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Special Issue Information

Dear Colleagues,

Metabolic complications such as insulin resistance, dyslipidemia, or protein-energy wasting are now recognized as common features of patients with chronic kidney disease (CKD), although the underlying mechanisms remain unclear. A growing body of evidence suggests that metabolic disorders are important contributors to the morbidity and mortality of these patients.

Renal clearance is impaired in patients with CKD, resulting in the accumulation of a large range of uremic solutes often referred to as uremic toxins if they exert deleterious biological activities. Several recent studies highlighted the role of the accumulation of these uremic toxins in the development of metabolic complications in CKD.

This Special Issue will include original research articles and reviews on the role of the uremic milieu and uremic toxins in the pathogenesis of the metabolic complications of CKD. Generally speaking, this Special Issue will address all kinds of metabolic disturbances associated with uremia. These metabolic disturbances can non-exhaustively include anemia, insulin resistance, defects in insulin secretion, adipose tissue dysfunction, altered adipokine secretion, low-grade inflammation, and protein-energy wasting.

Prof. Dr. Christophe O. Soulage
Guest Editor

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Keywords

uremic toxin
uremia
insulin resistance
dyslipidemia
protein-energy wasting
metabolism
white adipose tissue

Published Papers (2 papers)

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Research

Jump to: Review

22 pages, 1276 KiB

Open AccessArticle

Gut Microbiota as a Source of Uremic Toxins

by Vasily A. Popkov, Anastasia A. Zharikova, Evgenia A. Demchenko, Nadezda V. Andrianova, Dmitry B. Zorov and Egor Y. Plotnikov

Int. J. Mol. Sci. 2022, 23(1), 483; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010483 - 01 Jan 2022

Cited by 19 | Viewed by 3264

Abstract

Uremic retention solutes are the compounds that accumulate in the blood when kidney excretory function is impaired. Some of these compounds are toxic at high concentrations and are usually known as “uremic toxins”. The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually mortality during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes increase during uremia; however, the exact origin for most of them is still debatable. There are three main sources for such compounds: exogenous ones are consumed with food, whereas endogenous ones are produced by the host metabolism or by symbiotic microbiota metabolism. In this article, we identify uremic retention solutes presumably of gut microbiota origin. We used database analysis to obtain data on the enzymatic reactions in bacteria and human organisms that potentially yield uremic retention solutes and hence to determine what toxins could be synthesized in bacteria residing in the human gut. We selected biochemical pathways resulting in uremic retention solutes synthesis related to specific bacterial strains and revealed links between toxin concentration in uremia and the proportion of different bacteria species which can synthesize the toxin. The detected bacterial species essential for the synthesis of uremic retention solutes were then verified using the Human Microbiome Project database. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of the synthesis of a particular toxin by the human metabolism. Our study presents a novel bioinformatics approach for the elucidation of the origin of both uremic retention solutes and uremic toxins and for searching for the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia. Full article

(This article belongs to the Special Issue Uremic Toxins and Metabolic Complications of Chronic Kidney Disease)

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Review

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17 pages, 930 KiB

Open AccessReview

Uremic Toxins and Frailty in Patients with Chronic Kidney Disease: A Molecular Insight

by Chia-Ter Chao and Shih-Hua Lin

Int. J. Mol. Sci. 2021, 22(12), 6270; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126270 - 10 Jun 2021

Cited by 19 | Viewed by 5338

Abstract

The accumulation of uremic toxins (UTs) is a prototypical manifestation of uremic milieu that follows renal function decline (chronic kidney disease, CKD). Frailty as a potential outcome-relevant indicator is also prevalent in CKD. The intertwined relationship between uremic toxins, including small/large solutes (phosphate, asymmetric dimethylarginine) and protein-bound ones like indoxyl sulfate (IS) and p-cresyl sulfate (pCS), and frailty pathogenesis has been documented recently. Uremic toxins were shown in vitro and in vivo to induce noxious effects on many organ systems and likely influenced frailty development through their effects on multiple preceding events and companions of frailty, such as sarcopenia/muscle wasting, cognitive impairment/cognitive frailty, osteoporosis/osteodystrophy, vascular calcification, and cardiopulmonary deconditioning. These organ-specific effects may be mediated through different molecular mechanisms or signal pathways such as peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), mitogen-activated protein kinase (MAPK) signaling, aryl hydrocarbon receptor (AhR)/nuclear factor-κB (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Runt-related transcription factor 2 (RUNX2), bone morphogenic protein 2 (BMP2), osterix, Notch signaling, autophagy effectors, microRNAs, and reactive oxygen species induction. Anecdotal clinical studies also suggest that frailty may further accelerate renal function decline, thereby augmenting the accumulation of UTs in affected individuals. Judging from these threads of evidence, management strategies aiming for uremic toxin reduction may be a promising approach for frailty amelioration in patients with CKD. Uremic toxin lowering strategies may bear the potential of improving patients’ outcomes and restoring their quality of life, through frailty attenuation. Pathogenic molecule-targeted therapeutics potentially disconnect the association between uremic toxins and frailty, additionally serving as an outcome-modifying approach in the future. Full article

(This article belongs to the Special Issue Uremic Toxins and Metabolic Complications of Chronic Kidney Disease)

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