and a number of disease states. Increasing urea concentration during chronic kidney disease (CKD) leads to alterations in the intestinal flora that can increase production of gut-derived toxins and alter the intestinal epithelial barrier. These changes can lead to an acceleration of the process of kidney injury. A number of strategies have been proposed to interrupt this pathway of injury in CKD. The purpose of this review is to summarize the role of the gut microbiome in CKD, tools used to study this microbial population, and attempts to alter its composition for therapeutic purposes.
Topics: Animals; Bacteria; Dietary Supplements; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Intestinal Mucosa; Intestines; Kidney; Permeability; Renal Insufficiency, Chronic; Urea; Uremia
PubMed: 30864840
DOI: 10.1152/ajprenal.00298.2018 -
Toxins Mar 2021Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of... (Review)
Review
Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an "imbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota". The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD.
Topics: Animals; Bacteria; Dietary Supplements; Disease Progression; Dysbiosis; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Intestines; Renal Dialysis; Renal Insufficiency, Chronic; Toxins, Biological; Uremia
PubMed: 33807343
DOI: 10.3390/toxins13040252 -
Nature Reviews. Nephrology May 2019Uraemic syndrome (also known as uremic syndrome) in patients with advanced chronic kidney disease involves the accumulation in plasma of small-molecule uraemic solutes... (Review)
Review
Uraemic syndrome (also known as uremic syndrome) in patients with advanced chronic kidney disease involves the accumulation in plasma of small-molecule uraemic solutes and uraemic toxins (also known as uremic toxins), dysfunction of multiple organs and dysbiosis of the gut microbiota. As such, uraemic syndrome can be viewed as a disease of perturbed inter-organ and inter-organism (host-microbiota) communication. Multiple biological pathways are affected, including those controlled by solute carrier (SLC) and ATP-binding cassette (ABC) transporters and drug-metabolizing enzymes, many of which are also involved in drug absorption, distribution, metabolism and elimination (ADME). The remote sensing and signalling hypothesis identifies SLC and ABC transporter-mediated communication between organs and/or between the host and gut microbiota as key to the homeostasis of metabolites, antioxidants, signalling molecules, microbiota-derived products and dietary components in body tissues and fluid compartments. Thus, this hypothesis provides a useful perspective on the pathobiology of uraemic syndrome. Pathways considered central to drug ADME might be particularly important for the body's attempts to restore homeostasis, including the correction of disturbances due to kidney injury and the accumulation of uraemic solutes and toxins. This Review discusses how the remote sensing and signalling hypothesis helps to provide a systems-level understanding of aspects of uraemia that could lead to novel approaches to its treatment.
Topics: Biomarkers; Host Microbial Interactions; Humans; Renal Insufficiency, Chronic; Signal Transduction; Uremia
PubMed: 30728454
DOI: 10.1038/s41581-019-0111-1 -
Clinical Cardiology Oct 2017A rising prevalence of end-stage renal disease (ESRD) has led to a rise in ESRD-related pericardial syndromes, calling for a better understanding of its pathophysiology,... (Review)
Review
A rising prevalence of end-stage renal disease (ESRD) has led to a rise in ESRD-related pericardial syndromes, calling for a better understanding of its pathophysiology, diagnoses, and management. Uremic pericarditis, the most common manifestation of uremic pericardial disease, is a contemporary problem that calls for intensive hemodialysis, anti-inflammatories, and often, drainage of large inflammatory pericardial effusions. Likewise, asymptomatic pericardial effusions can become large and impact the hemodynamics of patients on chronic hemodialysis. Constrictive pericarditis is also well documented in this population, ultimately resulting in pericardiectomy for definitive treatment. The management of pericardial diseases in ESRD patients involves internists, cardiologists, and nephrologists. Current guidelines lack clarity with respect to the management of pericardial processes in the ESRD population. Our review aims to describe the etiology, classification, clinical manifestations, diagnostic imaging tools, and treatment options of pericardial diseases in this population.
Topics: Heart; Hemodynamics; Humans; Incidence; Kidney; Kidney Failure, Chronic; Pericardial Effusion; Pericarditis, Constrictive; Prevalence; Risk Factors; Treatment Outcome; Uremia
PubMed: 28873222
DOI: 10.1002/clc.22770 -
American Journal of Kidney Diseases :... Jan 2017Maintenance dialysis patients experience a high burden of physical and emotional symptoms that directly affect their quality of life and health care utilization. In this... (Review)
Review
Maintenance dialysis patients experience a high burden of physical and emotional symptoms that directly affect their quality of life and health care utilization. In this review, we specifically highlight common troublesome symptoms affecting dialysis patients: insomnia, restless legs syndrome, and uremic pruritus. Epidemiology, pathophysiology, and evidence-based current treatment are reviewed with the goal of providing a guide for diagnosis and treatment. Finally, we identify multiple additional areas of further study needed to improve symptom management in dialysis patients.
Topics: Aged; Humans; Male; Pruritus; Renal Dialysis; Restless Legs Syndrome; Sleep Wake Disorders; Uremia
PubMed: 27693261
DOI: 10.1053/j.ajkd.2016.07.031 -
Toxins Sep 2020Chronic kidney disease (CKD) afflicts more than 500 million people worldwide and is one of the fastest growing global causes of mortality. When glomerular filtration... (Review)
Review
Chronic kidney disease (CKD) afflicts more than 500 million people worldwide and is one of the fastest growing global causes of mortality. When glomerular filtration rate begins to fall, uremic toxins accumulate in the serum and significantly increase the risk of death from cardiovascular disease and other causes. Several of the most harmful uremic toxins are produced by the gut microbiota. Furthermore, many such toxins are protein-bound and are therefore recalcitrant to removal by dialysis. We review the derivation and pathological mechanisms of gut-derived, protein-bound uremic toxins (PBUTs). We further outline the emerging relationship between kidney disease and gut dysbiosis, including the bacterial taxa altered, the regulation of microbial uremic toxin-producing genes, and their downstream physiological and neurological consequences. Finally, we discuss gut-targeted therapeutic strategies employed to reduce PBUTs. We conclude that targeting the gut microbiota is a promising approach for the treatment of CKD by blocking the serum accumulation of PBUTs that cannot be eliminated by dialysis.
Topics: Animals; Bacteria; Bacterial Toxins; Disease Progression; Dysbiosis; Gastrointestinal Microbiome; Humans; Protein Binding; Renal Dialysis; Renal Insufficiency, Chronic; Uremia
PubMed: 32932981
DOI: 10.3390/toxins12090590 -
International Journal of Molecular... Jun 2019Elucidation of molecular and cellular mechanisms of the uremic syndrome is a very challenging task. More than 130 substances are now considered to be "uremic toxins" and... (Review)
Review
Elucidation of molecular and cellular mechanisms of the uremic syndrome is a very challenging task. More than 130 substances are now considered to be "uremic toxins" and represent a very diverse group of molecules. The toxicity of these molecules affects many cellular processes, and expectably, some of them are able to disrupt mitochondrial functioning. However, mitochondria can be the source of uremic toxins as well, as the mitochondrion can be the site of complete synthesis of the toxin, whereas in some scenarios only some enzymes of the pathway of toxin synthesis are localized here. In this review, we discuss the role of mitochondria as both the target and source of pathological processes and toxic compounds during uremia. Our analysis revealed about 30 toxins closely related to mitochondria. Moreover, since mitochondria are key regulators of cellular redox homeostasis, their functioning might directly affect the production of uremic toxins, especially those that are products of oxidation or peroxidation of cellular components, such as aldehydes, advanced glycation end-products, advanced lipoxidation end-products, and reactive carbonyl species. Additionally, as a number of metabolic products can be degraded in the mitochondria, mitochondrial dysfunction would therefore be expected to cause accumulation of such toxins in the organism. Alternatively, many uremic toxins (both made with the participation of mitochondria, and originated from other sources including exogenous) are damaging to mitochondrial components, especially respiratory complexes. As a result, a positive feedback loop emerges, leading to the amplification of the accumulation of uremic solutes. Therefore, uremia leads to the appearance of mitochondria-damaging compounds, and consecutive mitochondrial damage causes a further rise of uremic toxins, whose synthesis is associated with mitochondria. All this makes mitochondrion an important player in the pathogenesis of uremia and draws attention to the possibility of reducing the pathological consequences of uremia by protecting mitochondria and reducing their role in the production of uremic toxins.
Topics: Acute Kidney Injury; Animals; Antioxidants; Humans; Mitochondria; Molecular Targeted Therapy; Oxidation-Reduction; Oxidative Stress; Renal Insufficiency, Chronic; Toxins, Biological; Urea; Uremia
PubMed: 31242575
DOI: 10.3390/ijms20123094 -
Frontiers in Immunology 2022Uremic neuropathy in children encompasses a wide range of central nervous system (CNS), peripheral nervous system (PNS), autonomic nervous system (ANS), and... (Review)
Review
Uremic neuropathy in children encompasses a wide range of central nervous system (CNS), peripheral nervous system (PNS), autonomic nervous system (ANS), and psychological abnormalities, which is associated with progressive renal dysfunction. Clinically, the diagnosis of uremic neuropathy in children is often made retrospectively when symptoms improve after dialysis or transplantation, due to there is no defining signs or laboratory and imaging findings. These neurological disorders consequently result in increased morbidity and mortality among children population, making uremia an urgent public health problem worldwide. In this review, we discuss the epidemiology, potential mechanisms, possible treatments, and the shortcomings of current research of uremic neuropathy in children. Mechanistically, the uremic neuropathy may be caused by retention of uremic solutes, increased oxidative stress, neurotransmitter imbalance, and disturbance of the blood-brain barrier (BBB). Neuroimmune, including the change of inflammatory factors and immune cells, may also play a crucial role in the progression of uremic neuropathy. Different from the invasive treatment of dialysis and kidney transplantation, intervention in neuroimmune and targeted anti-inflammatory therapy may provide a new insight for the treatment of uremia.
Topics: Child; Humans; Inflammation; Polyneuropathies; Renal Dialysis; Retrospective Studies; Uremia
PubMed: 36189322
DOI: 10.3389/fimmu.2022.1013562 -
BMJ Case Reports Oct 2019
Topics: Adult; Biomarkers; Diagnosis, Differential; Humans; Male; Renal Insufficiency; Renal Replacement Therapy; Stomatitis; Tongue Diseases; Uremia
PubMed: 31628094
DOI: 10.1136/bcr-2019-231948 -
Iranian Journal of Kidney Diseases Mar 2015Immunologically, End Stage renal Disease (ESRD) is associated with some disorders in both innate and adaptive immune system in such a form that there is a coexistence of... (Review)
Review
Immunologically, End Stage renal Disease (ESRD) is associated with some disorders in both innate and adaptive immune system in such a form that there is a coexistence of both immune activation and immune suppression. Although these disorders are complex yet thoroughly unknown, there is a close relation between the progressively defective immune system with side effects as well as mortality causes including cardiovascular problems, infections, and malignancies. From the other point, chronic inflammation as a major determinant of "dialysis syndrome" (including malnutrition, cachexia, and vasculopathy) is considered as the main factor of inability and mortality in dialysis patients. Such inflammation is generally arisen from immune system response to uremia and individual's repetitive contact with dialysis instruments and, in the long term, leads to premature aging via intensifying tissue degeneration. Therefore, the immune system is known as one of the most important therapeutic targets to reduce morbidity and mortality in uremic and dialysis patients. This review addresses different aspects as well as mechanisms of immune system dysfunction and possible therapeutics in dialysis patients.
Topics: Humans; Immune System Diseases; Kidney Failure, Chronic; Prognosis; Renal Dialysis; Treatment Outcome; Uremia
PubMed: 25851286
DOI: No ID Found