Special Issue "Uremic Toxins"
A special issue of Toxins (ISSN 2072-6651).
Deadline for manuscript submissions: closed (30 November 2013)
Prof. Dr. Joachim Jankowski
Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik IV, Hindenburgdamm 30, 12200 Berlin, Germany
Phone: +49 30 450 525567
Fax: +49 30 450 525923
Uremia is a clinical syndrome associated with fluid, electrolyte, and hormone imbalances and metabolic abnormalities, which develop in parallel with deterioration of renal function. The term uremia, which literally means urine in the blood, was first used by Piorry to describe the clinical condition associated with renal failure .Uremia is a medical disorder characterized by excessive waste products and urea, which is a waste product of urine, in the blood. As chronic renal failure progresses, a gradual dose-dependent dysfunction of most organ systems occurs . This ultimately results in the malfunctioning of the entire body, and as symptoms become more and more prominent, survival and quality of life can only be maintained by replacing kidney function by dialysis or transplantation.
Currently, chronic renal failure as well as uremia is legitimately considered as a major public-health problem. Since only a part of chronic renal failure patients progress to uremia and on the other hand the therapy of uremia is complex and expensive, (A) identification of mediators of chronic renal failure and uremia using molecular, proteomic, metabolomic, genomic and functional genomics studies, (B) identification of the underlying mechanisms of chronic renal failure and uremia, (C) validation of biomarkers for detecting chronic renal failure patients at risk of progression and (D) development of appropriate medical responses (new drug targets and/or new treatment strategies) are of great importance both for the prognosis and early intervention of renal failure patients.
Therefore, the aim of this special issue "Uremic Toxins" is to make a contribution to the clarification of the mechanisms of uremia, and to develop new therapeutic approaches.
Prof. Dr. Joachim Jankowski
1. Piorry, P.; l'Heritier, D. Traite des Alterations du Sang; Bury & JB Bailliere: Paris, France, 1840.
2. Vanholder, R.; De Smet, R. Pathophysiologic effects of uremic retention solutes. J. Am. Soc. Nephrol. 1999, 10, 1815–1823.
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- chronic renal failure
- uremic syndrome
- retention solutes
- uremic toxins
- kidney function
- cardiovascular diseases
- glomerular filtration rate
Article: 1H NMR Spectroscopy-Based Metabolomic Assessment of Uremic Toxicity, with Toxicological Outcomes, in Male Rats Following an Acute, Mid-Life Insult from Ochratoxin A
Toxins 2011, 3(6), 504-519; doi:10.3390/toxins3060504
Received: 13 March 2011; in revised form: 19 May 2011 / Accepted: 23 May 2011 / Published: 26 May 2011| Download PDF Full-text (223 KB) | Download XML Full-text | Supplementary Files
Article: 4-Pyridone-3-carboxamide-1-β-d-ribonucleoside Triphosphate (4PyTP), a Novel NAD+ Metabolite Accumulating in Erythrocytes of Uremic Children: A Biomarker for a Toxic NAD+ Analogue in Other Tissues?
Toxins 2011, 3(6), 520-537; doi:10.3390/toxins3060520
Received: 25 March 2011; in revised form: 13 May 2011 / Accepted: 31 May 2011 / Published: 7 June 2011| Download PDF Full-text (568 KB) | Download XML Full-text
Article: Comparative 1H NMR Metabolomic Urinalysis of People Diagnosed with Balkan Endemic Nephropathy, and Healthy Subjects, in Romania and Bulgaria: A Pilot Study
Toxins 2011, 3(7), 815-833; doi:10.3390/toxins3070815
Received: 30 May 2011; in revised form: 22 June 2011 / Accepted: 28 June 2011 / Published: 4 July 2011| Download PDF Full-text (640 KB) | Download XML Full-text | Supplementary Files
Toxins 2011, 3(7), 911-919; doi:10.3390/toxins3070911
Received: 29 April 2011; in revised form: 28 June 2011 / Accepted: 5 July 2011 / Published: 20 July 2011| Download PDF Full-text (394 KB) | Download XML Full-text
Article: Do Only Small Uremic Toxins, Chromophores, Contribute to the Online Dialysis Dose Monitoring by UV Absorbance?
Toxins 2012, 4(10), 849-861; doi:10.3390/toxins4100849
Received: 30 June 2012; in revised form: 25 September 2012 / Accepted: 27 September 2012 / Published: 18 October 2012| Download PDF Full-text (768 KB) | Download XML Full-text
Toxins 2012, 4(11), 962-990; doi:10.3390/toxins4110962
Received: 6 August 2012; in revised form: 26 September 2012 / Accepted: 8 October 2012 / Published: 24 October 2012| Download PDF Full-text (301 KB) | Download XML Full-text
Article: A Metabolomic Approach to Clarifying the Effect of AST-120 on 5/6 Nephrectomized Rats by Capillary Electrophoresis with Mass Spectrometry (CE-MS)
Toxins 2012, 4(11), 1309-1322; doi:10.3390/toxins4111309
Received: 18 July 2012; in revised form: 19 September 2012 / Accepted: 26 October 2012 / Published: 14 November 2012| Download PDF Full-text (708 KB) | Download XML Full-text | Supplementary Files
Article: Effects of Decreased Vitamin D and Accumulated Uremic Toxin on Human CYP3A4 Activity in Patients with End-Stage Renal Disease
Toxins 2013, 5(8), 1475-1485; doi:10.3390/toxins5081475
Received: 28 June 2013; in revised form: 1 August 2013 / Accepted: 6 August 2013 / Published: 19 August 2013| Download PDF Full-text (278 KB) | Download XML Full-text
Review: From the Gastrointestinal Tract (GIT) to the Kidneys: Live Bacterial Cultures (Probiotics) Mediating Reductions of Uremic Toxin Levels via Free Radical Signaling
Toxins 2013, 5(11), 2042-2057; doi:10.3390/toxins5112042
Received: 2 September 2013; in revised form: 4 November 2013 / Accepted: 4 November 2013 / Published: 7 November 2013| Download PDF Full-text (253 KB) | Download XML Full-text
Article: Association between Free Light Chain Levels, and Disease Progression and Mortality in Chronic Kidney Disease
Toxins 2013, 5(11), 2058-2073; doi:10.3390/toxins5112058
Received: 24 September 2013; in revised form: 28 October 2013 / Accepted: 29 October 2013 / Published: 8 November 2013| Download PDF Full-text (326 KB) | Download XML Full-text
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Type of Paper: Review
Title: The “Dioxin-like” Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease
Authors: M. Sallée 1,2, L. Dou 1, S. Poitevin 1, C. Cerini 1, P. Brunet 1,2 and S. Burtey 1,2
Affiliations: 1 Aix Marseille Université, Inserm, EPVCT UMR_S 1076, 13005, Marseille, France; E-Mail: Laetitia.Dou@univ-amu.fr (L.D.)
2 APHM, CHU Conception, Centre de Néphrologie Dialyse Transplantation Rénale, 13005, Marseille, France
Astract : Patients with chronic kidney disease (CKD) have a higher risk of cardiovascular diseases and suffer from accelerated atherosclerosis. CKD patients are permanently exposed to uremic toxins, making them good candidates as pathogenic agents. We focus here on uremic toxins from tryptophan metabolism: indolic uremic toxins (indoxyl sulfate, indole-3 acetic acid, indoxyl-β-D-glucoronide) and uremic toxins from the kynurenine pathway (kynurenine, kynurenic acid, anthranilic acid, 3-hydroxy-kynurenine, 3-hydroxy-anthranilic acid, and quinolinic acid) because of their potential involvement in cardiovascular toxicity. Uremic toxins derived from tryptophan are endogenous ligands of the transcription factor aryl hydrocarbon receptor (AhR). AhR, also known as the dioxin receptor, interacts with various regulatory and signaling proteins, including Protein Kinases and Phosphatases and Nuclear Factor-Kappa-B. AhR activation is associated with an increase in cardiovascular disease in humans and in mice. In addition, AhR activation mediates cardiotoxicity, vascular inflammation, and a procoagulant and prooxidant phenotype of vascular cells. Uremic toxins derived from tryptophan have prooxidant, proinflammatory, procoagulant, and pro-apoptotic effects on cells involved in the cardiovascular system, and some of them are related with cardiovascular complications in CKD. We discuss here how cardiovascular effects of these uremic toxins could be mediated by AhR activation, in a “dioxin-like” effect.
Type of Paper: Article
Title: Uremic Toxicity and Neurological Disorders in Mice
Authors: Jean-Marc Chillon 1,2, François Brazier 1,2,3, Philippe Bouquet 1 and Ziad A Massy 1,4,5
Affiliations: 1 INSERM U1088, Amiens, France; E-Mail: email@example.com (J.-M.C.)
2 Université de Picardie Jules Verne, Amiens, France
3 Service de Néphrologie, CHU Amiens, Amiens, France
4 Université Paris-Ile-de_France-Ouest, Paris, Boulogne Billancourt, France
5 Service de Néphrologie, Hôpital Ambroise Paré, Paris, Boulogne Billancourt, France
Abstract: Cardiovascular disease is highly prevalent in patients with chronic renal failure (CRF) and may account for 50% of all deaths in this population. Regarding the cerebral circulation, patients with end stage renal disease (ESRD) show a 4- to 10-fold greater risk of hospitalized ischemic and hemorrhagic stroke, an increased risk of cognitive impairment and dementia and a poor long-term post-stroke prognosis compared with non-ESRD individuals. In the present study, we examined impact of uremic toxicity on behavior, recognition and severity of ischemic stroke in a well defined model of CRF in mice. Uremic toxicity in mice was associated with impaired recognition and an increased in ischemic stroke severity as shown by infarct volume. These alterations were observed after 10 and 34 weeks of CRF. In contrast, after 4 weeks of CRF recognition was not impaired in our model of uremic toxicity in mice. In conclusion, uremic toxicity induces neurological disorders in mice.
Type of Paper: Article
Title: Free Light Chains Levels in Patients at Different CKD Stages
Authors: Lucie Desjardins 1,2, Sophie Liabeuf 1,2, Aurélie Lenglet 1,2, Horst-Dieter Lemke 3, Raymond Vanholder 4, Gabriel Choukroun 1,5 and Ziad A. Massy 1,6,*
Affiliations: 1 INSERM U1088, UFR de Médecine et Pharmacie, Jules Verne University of Picardy, Amiens, France; E-Mail: Liabeuf.Sophie@chu-amiens.fr (L.D.)
2 Clinical Research Centre-Division of Clinical Pharmacology, Amiens University Hospital and the Jules Verne University of Picardy, Amiens, France
3 EXcorLab, GmbH, Obemburg, Germany
4 Nephrology Section, Department of Internal Medicine, University Hospital, Ghent, Belgium
5 Division of Nephrology, Amiens University Hospital, Amiens, France
6 Division of Nephrology, Ambroise Paré Hospital, Boulogne-Billancourt, France
* Author to whom correspondence should be addressed; E-Mail: firstname.lastname@example.org; Tel.: + 33 149 095635 or + 33 149 095639 (Secr. Mrs Szuba); Fax: + 33 149 094621.
Abstract: Background: Free light chains (FLCs) have been identified as uremic toxins. The aim of this present study was to determine the associations between FLCs levels outcomes. Methods: 141 patients at CKD stages 2-5D were included in the present study. Free FLCs evaluation was performed. Results: FLC k and l levels were found to be elevated in CKD patients. Elevated FLCs appeared to be associated with mortality. However, this association disappeared after adjustment for a propensity score. Conclusions: Our results indicate that FLCs levels are elevated in CKD patients, but their link with mortality seems dependent of other well-known factors.
Type of Paper: Article
Title: Association of Indoxyl Sulfate and p-Cresyl Sulfate with Atherosclerotic Factor in Patients on Long-Term Hemodialysis
Authors: Cheng-Jui Lin 1,4,5, Chi-Feng Pan 1,4, Chih-Kuang Chuang 5,6,7, Hsuan-Liang Liu 5, Fang-Ju Sun 2,4, Tuen-Jen Wang 3, Han-Hsiang Chen 1,4 and Chih-Jen Wu 1,4,8
Affiliations:1 Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; E-Mail: email@example.com
2 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
3 Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan
4 Mackay Medicine, Nursing and Management College, Taipei, Taiwan
5 Institute of Biotechnology, National Taipei University of Technology, Taipei, Taiwan
6 Division of Genetics and Metabolism, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
7 College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
8 Graduate Institute of Medical Science, Taipei Medical University, Taipei, Taiwan
Abstract: Background: Advanced glycation end products (AGEs), a pro-inflammatory and pro-oxidative compounds, play a critical role in endothelial dysfunction and atherosclerosis. Protein-bound uremic toxins–indoxyl sulfate (IS) and p-cresyl sulfate (PCS) have also been reported to inhibit endothelial function. Our objective was to explore the association of IS and PCS with AGEs in a hemodialysis-based cohort. Methods: This study recruited 129 stable HD patients in a single medical center. Serum levels of total and free IS, PCS and AGEs were measured concurrently. General laboratory results and patient background were also investigated. Results: The serum levels of AGEs was associated with total IS (r = 2.7, p < 0.01) not total PCS (r = 0.01, NS), free IS (r = 0.11, NS) and free PCS (r = 0.04, NS) by Pearson’s analysis. Multiple linear regression analysis showed total IS was significantly related to AGEs (β = 0.296, p < 0.01), free IS (β = 0.502, p < 0.01) and creatinine (β = 0.294, p < 0.01). Serum AGEs levels correlated significantly and positively with DM status (β = 0.250, p = 0.01) and total IS (β = 0.341, p < 0.01) concentrations by another multivariate model. Moreover, patients with DM had higher serum AGEs levels than those without DM (p < 0.01).Conclusion: These findings suggest that the serum levels of total IS were associated with AGEs levels and may participate the process of artherosclerosis.
Keywords: uremic toxin; p-cresyl sulfate; indoxyl sulfate; atherosclerosis; advanced glycation end products; hemodialysis
Type of Paper: Review
Title: Probiotics: Live Bacterial Cultures that Can Mediate a Reduction in Uremic Toxins
Authors: Luis Vitetta 1,4, Anthony W Linnane 4,5 and Glenda Gobe 2,3
Affiliations: 1 Centre for Integrative Clinical and Molecular Medicine, The University of Queensland, Brisbane, Australia; E-Mail: firstname.lastname@example.org
2 Centre for Kidney Disease Research, School of Medicine, Translational Research Institute at Princess Alexandra Hospital, The University of Queensland, Brisbane, Australia
3 Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
4 Medlab, Sydney, New South Wales, Australia
5 Monash University, Australia
Abstract: At the time of birth, humans experience, as the primary mediator, an induced pro-inflammatory flux by a fleet of bacteria that assault all mucosal surfaces as well as the skin. Thus initiating effects that eventually provide the infant with an immunological profilethat is concordant with immune tissue maturation. These effects occur beneath an emergent response sensor of immune system surveillance and antigenic tolerance capability. A systematic underestimation has been to undervalue the contribution of gastrointestinal tract (GIT) dysbiosis (a gut barrier associated abnormality) that maintains low-levelpro-inflammatory processes that contribute to chronic kidney disease (CKD) development. Gut dysbiosis provides a plausible clue as to the origin of systemic uremic loads encountered in clinical practice that may explain the epidemic of CKD. In this brief review we further build a hypothesis that posits that environmentally triggered and maintained microbiome perturbations drive dysbiosis with resultant uremia. Subtle adaptation responses by the GIT micro-bio-metabolome can be significantly influenced by probiotics with specific metabolic properties that may reduce uremic toxins in the gut. The benefit may translate to a useful clinical treatment approach for patients diagnosed with CKD.
Type of Paper: Review
Title: Uremic Toxin: New Culprit of Heart Attack in Chronic Kidney Disease Patients
Authors: Shunsuke Ito 1,2 and Masayuki Yoshida 1,*
Affiliations: 1 Life Science and Bioethics, Department of International Health Development, Tokyo Medical and Dental University, #953 M and D tower, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; E-Mail: email@example.com; Tel.: +81-3-5803-4617; Fax: +81-3-5803-4725.
2 Adsorptive Medicine Technology Center, KUREHA CORPORATION, 3-26-2, Hyakunin-cho, Shinjuku-ku, Tokyo 169-8503, Japan; E-Mail: firstname.lastname@example.org
Abstract: Chronic kidney disease (CKD) has been considered as one of major risk factors of cardiovascular diseases. Though recent great advances in pathophysiology and treatment of cardiovascular disease, this remains a major global health problem. Further it is well known that cardiovascular events rates among CKD patients are increasing even after hemodialysis, but the mechanisms of so called “cardio-renal syndrome” is not clearly understood. Recently, small-molecule uremic toxins such as indoxyl sulfate and p-cresyl sulfate have been associated with cardiovascular mortality in CKD and/or dialysis patients. The sizes of these toxins are ranging from small uncharged solutes to large protein-bound structures. Since efficacy of dialysis depend upon diffusion and convection for solute clearances, the toxicity of protein-bound toxins develops over longer periods of time when compared to that of small solutes. Basic studies including ours revealed that uremic toxin, especially indoxyl sulfate, induced vascular inflammation, endothelial dysfunction and vascular calcification. These mechanisms may explain relatively poor prognosis of CKD and dialysis patients. Herein we focused on a novel causative role of uremic in developing cardiovascular diseases from in vitro, in vivo and clinical studies.
Keywords: Uremic toxin; cardio-renal syndrome; indoxyl sulfate; p-cresyl sulfate; oral adsorbent
Last update: 5 September 2013