scholarly journals The Aryl Hydrocarbon Receptor in Chronic Kidney Disease: Friend or Foe?

2020 ◽  
Vol 8 ◽  
Author(s):  
Yenan Mo ◽  
Zhaoyu Lu ◽  
Lixin Wang ◽  
Chunlan Ji ◽  
Chuan Zou ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Cellular Processes ◽  
Aryl Hydrocarbon

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that promotes cell responses to small molecules derived from the diet, microorganisms, metabolism and pollutants. The AhR signal regulates many basic cellular processes, including cell cycle progression, adhesion, migration, apoptosis and cell proliferation. Many studies have shown that AhR is associated with chronic kidney disease (CKD) and its complications. This article reviews the current knowledge about the role of AhR in CKD, showing that AhR mediates CKD complications, including cardiovascular disease, anemia, bone disorders, cognitive dysfunction and malnutrition, and that it influences drug metabolism in individuals with CKD. AhR enhances the intestinal barrier function to reduce the harmful effects of uremic toxins. Therefore, understanding the complex roles of AhR during CKD is important to be able to target this transcription factor safely and effectively for CKD prevention and treatment.

scholarly journals Identification of endogenous 1‐aminopyrene as a novel mediator of progressive chronic kidney disease via aryl hydrocarbon receptor activation

2020 ◽  
Vol 177 (15) ◽  
pp. 3415-3435 ◽  
Author(s):  
Hua Miao ◽  
Gang Cao ◽  
Xia‐Qing Wu ◽  
Yuan‐Yuan Chen ◽  
Dan‐Qian Chen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Receptor Activation ◽  
Aryl Hydrocarbon

scholarly journals The Role of Gut Dysbiosis in the Bone–Vascular Axis in Chronic Kidney Disease

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 285 ◽  
Author(s):  
Pieter Evenepoel ◽  
Sander Dejongh ◽  
Kristin Verbeke ◽  
Bjorn Meijers
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Mineral Density ◽  
Bone Mineral Density Loss ◽  
Gut Dysbiosis ◽  
Increased Risk ◽  
Fermentation Pattern

Patients with chronic kidney disease (CKD) are at increased risk of bone mineral density loss and vascular calcification. Bone demineralization and vascular mineralization often concur in CKD, similar to what observed in the general population. This contradictory association is commonly referred to as the ‘calcification paradox’ or the bone–vascular axis. Mounting evidence indicates that CKD-associated gut dysbiosis may be involved in the pathogenesis of the bone–vascular axis. A disrupted intestinal barrier function, a metabolic shift from a predominant saccharolytic to a proteolytic fermentation pattern, and a decreased generation of vitamin K may, alone or in concert, drive a vascular and skeletal pathobiology in CKD patients. A better understanding of the role of gut dysbiosis in the bone–vascular axis may open avenues for novel therapeutics, including nutriceuticals.

scholarly journals Aryl Hydrocarbon Receptor Activation in Chronic Kidney Disease: Role of Uremic Toxins

Nephron ◽  
2017 ◽  
Vol 137 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Jessyca S. Brito ◽  
Natália A. Borges ◽  
Marta Esgalhado ◽  
D''Angelo C. Magliano ◽  
Christophe O. Soulage ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Receptor Activation ◽  
Uremic Toxins ◽  
Aryl Hydrocarbon

Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease

2018 ◽  
Vol 93 (4) ◽  
pp. 986-999 ◽  
Author(s):  
Laetitia Dou ◽  
Stéphane Poitevin ◽  
Marion Sallée ◽  
Tawfik Addi ◽  
Bertrand Gondouin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Aryl Hydrocarbon

scholarly journals Aryl hydrocarbon receptor (AhR) and its endogenous agonist – indoxyl sulfate in chronic kidney disease

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Tomasz Kamiński ◽  
Małgorzata Michałowska ◽  
Dariusz Pawlak
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Biological Effects ◽  
P53 Protein ◽  
Free Fraction ◽  
High Reactivity ◽  
Indoxyl Sulfate ◽  
Aryl Hydrocarbon ◽  
Tryptophan Degradation

The indoxyl sulfate (IS, indoxyl sulphate) is the end product of dietary tryptophan degradation by indole pathway and significantly higher serum and tissue concentrations of this compound is observed in patients with impaired renal function. Despite the high albumin binding affinity, the remaining free fraction of IS has a number of biological effects related to the generation of oxidative stress andactivation of signaling pathways related to NF-кB, p53 protein, STAT3, TGF-β and Smad2/3. IS induces the inflammatory process, exerts nephrotoxic activity and is also a factor impairing the cardiovascular system.Its high concentrations are associated with the occurrence of cardiovascular incidents, whose frequency is significantly higher in patients with chronic kidney disease. Evaluation of the mechanisms that underlie the high reactivity of indoxyl sulfate and its biological effects showed that this compound is an agonist of the aryl hydrocarbon receptor (AhR). This receptor plays an important role in maintaining homeostasis Moreover, AhR exerts high transcriptional activity, so ligands of obciążethis receptor may exert different biological effects. The following paper describes the role of indoxyl sulfate as AhR ligand in the context of the excessive accumulation, which appears as one of the symptoms associated with chronic kidney disease.

scholarly journals Maternal Tryptophan Supplementation Protects Adult Rat Offspring against Hypertension Programmed by Maternal Chronic Kidney Disease: Implication of Tryptophan-Metabolizing Microbiome and Aryl Hydrocarbon Receptor

2020 ◽  
Vol 21 (12) ◽  
pp. 4552 ◽  
Author(s):  
Chien-Ning Hsu ◽  
I-Chun Lin ◽  
Hong-Ren Yu ◽  
Li-Tung Huang ◽  
Mao-Meng Tiao ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Aryl Hydrocarbon Receptor ◽  
Female Rats ◽  
Adult Offspring ◽  
Sprague Dawley ◽  
Aryl Hydrocarbon ◽  
Induced Hypertension ◽  
In Pregnancy

Hypertension and chronic kidney disease (CKD) can originate during early-life. Tryptophan metabolites generated by different pathways have both detrimental and beneficial effects. In CKD, uremic toxins from the tryptophan-generating metabolites are endogenous ligands of the aryl hydrocarbon receptor (AHR). The interplay between AHR, nitric oxide (NO), the renin–angiotensin system (RAS), and gut microbiota is involved in the development of hypertension. We examined whether tryptophan supplementation in pregnancy can prevent hypertension and kidney disease programmed by maternal CKD in adult offspring via the aforementioned mechanisms. Sprague–Dawley (SD) female rats received regular chow or chow supplemented with 0.5% adenine for 3 weeks to induce CKD before pregnancy. Pregnant controls or CKD rats received vehicle or tryptophan 200 mg/kg per day via oral gavage during pregnancy. Male offspring were divided into four groups (n = 8/group): control, CKD, tryptophan supplementation (Trp), and CKD plus tryptophan supplementation (CKDTrp). All rats were sacrificed at the age of 12 weeks. We found maternal CKD induced hypertension in adult offspring, which tryptophan supplementation prevented. Maternal CKD-induced hypertension is related to impaired NO bioavailability and non-classical RAS axis. Maternal CKD and tryptophan supplementation differentially shaped distinct gut microbiota profile in adult offspring. The protective effect of tryptophan supplementation against maternal CKD-induced programmed hypertension is relevant to alterations to several tryptophan-metabolizing microbes and AHR signaling pathway. Our findings support interplay among tryptophan-metabolizing microbiome, AHR, NO, and the RAS in hypertension of developmental origins. Furthermore, tryptophan supplementation in pregnancy could be a potential approach to prevent hypertension programmed by maternal CKD.

scholarly journals The gut–kidney–heart axis in chronic kidney disease

2019 ◽  
Vol 106 (3) ◽  
pp. 195-206 ◽  
Author(s):  
K Sumida ◽  
CP Kovesdy
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Therapeutic Potential ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Biological Properties ◽  
Intestinal Barrier Function ◽  
Multiple Organs ◽  
Health And Disease

The recent explosion of scientific interest in the gut microbiota has dramatically advanced our understanding of the complex pathophysiological interactions between the gut and multiple organs in health and disease. Emerging evidence has revealed that the gut microbiota is significantly altered in patients with chronic kidney disease (CKD), along with impaired intestinal barrier function. These alterations allow translocation of various gut-derived products into the systemic circulation, contributing to the development and progression of CKD and cardiovascular disease (CVD), partly mediated by chronic inflammation. Among potentially toxic gut-derived products identifiable in the systemic circulation, bacterial endotoxin and gut metabolites (e.g., p-cresyl sulfate and trimethylamine-N-oxide) have been extensively studied for their immunostimulatory and atherogenic properties. Recent studies have also suggested similar biological properties of bacterial DNA fragments circulating in the blood of patients with CKD, even in the absence of overt infections. Despite the accumulating evidence of the gut microbiota in CKD and its therapeutic potential for CVD, the precise mechanisms for multidirectional interactions between the gut, kidney, and heart remain poorly understood. This review aims to provide recent evidence on the associations between the gut microbiota, CKD, and CVD, and summarize current understanding of the potential pathophysiological mechanisms underlying the “gut–kidney–heart” axis in CKD.

scholarly journals Intestinal Barrier Function in Chronic Kidney Disease

Toxins ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 298 ◽  
Author(s):  
Björn Meijers ◽  
Ricard Farré ◽  
Sander Dejongh ◽  
Maria Vicario ◽  
Pieter Evenepoel
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Intestinal Barrier ◽  
Multilayered Structure ◽  
Toxic Waste ◽  
Intestinal Barrier Function ◽  
Waste Products ◽  
Mucin Layer ◽  
Altered Physiology

The kidneys are key contributors to body homeostasis, by virtue of controlled excretion of excessive fluid, electrolytes, and toxic waste products. The syndrome of uremia equals the altered physiology due to irreversible loss of kidney function that is left uncorrected for, despite therapeutic intervention(s). The intestines and its microbial content are prime contributors to this syndrome. The intestinal barrier separates the self (or the so-called “milieu intérior”) from the environment. In the large intestine, the intestinal barrier keeps apart human physiology and the microbiota. The enterocytes and the extracellular mucin layer functions form a complex multilayered structure, facilitating complex bidirectional metabolic and immunological crosstalk. The current review focuses on the intestinal barrier in chronic kidney disease (CKD). Loss of kidney function results in structural and functional alterations of the intestinal barrier, contribution to the syndrome of uremia.

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