scholarly journals Effects of Chronic Kidney Disease and Uremic Toxins on Extracellular Vesicle Biology

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 811
Author(s):  
Linda Yaker ◽  
Saïd Kamel ◽  
Jérôme Ausseil ◽  
Agnès Boullier
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
Uremic Toxins ◽  
Matrix Gla Protein ◽  
Patients With Diabetes ◽  
Calcification Inhibitors ◽  
The Impact

Vascular calcification (VC) is a cardiovascular complication associated with a high mortality rate, especially in patients with diabetes, atherosclerosis or chronic kidney disease (CKD). In CKD patients, VC is associated with the accumulation of uremic toxins, such as indoxyl sulphate or inorganic phosphate, which can have a major impact in vascular remodeling. During VC, vascular smooth muscle cells (VSMCs) undergo an osteogenic switch and secrete extracellular vesicles (EVs) that are heterogeneous in terms of their origin and composition. Under physiological conditions, EVs are involved in cell-cell communication and the maintenance of cellular homeostasis. They contain high levels of calcification inhibitors, such as fetuin-A and matrix Gla protein. Under pathological conditions (and particularly in the presence of uremic toxins), the secreted EVs acquire a pro-calcifying profile and thereby act as nucleating foci for the crystallization of hydroxyapatite and the propagation of calcification. Here, we review the most recent findings on the EVs’ pathophysiological role in VC, the impact of uremic toxins on EV biogenesis and functions, the use of EVs as diagnostic biomarkers and the EVs’ therapeutic potential in CKD.

scholarly journals Low Magnesium Exacerbates Osteoporosis in Chronic Kidney Disease Patients with Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jui-Hua Huang ◽  
Fu-Chou Cheng ◽  
Hsu-Chen Wu
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Bone Mineral ◽  
Mineral Metabolism ◽  
Inverse Correlation ◽  
Mineral Density ◽  
Lower Serum ◽  
Patients With Diabetes ◽  
The Impact ◽  
Low Serum

The aim of this study is to investigate the impact of serum Mg on bone mineral metabolism in chronic kidney disease (CKD) patients with or without diabetes. A total of 56 CKD patients not receiving dialysis were recruited and divided into two groups, one group of 27 CKD patients with diabetes and another group of 29 CKD patients without diabetes. Biochemical determinations were made, and the estimated glomerular filtration rate (eGFR) was measured. Bone mineral density was measured by dual-energy X-ray absorptiometry. Serum Mg was inversely correlated with serum CaP=0.023and positively correlated with serum parathyroid hormone (PTH)P=0.020, alkaline phosphataseP=0.044, and phosphateP=0.040in the CKD patients with diabetes. The CKD patients with diabetes had lower serum albumin and a higher proportion of hypomagnesemia and osteoporosis than the nondiabetic patients didP<0.05. Serum Mg was inversely correlated with eGFR in the CKD patients with or without diabetesP<0.05. Serum Mg showed an inverse correlation with 25-hydroxyvitamin D in CKD patients without diabetesP=0.006. Furthermore, the diabetic CKD patients with low serum Mg had a lower iPTHP=0.007and a higher serum Ca/Mg ratioP<0.001than the other CKD patients. The lower serum Mg subgroup showed a higher incidence of osteoporosis than the moderate and higher serum Mg subgroups did (66.7%, 39.4%, and 29.4%, resp.). In conclusion, low serum Mg may impact iPTH and exacerbates osteoporosis in CKD patients, particularly with diabetes.

scholarly journals Rhubarb Enema Decreases Circulating Trimethylamine N-Oxide Level and Improves Renal Fibrosis Accompanied With Gut Microbiota Change in Chronic Kidney Disease Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunlan Ji ◽  
Yin Li ◽  
Yenan Mo ◽  
Zhaoyu Lu ◽  
Fuhua Lu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intestinal Microbiota ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Underlying Mechanism ◽  
Uremic Toxins ◽  
16S Rrna Sequence ◽  
Tubular Atrophy ◽  
The Impact

Objectives: Trimethylamine N-oxide (TMAO), a metabolic product of gut flora, is increased in chronic kidney disease (CKD) subjects and is recognized as one type of uremic toxins which is associated with poor cardiovascular outcomes and kidney function loss. Previous studies have suggested that rhubarb enema could reduce circulating uremic toxins such as urea, creatinine, and indoxyl sulfate and also regulate the intestinal microbiota. However, whether rhubarb enema retards kidney dysfunction by reducing circulating TMAO and its underlying mechanism, are still unclear. The present study aims to investigate the impact of rhubarb enema on TMAO and its precursors, as well as on the intestinal microbiota in 5/6 nephrectomized (5/6Nx) CKD rats.Design: Rats in the treatment groups were given rhubarb enema after modeling. At the end of the study, blood, feces, and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses.Results: Rhubarb enema reduced serum TMAO and trimethylamine (TMA) levels, inhibited the expression of inflammatory markers (interleukin-6, tumor necrosis factor α and Interferon-γ) and alleviated tubular atrophy, monocyte infiltration and interstitial fibrosis in 5/6Nx CKD rats. Moreover, rhubarb enema significantly increased the abundance of some symbiotic bacteria and probiotics, while reduced the abundance of some potential pathogens at the genus level. In addition, Spearman’s correlation analysis revealed that lachnospiraceae and romboutsia were positively correlated with TMAO.Conclusion: Rhubarb enema decreases circulating TMAO level and improves renal fibrosis in 5/6Nx CKD rats, which may be related to the regulation of intestinal microbial community.

scholarly journals Ketoacid Analogues Supplementation in Chronic Kidney Disease and Future Perspectives

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2071 ◽  
Author(s):  
Laetitia Koppe ◽  
Mariana Cassani de Oliveira ◽  
Denis Fouque
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Uremic Toxins ◽  
Protein Diet ◽  
Current Evidence ◽  
Low Protein ◽  
The Impact

Diet is a key component of care during chronic kidney disease (CKD). Nutritional interventions, and, specifically, a restricted protein diet has been under debate for decades. In order to reduce the risk of nutritional disorders in very-low protein diets (VLDP), supplementation by nitrogen-free ketoacid analogues (KAs) have been proposed. The aim of this review is to summarize the potential effects of this dietary therapy on renal function, uremic toxins levels, and nutritional and metabolic parameters and propose future directions. The purpose of this paper is also to select all experimental and randomized clinical studies (RCTs) that have compared VLDP + KA to normal diet or/and low protein diet (LPD). We reviewed the SCOPUS, WEB of SCIENCES, CENTRAL, and PUBMED databases from their inception to 1 January, 2019. Following duplicate removal and application of exclusion criteria, 23 RCTs and 12 experimental studies were included. LPD/VLPD + KAs appear nutritionally safe even if how muscle protein metabolism adapts to an LPD/VLPD + KAs is still largely unknown. VLPD + KAs seem to reduce uremic toxins production but the impact on intestinal microbiota remains unexplored. All studies observed a reduction of acidosis, phosphorus, and possibly sodium intake, while still providing adequate calcium intake. The impact of this diet on carbohydrate and bone parameters are only preliminary and need to be confirmed with RCTs. The Modification of Diet in Renal Disease study, the largest RCTs, failed to demonstrate a benefit in the primary outcome of the decline rate for the glomerular filtration rate. However, the design of this study was challenged and data were subsequently reanalyzed. However, when adherent patients were selected, with a rapid rate of progression and a long-term follow up, more recent meta-analysis and RCTs suggest that these diets can reduce the loss of the glomerular filtration rate in addition to the beneficial effects of renin-angiotensin-aldosterone system (RAAS) inhibitors. The current evidence suggests that KAs supplemented LPD diets should be included as part of the clinical recommendations for both the nutritional prevention and metabolic management of CKD. More research is needed to examine the effectiveness of KAs especially on uremic toxins. A reflection about the dose and composition of the KAs supplement, the cost-effective features, and their indication to reduce the frequency of dialysis needs to be completed.

scholarly journals The Impact of CKD on Uremic Toxins and Gut Microbiota

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 252
Author(s):  
Jacek Rysz ◽  
Beata Franczyk ◽  
Janusz Ławiński ◽  
Robert Olszewski ◽  
Aleksanda Ciałkowska-Rysz ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Microbial Community ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Adverse Outcomes ◽  
Uremic Toxins ◽  
Dietary Interventions ◽  
Stress Injury ◽  
The Impact

Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an “imbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota”. The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD.

scholarly journals Uremic Toxins, Oxidative Stress, Atherosclerosis in Chronic Kidney Disease, and Kidney Transplantation

2021 ◽  
Vol 2021 ◽  
pp. 1-15 ◽  
Author(s):  
Ewa Wojtaszek ◽  
Urszula Oldakowska-Jedynak ◽  
Marlena Kwiatkowska ◽  
Tomasz Glogowski ◽  
Jolanta Malyszko
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Uremic Toxins ◽  
Transplant Recipients ◽  
Risk Of Death ◽  
The Impact

Patients with chronic kidney disease (CKD) are at a high risk for cardiovascular disease (CVD), and approximately half of all deaths among patients with CKD are a direct result of CVD. The premature cardiovascular disease extends from mild to moderate CKD stages, and the severity of CVD and the risk of death increase with a decline in kidney function. Successful kidney transplantation significantly decreases the risk of death relative to long-term dialysis treatment; nevertheless, the prevalence of CVD remains high and is responsible for approximately 20-35% of mortality in renal transplant recipients. The prevalence of traditional and nontraditional risk factors for CVD is higher in patients with CKD and transplant recipients compared with the general population; however, it can only partly explain the highly increased cardiovascular burden in CKD patients. Nontraditional risk factors, unique to CKD patients, include proteinuria, disturbed calcium, and phosphate metabolism, anemia, fluid overload, and accumulation of uremic toxins. This accumulation of uremic toxins is associated with systemic alterations including inflammation and oxidative stress which are considered crucial in CKD progression and CKD-related CVD. Kidney transplantation can mitigate the impact of some of these nontraditional factors, but they typically persist to some degree following transplantation. Taking into consideration the scarcity of data on uremic waste products, oxidative stress, and their relation to atherosclerosis in renal transplantation, in the review, we discussed the impact of uremic toxins on vascular dysfunction in CKD patients and kidney transplant recipients. Special attention was paid to the role of native and transplanted kidney function.

MO550INDOXYL SULFATE AFFECTS ERYTHROPOIESIS DURING THE COURSE OF CHRONIC KIDNEY DISEASE: A MOLECULAR STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Eya Hamza ◽  
Hakim Ouled-Haddou ◽  
Nicolas Jankovsky ◽  
Yohann Demont ◽  
Benjamin Brigant ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cell Line ◽  
Uremic Toxins ◽  
Erythroid Cell ◽  
Uremic Toxin ◽  
Cd34 Cells ◽  
Phase Cycle ◽  
The Impact

Abstract Background and Aims Chronic kidney disease (CKD) is a global health condition characterized by a progressive deterioration of renal function due to high serum levels of uremic toxins. Anemia is a major trouble in CKD patients that contributes to a faster deterioration of renal failure, leading to cardiovascular disease and increasing morbimortality. Erythropoietin (EPO) is known to contribute to CKD-associated anemia. Thus, accumulation of uremic toxins in blood impairs EPO synthesis, leading to a subsequent impairment of erythropoiesis in the bone marrow. Very few molecular clues explain why erythropoiesis is affected in CKD or explain why erythropoiesis-stimulating agents (ESA) are not efficient in some patients with CKD. The current study aims to characterize the impact of one of the most representative uremic toxins, Indoxyl Sulfate (IS), in CKD-related anemia. IS is a protein-bound uremic toxin derived from the tryptophan dietary metabolism which is difficult to remove by dialysis. Our study demonstrates the molecular effects of IS on the growth and the differentiation of red blood cells in an erythroid cell line and in primary cell cultures CD34+. Method Firstly, we examined in vitro the time-courses of IS under clinically relevant concentrations of IS (250 µM -1 mM) in a human leukemic cell line in which proliferation is induced by EPO, the UT7/EPO cell line. Cell apoptosis, proliferation, differentiation and cell cycle analysis were assessed by the MACSQuant flow cytometry. Erythroid gene expression analysis was assessed by RT-qPCR (Quantstudio 7 flex). The ratio A260/280 assessed the quality of nucleic acids. Western blotting experiments were performed to study protein expression. Human primary CD34+ cells were obtained from mobilized peripheral blood mononuclear cells (MNC) of healthy subjects and were isolated by magnetic microbeads separation on MACS columns. Results IS at 250 µM and 1 mM increased apoptosis of UT7/EPO cell line at 48h compared to control condition. On the other hand, we found no significant effect of IS on the phenotype of UT7/EPO, when using CD235a (Glycophorin A), as a marker for the detection of the erythroid cell lineage. Ki67 cellular levels, a cell proliferation marker, was not altered between control and IS experiments. This indicated that IS did not affect proliferation in UT7/EPO. At 48h, at the clinically relevant concentration of IS (250 µM), we observed an increase of the cell phase cycle Sub-G1. The analysis of erythropoiesis related genes shows that HIF2α was deregulated with IS (250 µM). Finally, in the Epo-EpoR signalling pathway, we studied the activation of the Jak2/Stat5 proteins. Results in human primary CD34+ cells confirmed the apoptotic effect of IS observed in UT7/EPO. Conclusion Our findings suggest that IS, a representative protein-bound uremic toxin, could affect cell viability, apoptosis and the cell cycle. This study suggests clues to develop new therapies for CKD-associated anemia.

3285Impact of intravascular ultrasound-guided percutaneous coronary intervention in patients with diabetes mellitus and chronic kidney disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Sato ◽  
K Sakamoto ◽  
T Yamashita ◽  
S Nagamatsu ◽  
K Motozato ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Risk Group ◽  
Coronary Intervention ◽  
Cardiovascular Death ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Stent Diameter ◽  
The Impact

Abstract Background Several studies have shown favorable results using IVUS-guided PCI. Nevertheless, patient background in which use of IVUS is effective is not well elucidated. Patients with diabetes mellitus (DM) or chronic kidney disease (CKD) tend to have complex coronary artery lesions. We sought to assess the impact of IVUS guidance on clinical outcomes in these patients. Methods Kumamoto Intervention Conference Study is a multicenter registry which has enrolled consecutive patients who underwent PCI in 16 centers in Japan. Between August 2008 and March 2014, 11,195 consecutive patients were enrolled in this registry. To elucidate the efficacy of IVUS usage in DM and CKD patients, 10,822 consecutive subjects with 1-year follow-up data were analyzed. In this patient population, 69.2% (n=7,493) of patients were treated with IVUS-guided PCI. Patients were divided into 4 groups: the No Risk Group, the DM only Group, the CKD only Group, and the DM+CKD Group. Results Maximum stent diameter, post dilatation rate, usage of distal protection device, and rotational atherectomy rate were significantly higher in the IVUS-guided PCI patients in all 4 groups. 1-year MACE (cardiovascular death, non-fatal myocardial infarction, and MI with stent thrombosis) was significantly lower in the IVUS-guided PCI patients than angiography-guided PCI patients in each subset, except for the No Risk Group. In contrast to angiography-guided PCI patients, there were no significant differences among the 4 groups as regards 1-year MACE in the IVUS-guided PCI patients except for the DM+CKD Group. In multiple regression analysis, IVUS usage was an independent negative predictor for 1-year MACE in the DM only Group (HR=0.374, 95% CI 0.194–0.719, p=0.003) and in the CKD only Group (HR=0.604, 95% CI 0.379–0.962, p=0.010). When the No Risk Group was used as a reference, the HR has increased according to increased risk factors in the angiography-guided PCI patients, but such tendency was not necessarily observed in the IVUS-guided PCI patients (Table). Risk Stratification of DM and CKD Variable IVUS-Guided PCI Angiography-Guided PCI HR 95% CI P HR 95% CI P The No Risk Group Reference – – Reference – –   vs. the DM only Group 0.627 0.321–1.227 0.173 2.036 1.090–3.804 0.026   vs. the CKD only Group 1.334 0.795–2.237 0.275 2.730 1.541–4.836 0.001   vs. the DM+CKD Group 2.114 1.287–3.474 0.014 2.225 1.160–4.266 0.016 Conclusion The efficacy of IVUS usage as regards 1-year MACE was confirmed in DM and CKD patients, but not observed in patients without them or in the combination of DM and CKD patients. Acknowledgement/Funding None

scholarly journals The Impact of Uremia and Intestinal Dysbiosis on Hepatic Drug Metabolism in a Rat Model of Progressive Chronic Kidney Disease

2019 ◽  
Author(s):  
Emily D Hartjes ◽  
Yong Jin Lim ◽  
Thomas J Velenosi ◽  
Kait F Al ◽  
Jean M Macklaim ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Drug Metabolism ◽  
Gut Microbiota ◽  
Uremic Toxins ◽  
Uremic Toxin ◽  
Bacterial Microbiota ◽  
Intestinal Dysbiosis ◽  
Metabolite Profiles ◽  
The Impact

AbstractNonrenal clearance pathways such as drug metabolism are decreased in chronic kidney disease (CKD). Although the mechanism remains elusive, uremic toxin retention and an altered gut microbiota are suspected to influence cytochrome P450s (CYPs) contributing to the unpredictable pharmacokinetics in patients with CKD. We characterized dysbiosis and uremia in CKD to elucidate associations between CYP expression and CKD progression. Rats fed control or CKD-inducing adenine diet were subsequently studied at five time points over 42 days. CYP expression and activity were compared to alterations in the 1) plasma and liver metabolome and 2) gut bacterial microbiota. CYP3A2 and CYP2C11 were downregulated in CKD by ≥76% (p<0.001) concurrently with or slightly prior to CKD onset as defined by serum creatinine. Metabolite profiles were altered prior to changes in the gut microbiota, and gut-derived uremic toxins including indoxyl sulfate, phenyl sulfate and 4-ethylphenyl sulfate correlated with CYP3A2 or CYP2C11 expression. Bacterial genera Turicibacter and Parabacteroides were identified as being characteristic of CKD. In conclusion, CYP3A2 and CYP2C11 are downregulated before dysbiosis and correlate with select uremic toxins.

scholarly journals Risk for recurrent cardiovascular disease events among patients with diabetes and chronic kidney disease

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Demetria Hubbard ◽  
Lisandro D. Colantonio ◽  
Robert S. Rosenson ◽  
Todd M. Brown ◽  
Elizabeth A. Jackson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Health Insurance ◽  
High Risk ◽  
Kidney Disease ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Very High

Abstract Background Adults who have experienced multiple cardiovascular disease (CVD) events have a very high risk for additional events. Diabetes and chronic kidney disease (CKD) are each associated with an increased risk for recurrent CVD events following a myocardial infarction (MI). Methods We compared the risk for recurrent CVD events among US adults with health insurance who were hospitalized for an MI between 2014 and 2017 and had (1) CVD prior to their MI but were free from diabetes or CKD (prior CVD), and those without CVD prior to their MI who had (2) diabetes only, (3) CKD only and (4) both diabetes and CKD. We followed patients from hospital discharge through December 31, 2018 for recurrent CVD events including coronary, stroke, and peripheral artery events. Results Among 162,730 patients, 55.2% had prior CVD, and 28.3%, 8.3%, and 8.2% had diabetes only, CKD only, and both diabetes and CKD, respectively. The rate for recurrent CVD events per 1000 person-years was 135 among patients with prior CVD and 110, 124 and 171 among those with diabetes only, CKD only and both diabetes and CKD, respectively. Compared to patients with prior CVD, the multivariable-adjusted hazard ratio for recurrent CVD events was 0.92 (95%CI 0.90–0.95), 0.89 (95%CI: 0.85–0.93), and 1.18 (95%CI: 1.14–1.22) among those with diabetes only, CKD only, and both diabetes and CKD, respectively. Conclusion Following MI, adults with both diabetes and CKD had a higher risk for recurrent CVD events compared to those with prior CVD without diabetes or CKD.

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