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 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 Pelacarsen for lowering lipoprotein(a): implications for patients with chronic kidney disease

2020 ◽  
Vol 13 (5) ◽  
pp. 753-757
Author(s):  
Raul Fernandez-Prado ◽  
Maria Vanessa Perez-Gomez ◽  
Alberto Ortiz
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Messenger Rna ◽  
Controlled Trial ◽  
Good News ◽  
Phase 2 ◽  
Phase 3 ◽  
Lipoprotein A ◽  
Increased Risk

Abstract Chronic kidney disease (CKD) patients are at an increased risk of cardiovascular disease (CVD) and statins may not be protective in advanced CKD. The reasons for the limited efficacy of statins in advanced CKD are unclear, but statins may increase plasma levels of the highly atherogenic molecule lipoprotein(a), also termed Lp(a), as well as PCSK9 (protein convertase subtilisin/kexin type 9) levels. Lp(a) has also been linked to calcific aortic stenosis, which is common in CKD. Moreover, circulating Lp(a) levels increase in nephrotic syndrome with declining renal function and are highest in patients on peritoneal dialysis. Thus, the recent publication of the Phase 2 randomized controlled trial of pelacarsen [also termed AKCEA-APO(a)-LRx and TQJ230], a hepatocyte-directed antisense oligonucleotide targeting the LPA gene messenger RNA, in persons with CVD should be good news for nephrologists. Pelacarsen safely and dose-dependently decreased Lp(a) levels by 35–80% and a Phase 3 trial [Lp(a)HORIZON, NCT04023552] is planned to run from 2020 to 2024. Unfortunately, patients with estimated glomerular filtration rate &lt;60 mL/min or urinary albumin:creatinine ratio &gt;100 mg/g were excluded from Phase 2 trials and those with ‘significant kidney disease’ will be excluded from the Phase 3 trial. Optimized exclusion criteria for Lp(a)HORIZON would provide insights into the role of Lp(a) in CVD in CKD patients.

P0881ANEMIA SIGNIFICANTLY INCREASES RISK OF OSTEOPOROSIS IN PATIENTS WITH NON-DIALYSIS CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Seonyeong Lee ◽  
Yooju Nam ◽  
Hyung Woo Kim ◽  
Jae Hyun Chang ◽  
Tae-Hyun Yoo
Keyword(s):  
Bone Mineral Density ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Bone Mineral ◽  
Mineral Density ◽  
Multivariable Logistic Regression Model ◽  
Chronic Anemia ◽  
Increased Risk ◽  
Anemia Group

Abstract Background and Aims Anemia was frequently observed in chronic renal failure patients. The risk of osteoporosis is higher in patients with chronic anemia. Chronic anemia also showed a close relationship with bone mineral density. However, few studies have been done whether anemia affects bone mineral density with chronic kidney disease(CKD) patient. Therefore, the aim of our study is to evaluate the relationship between anemia and bone mineral density(BMD) in a large sample of non-dialysis CKD cohort. Method We performed an observational study in 2,089 patients who measured hemoglobin and BMD with non-dialysis CKD enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Anemia was defined as hemoglobin(Hb) levels of &lt; 13.0 g/dL for males and 12.0 g/dL for females, respectively. BMD was estimated by dual energy x-ray absorptiometry system. The observed variable was decline of BMD during follow up. Results The mean age was 53.6 ± 12.2 years and 1,292(61.1%) patients were males. The BMD score was positively correlated with hemoglobin levels (β, 0.007; 95% CI, 0.003-0.012; P 0.002), but inversely with prevalence of anemia (β, -0.03; 95% CI, -0.042--0.008; P 0.004). In the multivariable logistic regression model, the prevalence of osteoporosis was significantly higher in the anemia group than that in the normal hemoglobin levels (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.11-2.51, P=0.014). Among 881 patients except unavailable following BMD, 396 (19.7%) patients developed the decline of BMD during a median follow-up duration of 48 (interquartile range, 46-49) months. In the fully adjusted multivariable Cox models, risk of developing the decline of BMD was significantly higher in the anemia group (HR, 1.38; 95% CI, 1.02-1.87; P= 0.036) as compared to normal hemoglobin group. Conclusion We found that anemia is independently and significantly correlated with an increased risk of osteoporosis with non-dialysis CKD. Our study suggests that prompt correction of anemia in CKD patients could be beneficial to preserving bone mineral density.

scholarly journals Cognitive Impairment in Chronic Kidney Disease: Vascular Milieu and the Potential Therapeutic Role of Exercise

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Ulf G. Bronas ◽  
Houry Puzantian ◽  
Mary Hannan
Keyword(s):  
Quality Of Life ◽  
Chronic Kidney Disease ◽  
Cognitive Impairment ◽  
Kidney Disease ◽  
Physical Function ◽  
Vascular Dysfunction ◽  
Therapeutic Modality ◽  
Increased Risk

Chronic kidney disease (CKD) is considered a model of accelerated aging. More specifically, CKD leads to reduced physical functioning and increased frailty, increased vascular dysfunction, vascular calcification and arterial stiffness, high levels of systemic inflammation, and oxidative stress, as well as increased cognitive impairment. Increasing evidence suggests that the cognitive impairment associated with CKD may be related to cerebral small vessel disease and overall impairment in white matter integrity. The triad of poor physical function, vascular dysfunction, and cognitive impairment places patients living with CKD at an increased risk for loss of independence, poor health-related quality of life, morbidity, and mortality. The purpose of this review is to discuss the available evidence of cerebrovascular-renal axis and its interconnection with early and accelerated cognitive impairment in patients with CKD and the plausible role of exercise as a therapeutic modality. Understanding the cerebrovascular-renal axis pathophysiological link and its interconnection with physical function is important for clinicians in order to minimize the risk of loss of independence and improve quality of life in patients with CKD.

scholarly journals Toll-Like Receptors in Acute Kidney Injury

2021 ◽  
Vol 22 (2) ◽  
pp. 816
Author(s):  
Cristina Vázquez-Carballo ◽  
Melania Guerrero-Hue ◽  
Cristina García-Caballero ◽  
Sandra Rayego-Mateos ◽  
Lucas Opazo-Ríos ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Pathological Condition ◽  
Kidney Injury ◽  
Preclinical Studies ◽  
Toll Like Receptors ◽  
Middle Income ◽  
Increased Risk

Acute kidney injury (AKI) is an important health problem, affecting 13.3 million individuals/year. It is associated with increased mortality, mainly in low- and middle-income countries, where renal replacement therapy is limited. Moreover, survivors show adverse long-term outcomes, including increased risk of developing recurrent AKI bouts, cardiovascular events, and chronic kidney disease. However, there are no specific treatments to decrease the adverse consequences of AKI. Epidemiological and preclinical studies show the pathological role of inflammation in AKI, not only at the acute phase but also in the progression to chronic kidney disease. Toll-like receptors (TLRs) are key regulators of the inflammatory response and have been associated to many cellular processes activated during AKI. For that reason, a number of anti-inflammatory agents targeting TLRs have been analyzed in preclinical studies to decrease renal damage during AKI. In this review, we updated recent knowledge about the role of TLRs, mainly TLR4, in the initiation and development of AKI as well as novel compounds targeting these molecules to diminish kidney injury associated to this pathological condition.

scholarly journals Prognostic Value of Soluble Suppression of Tumorigenicity 2 in Chronic Kidney Disease Patients: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Guangying Guo ◽  
Aoran Huang ◽  
Xin Huang ◽  
Tianhua Xu ◽  
Li Yao
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Sample Size ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Prognostic Role ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Cvd Mortality

Objective. Previous studies have controversial results about the prognostic role of soluble suppression of tumorigenicity 2 (sST2) in chronic kidney disease (CKD). Therefore, we conduct this meta-analysis to access the association between sST2 and all-cause mortality, cardiovascular disease (CVD) mortality, and CVD events in patients with CKD. Methods. The publication studies on the association of sST2 with all-cause mortality, CVD mortality, and CVD events from PubMed and Embase were searched through August 2020. We pooled the hazard ratio (HR) comparing high versus low levels of sST2 and subgroup analysis based on treatment, continent, and diabetes mellitus (DM) proportion, and sample size was also performed. Results. There were 15 eligible studies with 11,063 CKD patients that were included in our meta-analysis. Elevated level of sST2 was associated with increased risk of all-cause mortality (HR 2.05; 95% confidence interval (CI), 1.51–2.78), CVD mortality (HR 1.68; 95% CI, 1.35–2.09), total CVD events (HR 1.88; 95% CI, 1.26–2.80), and HF (HR 1.35; 95% CI, 1.11–1.64). Subgroup analysis based on continent, DM percentage, and sample size showed that these factors did not influence the prognostic role of sST2 levels to all-cause mortality. Conclusions. Our results show that high levels of sST2 could predict the all-cause mortality, CVD mortality, and CVD events in CKD patients.

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 Different Effects of Empagliflozin on Markers of Mineral-Bone Metabolism in Diabetic and Non-Diabetic Patients with Stage 3 Chronic Kidney Disease

Medicina ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 1352
Author(s):  
Anna Masajtis-Zagajewska ◽  
Tomasz Hołub ◽  
Katarzyna Pęczek ◽  
Agnieszka Makówka ◽  
Michał Nowicki
Keyword(s):  
Chronic Kidney Disease ◽  
Calcium Phosphate ◽  
Kidney Disease ◽  
Bone Metabolism ◽  
Bone Fractures ◽  
Sglt2 Inhibitor ◽  
Diabetic Patients ◽  
Mineral Density ◽  
Increased Risk ◽  
Fgf 23

Background and objectives: Treatment with sodium–glucose co-transporter 2 (SGLT2) inhibitors decrease tubular reabsorption of phosphate, which may explain the reduction of bone mineral density and an excess of bone fractures observed in some studies with this class of drugs. Since an increased risk of bone fractures may also be a result of diabetes itself, our study aimed to compare the effect of empagliflozin on the markers of mineral-bone metabolism between diabetic (DKD) and non-diabetic (ND-CKD) patients with stage 3 chronic kidney disease (CKD). Materials and Methods: Forty-two patients with stage 3 CKD and A2 albuminuria, including 18 with DKD and 24 ND-CKD, were investigated. All subjects received 10 mg empagliflozin for 7 days. Serum calcium, phosphate, parathormone (PTH), calcitriol, bone alkaline phosphatase (BAP), FGF-23 and urine calcium, phosphate, albumin and the renal tubular maximum reabsorption rate of phosphate to the glomerular filtration rate (TmP-GFR) were measured before and after empagliflozin administration. Differences in biomarkers response to empagliflozin between DKD and ND-CKD were the main measures of outcome. Results: There was a significant increase of PTH, FGF-23 and phosphate in DKD but not in ND-CKD whereas BAP and TmP/GFR did not change in either group. The reduction of albuminuria was only significant in ND-CKD. Conclusions: The effect of SGLT2 inhibitor on serum mineral and bone markers and on albuminuria in patients with CKD may be differently modified by the presence of diabetes mellitus.

scholarly journals Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Siti Maryam Ahmad Kendong ◽  
Raja Affendi Raja Ali ◽  
Khairul Najmi Muhammad Nawawi ◽  
Hajar Fauzan Ahmad ◽  
Norfilza Mohd Mokhtar
Keyword(s):  
Colorectal Cancer ◽  
Environmental Factors ◽  
Gut Microbiota ◽  
Early Onset ◽  
Early Stage ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Gut Dysbiosis ◽  
Early Onset Colorectal Cancer

Colorectal cancer (CRC) is a heterogeneous disease that commonly affects individuals aged more than 50 years old globally. Regular colorectal screening, which is recommended for individuals aged 50 and above, has decreased the number of cancer death toll over the years. However, CRC incidence has increased among younger population (below 50 years old). Environmental factors, such as smoking, dietary factor, urbanization, sedentary lifestyle, and obesity, may contribute to the rising trend of early-onset colorectal cancer (EOCRC) because of the lack of genetic susceptibility. Research has focused on the role of gut microbiota and its interaction with epithelial barrier genes in sporadic CRC. Population with increased consumption of grain and vegetables showed high abundance of Prevotella, which reduces the risk of CRC. Microbes, such as Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli deteriorate in the intestinal barrier, which leads to the infiltration of inflammatory mediators and chemokines. Gut dysbiosis may also occur following inflammation as clearly observed in animal model. Both gut dysbiosis pre- or post-inflammatory process may cause major alteration in the morphology and functional properties of the gut tissue and explain the pathological outcome of EOCRC. The precise mechanism of disease progression from an early stage until cancer establishment is not fully understood. We hypothesized that gut dysbiosis, which may be influenced by environmental factors, may induce changes in the genome, metabolome, and immunome that could destruct the intestinal barrier function. Also, the possible underlying inflammation may give impact microbial community leading to disruption of physical and functional role of intestinal barrier. This review explains the potential role of the interaction among host factors, gut microenvironment, and gut microbiota, which may provide an answer to EOCRC.

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