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.

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 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 Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease

Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 809
Author(s):  
Mieke Steenbeke ◽  
Sophie Valkenburg ◽  
Tessa Gryp ◽  
Wim Van Biesen ◽  
Joris R. Delanghe ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Intestinal Barrier ◽  
Uremic Toxins ◽  
Intestinal Barrier Function ◽  
Post Translational Modifications ◽  
Gut Dysbiosis ◽  
Cardiovascular Morbidity And Mortality

Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, both risk factors for cardiovascular morbidity and mortality. The relationship between fecal metabolites and plasma concentrations of PBUTs in different stages of CKD (n = 103) was explored. Estimated GFR tends to correlate with fecal butyric acid (BA) concentrations (rs = 0.212; p = 032), which, in its turn, correlates with the abundance of SCFA-producing bacteria. Specific SCFAs correlate with concentrations of PBUT precursors in feces. Fecal levels of p-cresol correlate with its derived plasma UTs (p-cresyl sulfate: rs = 0.342, p < 0.001; p-cresyl glucuronide: rs = 0.268, p = 0.006), whereas an association was found between fecal and plasma levels of indole acetic acid (rs = 0.306; p = 0.002). Finally, the albumin symmetry factor correlates positively with eGFR (rs = 0.274; p = 0.005). The decreased abundance of SCFA-producing gut bacteria in parallel with the fecal concentration of BA and indole could compromise the intestinal barrier function in CKD. It is currently not known if this contributes to increased plasma levels of PBUTs, potentially playing a role in the PTMs of albumin. Further evaluation of SCFA-producing bacteria and SCFAs as potential targets to restore both gut dysbiosis and uremia in needed.

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 Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Guillaume Courbon ◽  
Connor Francis ◽  
Claire Gerber ◽  
Samantha Neuburg ◽  
Xueyan Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Fibroblast Growth Factor ◽  
Kidney Function ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Fibroblast Growth ◽  
Lipocalin 2

AbstractBone-produced fibroblast growth factor 23 (FGF23) increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2; LCN2 the murine homolog) is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD progression. We investigated bone FGF23 regulation by circulating LCN2. At 23 weeks, Col4a3KO mice showed impaired kidney function, increased levels of kidney and serum LCN2, increased bone and serum FGF23, anemia, and left ventricular hypertrophy (LVH). Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum FGF23. Lcn2 deletion specifically prevented FGF23 elevations in response to inflammation, but not iron deficiency or phosphate, and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone cells. These results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in CKD. LCN2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD.

scholarly journals Enteropeptidase inhibitor SCO-792 effectively prevents kidney function decline and fibrosis in a rat model of chronic kidney disease

2020 ◽  
Author(s):  
Yuko Katayama ◽  
Jun Sugama ◽  
Tomohisa Suzuki ◽  
Yoshimasa Ishimura ◽  
Akihiro Kobayashi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Therapeutic Potential ◽  
Renal Plasma Flow ◽  
Production Capacity ◽  
Therapeutic Effects ◽  
Kidney Fibrosis ◽  
Obesity And Diabetes ◽  
Gfr Decline

Abstract Background Inhibiting enteropeptidase, a gut serine protease regulating protein digestion, suppresses food intake and ameliorates obesity and diabetes in mice. However, the effects of enteropeptidase inhibition on the kidney parameters are largely unknown. Here, we evaluated the chronic effects of an enteropeptidase inhibitor, SCO-792, on kidney function, albuminuria, and kidney pathology in spontaneously hypercholesterolaemic (SHC) rats, a rat chronic kidney disease (CKD) model. Methods SCO-792, an orally available enteropeptidase inhibitor, was administered (0.03% and 0.06% (w/w) in the diet) for five weeks to 20-week-old SHC rats showing albuminuria and progressive decline in glomerular filtration rate (GFR). The effects of SCO-792 and the contribution of amino acids to these effects were evaluated. Results SCO-792 increased the faecal protein content, indicating that SCO-792 inhibited enteropeptidase in SHC rats. Chronic treatment with SCO-792 prevented GFR decline and suppressed albuminuria. Moreover, SCO-792 improved glomerulosclerosis and kidney fibrosis. Pair feeding with SCO-792 (0.06%) was less effective in preventing GFR decline, albuminuria, and renal histological damage than SCO-792 treatment, indicating the enteropeptidase-inhibition-dependent therapeutic effects of SCO-792. SCO-792 did not affect the renal plasma flow, suggesting that its effect on GFR was mediated by an improvement in filtration fraction. Moreover, SCO-792 increased hydrogen sulphide production capacity, which has a role in tissue protection. Finally, methionine and cysteine supplementation to the diet abrogated SCO-792-induced therapeutic effects on albuminuria. Conclusions SCO-792-mediated inhibition of enteropeptidase potently prevented GFR decline, albuminuria, and kidney fibrosis; hence, it may have therapeutic potential against CKD.

scholarly journals Everyday Discrimination and Kidney Function Among Older Adults: Evidence From the Health and Retirement Study

2019 ◽  
Vol 75 (3) ◽  
pp. 517-521
Author(s):  
Ryon J Cobb ◽  
Roland J Thorpe ◽  
Keith C Norris
Keyword(s):  
Older Adults ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
The United States ◽  
Health And Retirement Study ◽  
Disease Epidemiology ◽  
Lower Egfr ◽  
Everyday Discrimination ◽  
Retirement Study

Abstract Background With advancing age, there is an increase in the time of and number of experiences with psychosocial stressors that may lead to the initiation and/or progression of chronic kidney disease (CKD). Our study tests whether one type of experience, everyday discrimination, predicts kidney function among middle and older adults. Methods The data were from 10 973 respondents (ages 52–100) in the 2006/2008 Health and Retirement Study, an ongoing biennial nationally representative survey of older adults in the United States. Estimated glomerular filtration rate (eGFR) derives from the Chronic Kidney Disease Epidemiology Collaboration equation. Our indicator of everyday discrimination is drawn from self-reports from respondents. Ordinary Least Squared regression (OLS) models with robust standard errors are applied to test hypotheses regarding the link between everyday discrimination and kidney function. Results Everyday discrimination was associated with poorer kidney function among respondents in our study. Respondents with higher everyday discrimination scores had lower eGFR after adjusting for demographic characteristics (B = −1.35, p &lt; .05), and while attenuated, remained significant (B = −0.79, p &lt; .05) after further adjustments for clinical, health behavior, and socioeconomic covariates. Conclusions Our study suggests everyday discrimination is independently associated with lower eGFR. These findings highlight the importance of psychosocial factors in predicting insufficiency in kidney function among middle-aged and older adults.

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