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Toxins
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Toxicity of Uremic Compounds: Recent Research & Development
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Toxicity of Uremic Compounds: Recent Research & Development

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Uremic Toxins".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 11690

Special Issue Editors

Dr. Marcela Sorelli

E-Mail Website
Guest Editor
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil
Interests: cardiovascular diseases; renal diseases; inflammation; uremic toxins; immune system; cardiorenal syndrome
Dr. Andréa Emilia Marques Stinghen

E-Mail Website
Guest Editor
Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, Brazil
Interests: uremic toxins; chronic kidney diseases; endothelial dysfunction; dialysis; peritoneal dialysate

Special Issue Information

Dear Colleagues,

Research in the field of uremic toxins has grown significantly over the past few decades. Uremic compounds are a group of molecules that accumulate in the bloodstream when the kidneys are unable to effectively remove them from the body. Uremia, a condition where the kidneys fail to filter waste products from the blood, can lead to the accumulation of various toxins in the body. These toxins have been linked to several adverse health outcomes, including cardiovascular disease, neurological disorders, and even death. Therefore, identifying and characterizing uremic toxins is crucial for developing targeted therapies that can improve the quality of life and survival rates of patients with kidney disease. There are some important areas related to this topic, such as the role of gut microbiota in uremic toxicity, identifying new biomarkers for uremic toxicity, as well as the development of more effective dialysis treatments that can remove uremic compounds from the blood. Novel therapeutic approaches, such as the use of enzymes to break down toxic molecules, are also being explored. Researchers have used advanced techniques such as metabolomics and proteomics to study the structure, function, and effects of uremic toxins, providing a deeper understanding of their role in disease pathogenesis. With ongoing research, the hope is that more effective treatments and preventative measures can be developed to improve the lives of those with kidney disease. 

Dr. Marcela Sorelli
Dr. Andréa Emilia Marques Stinghen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • uremic toxins
  • uremia
  • kidney diseases
  • dialysis
  • cardiovascular diseases
  • omics

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Published Papers (5 papers)

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Research

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14 pages, 12481 KiB  
Article
The Role of α3β1 Integrin Modulation on Fabry Disease Podocyte Injury and Kidney Impairment
by Bruna Bosquetti, Aline Aparecida Santana, Paulo Cézar Gregório, Regiane Stafim da Cunha, Guilherme Miniskiskosky, Julia Budag, Célia Regina Cavichiolo Franco, Edneia Amancio de Souza Ramos, Fellype Carvalho Barreto and Andréa Emilia Marques Stinghen
Toxins 2023, 15(12), 700; https://doi.org/10.3390/toxins15120700 - 14 Dec 2023
Viewed by 1711
Abstract
Podocyte dysfunction plays a crucial role in renal injury and is identified as a key contributor to proteinuria in Fabry disease (FD), primarily impacting glomerular filtration function (GFF). The α3β1 integrins are important for podocyte adhesion to the glomerular basement membrane, and disturbances [...] Read more.
Podocyte dysfunction plays a crucial role in renal injury and is identified as a key contributor to proteinuria in Fabry disease (FD), primarily impacting glomerular filtration function (GFF). The α3β1 integrins are important for podocyte adhesion to the glomerular basement membrane, and disturbances in these integrins can lead to podocyte injury. Therefore, this study aimed to assess the effects of chloroquine (CQ) on podocytes, as this drug can be used to obtain an in vitro condition analogous to the FD. Murine podocytes were employed in our experiments. The results revealed a dose-dependent reduction in cell viability. CQ at a sub-lethal concentration (1.0 µg/mL) induced lysosomal accumulation significantly (p < 0.0001). Morphological changes were evident through scanning electron microscopy and immunofluorescence, highlighting alterations in F-actin and nucleus morphology. No significant changes were observed in the gene expression of α3β1 integrins via RT-qPCR. Protein expression of α3 integrin was evaluated with Western Blotting and immunofluorescence, demonstrating its lower detection in podocytes exposed to CQ. Our findings propose a novel in vitro model for exploring secondary Fabry nephropathy, indicating a modulation of α3β1 integrin and morphological alterations in podocytes under the influence of CQ. Full article
(This article belongs to the Special Issue Toxicity of Uremic Compounds: Recent Research & Development)
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8 pages, 287 KiB  
Communication
Association between Dental Scores and Saliva Uremic Toxins
by Claire Rigothier, Sylvain Catros, Antoine Bénard, Johan Samot, Olivier Quintin, Christian Combe, Islam Larabi, Ziad Massy and Jean-Claude Alvarez
Toxins 2023, 15(11), 666; https://doi.org/10.3390/toxins15110666 - 20 Nov 2023
Cited by 1 | Viewed by 1815
Abstract
Dental health is frequently altered in patients with chronic kidney disease. We conducted a prospective study on dental health in CKD patients with a specific interest in the association between dental health issues and the accumulation of uremic toxins in the saliva. A [...] Read more.
Dental health is frequently altered in patients with chronic kidney disease. We conducted a prospective study on dental health in CKD patients with a specific interest in the association between dental health issues and the accumulation of uremic toxins in the saliva. A total of 88 patients were included in the study, with chronic kidney disease stage 2 to 5 (without kidney replacement). We analysed the total concentrations of eight uremic toxins (trimethylamine N-oxide -TMAO-, Indoxyl Sulfate, P-cresyl-sulfate, Indole 3-acetic acid, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid -CMPF-, Kynurenine, Hippuric acid and Phenylacetylglutamine) and three precursors of uremic toxins (Tyrosine, Phenylalanine and Tryptophan) in the saliva using LC-MS/MS. We observed, for the first time, the association between various dental scores: DMFT, FST, CPITN, and OHIS, and saliva uremic toxins and precursors: TMAO, indoxyl sulfate, or hippuric acid. Further prospective interventional studies are required to confirm our results. Full article
(This article belongs to the Special Issue Toxicity of Uremic Compounds: Recent Research & Development)
15 pages, 2212 KiB  
Article
Renocardiac Effects of p-Cresyl Sulfate Administration in Acute Kidney Injury Induced by Unilateral Ischemia and Reperfusion Injury In Vivo
by Carlos Alexandre Falconi, Fernanda Fogaça-Ruiz, Jéssica Verônica da Silva, Raquel Silva Neres-Santos, Carmen Lucía Sanz, Lia Sumie Nakao, Andréa Emília Marques Stinghen, Carolina Victoria Cruz Junho and Marcela Sorelli Carneiro-Ramos
Toxins 2023, 15(11), 649; https://doi.org/10.3390/toxins15110649 - 10 Nov 2023
Viewed by 1880
Abstract
The precise mechanisms underlying the cardiovascular complications due to acute kidney injury (AKI) and the retention of uremic toxins like p-cresyl sulfate (PCS) remain incompletely understood. The objective of this study was to evaluate the renocardiac effects of PCS administration in animals subjected [...] Read more.
The precise mechanisms underlying the cardiovascular complications due to acute kidney injury (AKI) and the retention of uremic toxins like p-cresyl sulfate (PCS) remain incompletely understood. The objective of this study was to evaluate the renocardiac effects of PCS administration in animals subjected to AKI induced by ischemia and reperfusion (IR) injury. C57BL6 mice were subjected to distinct protocols: (i) administration with PCS (20, 40, or 60 mg/L/day) for 15 days and (ii) AKI due to unilateral IR injury associated with PCS administration for 15 days. The 20 mg/L dose of PCS led to a decrease in renal mass, an increase in the gene expression of Cystatin C and kidney injury molecule 1 (KIM-1), and a decrease in the α-actin in the heart. During AKI, PCS increased the renal injury biomarkers compared to control; however, it did not exacerbate these markers. Furthermore, PCS did not enhance the cardiac hypertrophy observed after 15 days of IR. An increase, but not potentialized, in the cardiac levels of interleukin (IL)-1β and IL-6 in the IR group treated with PCS, as well as in the injured kidney, was also noticed. In short, PCS administration did not intensify kidney injury, inflammation, and cardiac outcomes after AKI. Full article
(This article belongs to the Special Issue Toxicity of Uremic Compounds: Recent Research & Development)
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10 pages, 583 KiB  
Article
Serum Trimethylamine N-Oxide Level Is Positively Associated with Aortic Stiffness Measured by Carotid–Femoral Pulse Wave Velocity in Patients Undergoing Maintenance Hemodialysis
by Po-Yu Huang, Bang-Gee Hsu, Yu-Hsien Lai, Chih-Hsien Wang and Jen-Pi Tsai
Toxins 2023, 15(9), 572; https://doi.org/10.3390/toxins15090572 - 17 Sep 2023
Cited by 3 | Viewed by 1679
Abstract
Trimethylamine N-oxide (TMAO) is a biomarker that is effective in predicting major adverse cardiovascular (CV) events. Age-related vascular problems are significantly affected by aortic stiffness (AS), which is independently linked to CV morbidity and mortality. This study aimed to determine the association [...] Read more.
Trimethylamine N-oxide (TMAO) is a biomarker that is effective in predicting major adverse cardiovascular (CV) events. Age-related vascular problems are significantly affected by aortic stiffness (AS), which is independently linked to CV morbidity and mortality. This study aimed to determine the association between serum TMAO levels and carotid–femoral pulse wave velocity (cfPWV) in patients receiving hemodialysis (HD) therapy. In total, 115 patients with HD were enrolled in this study. The AS group included patients whose cfPWV was >10 m/s. Using high-performance liquid chromatography and mass spectrometry, the levels of serum TMAO were measured. The AS group included 42 (36.5%) patients, and compared with the non-AS group, the rates of diabetes, hypertension, older age, systolic blood pressure, serum glucose, and TMAO levels were high. In the multivariate logistic regression analysis, serum TMAO and age were independently linked with AS after correcting for the factors significantly associated with AS. Following multivariate stepwise linear regression analysis, serum TMAO in these individuals was found to be strongly correlated with cfPWV values (p < 0.001). In patients on chronic HD, serum TMAO level is an independent measure of AS and strongly correlated with cfPWV. Full article
(This article belongs to the Special Issue Toxicity of Uremic Compounds: Recent Research & Development)
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Review

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22 pages, 1476 KiB  
Review
Unveiling the Clinical Benefits of High-Volume Hemodiafiltration: Optimizing the Removal of Medium-Weight Uremic Toxins and Beyond
by Cristian Pedreros-Rosales, Aquiles Jara, Eduardo Lorca, Sergio Mezzano, Roberto Pecoits-Filho and Patricia Herrera
Toxins 2023, 15(9), 531; https://doi.org/10.3390/toxins15090531 - 29 Aug 2023
Cited by 6 | Viewed by 3923
Abstract
Dialysis treatment has improved the survival of patients with kidney failure. However, the hospitalization and mortality rates remain alarmingly high, primarily due to incomplete uremic toxin elimination. High-volume hemodiafiltration (HDF) has emerged as a promising approach that significantly improves patient outcomes by effectively [...] Read more.
Dialysis treatment has improved the survival of patients with kidney failure. However, the hospitalization and mortality rates remain alarmingly high, primarily due to incomplete uremic toxin elimination. High-volume hemodiafiltration (HDF) has emerged as a promising approach that significantly improves patient outcomes by effectively eliminating medium and large uremic toxins, which explains its increasing adoption, particularly in Europe and Japan. Interest in this therapy has grown following the findings of the recently published CONVINCE study, as well as the need to understand the mechanisms behind the benefits. This comprehensive review aims to enhance the scientific understanding by explaining the underlying physiological mechanisms that contribute to the positive effects of HDF in terms of short-term benefits, like hemodynamic tolerance and cardiovascular disease. Additionally, it explores the rationale behind the medium-term clinical benefits, including phosphorus removal, the modulation of inflammation and oxidative stress, anemia management, immune response modulation, nutritional effects, the mitigation of bone disorders, neuropathy relief, and amyloidosis reduction. This review also analyzes the impact of HDF on patient-reported outcomes and mortality. Considering the importance of applying personalized uremic toxin removal strategies tailored to the unique needs of each patient, high-volume HDF appears to be the most effective treatment to date for patients with renal failure. This justifies the need to prioritize its application in clinical practice, initially focusing on the groups with the greatest potential benefits and subsequently extending its use to a larger number of patients. Full article
(This article belongs to the Special Issue Toxicity of Uremic Compounds: Recent Research & Development)
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