scholarly journals High cut-off dialysis mitigates pro-calcific effects of plasma on vascular progenitor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Theres Schaub ◽  
Daniel Janke ◽  
Daniel Zickler ◽  
Claudia Lange ◽  
Matthias Girndt ◽  
...  
Keyword(s):  
Osteoblastic Differentiation ◽  
Cardiovascular Toxicity ◽  
Vascular Regeneration ◽  
Screening Experiments ◽  
Vascular Progenitor Cells ◽  
Stage Renal Disease ◽  
End Stage ◽  
Physiologic Role ◽  
Direct Toxicity ◽  
Pro Inflammatory Cytokines

AbstractMortality of patients with end-stage renal disease tremendously exceeds that of the general population due to excess cardiovascular morbidity. Large middle-sized molecules (LMM) including pro-inflammatory cytokines are major drivers of uremic cardiovascular toxicity and cannot be removed sufficiently by conventional high-flux (HFL) hemodialysis. We tested the ability of plasma from 19 hemodialysis patients participating in a trial comparing HFL with high cut-off (HCO) membranes facilitating removal of LMM to induce calcification in mesenchymal stromal cells (MSC) functioning as vascular progenitors. HCO dialysis favorably changed plasma composition resulting in reduced pro-calcific activity. LMM were removed more effectively by HCO dialysis including FGF23, a typical LMM we found to promote osteoblastic differentiation of MSC. Protein-bound uremic retention solutes with known cardiovascular toxicity but not LMM inhibited proliferation of MSC without direct toxicity in screening experiments. We could not attribute the effect of HCO dialysis on MSC calcification to distinct mediators. However, we found evidence of sustained reduced inflammation that might parallel other anti-calcifying mechanisms such as altered generation of extracellular vesicles. Our findings imply protection of MSC from dysfunctional differentiation by novel dialysis techniques targeted at removal of LMM. HCO dialysis might preserve their physiologic role in vascular regeneration and improve outcomes in dialysis patients.

scholarly journals A Novel Formulation of Glucose-Sparing Peritoneal Dialysis Solutions with l-Carnitine Improves Biocompatibility on Human Mesothelial Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 123
Author(s):  
Francesca Piccapane ◽  
Mario Bonomini ◽  
Giuseppe Castellano ◽  
Andrea Gerbino ◽  
Monica Carmosino ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Mesothelial Cells ◽  
Apical Side ◽  
New Formulation ◽  
Stage Renal Disease ◽  
End Stage ◽  
Dialysis Solutions ◽  
Pro Inflammatory Cytokines

The main reason why peritoneal dialysis (PD) still has limited use in the management of patients with end-stage renal disease (ESRD) lies in the fact that the currently used glucose-based PD solutions are not completely biocompatible and determine, over time, the degeneration of the peritoneal membrane (PM) and consequent loss of ultrafiltration (UF). Here we evaluated the biocompatibility of a novel formulation of dialytic solutions, in which a substantial amount of glucose is replaced by two osmometabolic agents, xylitol and l-carnitine. The effect of this novel formulation on cell viability, the integrity of the mesothelial barrier and secretion of pro-inflammatory cytokines was evaluated on human mesothelial cells grown on cell culture inserts and exposed to the PD solution only at the apical side, mimicking the condition of a PD dwell. The results were compared to those obtained after exposure to a panel of dialytic solutions commonly used in clinical practice. We report here compelling evidence that this novel formulation shows better performance in terms of higher cell viability, better preservation of the integrity of the mesothelial layer and reduced release of pro-inflammatory cytokines. This new formulation could represent a step forward towards obtaining PD solutions with high biocompatibility.

scholarly journals Serum exosomes from diabetic kidney disease patients promote pyroptosis and oxidative stress through the miR-4449/HIC1 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chan Gao ◽  
Benyong Wang ◽  
Qi Chen ◽  
Ming Wang ◽  
Xiao Fei ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Protein Levels ◽  
Qrt Pcr ◽  
Stage Renal Disease ◽  
End Stage ◽  
Serum Exosomes ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Abstract Background Diabetic kidney disease (DKD) is a major contributor to end-stage renal disease. Several microRNAs (miRNAs) have been found to be enriched in exosomes of DKD patients, but it remains unclear if any of these miRNAs play an important role in the pathogenesis of DKD. Methods Exosomes from diabetic kidney disease (DKD) patients were isolated, and the expression of miR-4449 was measured by qRT-PCR. Reactive oxygen species (ROS) was determined by DCDFA assay kit, and pyroptosis was measured by quantifying the level of activated caspase 1. mRNA and protein levels were quantified by qRT-PCR and WB. Results In this study, we demonstrated that miR-4449 is enriched in the serum exosomes of DKD patients, and these exosomes regulate the expression of pro-inflammatory cytokines, ROS levels, and pyroptosis through miR-4449. Conclusions Our study uncovered a novel mechanism for the progression of DKD that is mediated through miR-4449 in serum exosomes, which highlights an important role for exosomes in the pathogenesis of DKD.

scholarly journals New Insights on End-Stage Renal Disease and Healthy Individual Gut Bacterial Translocation: Different Carbon Composition of Lipopolysaccharides and Different Impact on Monocyte Inflammatory Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Hanane Adda-Rezig ◽  
Clémence Carron ◽  
Jean-Paul Pais de Barros ◽  
Hélène Choubley ◽  
Émilie Charron ◽  
...  
Keyword(s):  
Renal Disease ◽  
Bacterial Translocation ◽  
End Stage Renal Disease ◽  
Lipid A ◽  
Carbon Chain ◽  
Carbon Chain Length ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients ◽  
Pro Inflammatory Cytokines

Chronic kidney disease induces disruption of the intestinal epithelial barrier, leading to gut bacterial translocation. Here, we appreciated bacterial translocation by analyzing circulating lipopolysaccharides (LPS) using two methods, one measuring only active free LPS, and the other quantifying total LPS as well as LPS lipid A carbon chain length. This was done in end-stage renal disease (ESRD) patients and healthy volunteers (HV). We observed both higher LPS concentration in healthy volunteers and significant differences in composition of translocated LPS based on lipid A carbon chain length. Lower LPS activity to mass ratio and higher concentration of high-density lipoproteins were found in HV, suggesting a better plasma capacity to neutralize LPS activity. Higher serum concentrations of soluble CD14 and pro-inflammatory cytokines in ESRD patients confirmed this hypothesis. To further explore whether chronic inflammation in ESRD patients could be more related to LPS composition rather than its quantity, we tested the effect of HV and patient sera on cytokine secretion in monocyte cultures. Sera with predominance of 14-carbon chain lipid A-LPS induced higher secretion of pro-inflammatory cytokines than those with predominance of 18-carbon chain lipid A-LPS. TLR4 or LPS antagonists decreased LPS-induced cytokine production by monocytes, demonstrating an LPS-specific effect. Thereby, septic inflammation observed in ESRD patients may be not related to higher bacterial translocation, but to reduced LPS neutralization capacity and differences in translocated LPS subtypes.

Serum Thiamine Values in End-Stage Renal Disease Patients under Maintenance Hemodialysis

2015 ◽  
Vol 85 (5-6) ◽  
pp. 348-355 ◽  
Author(s):  
Masamitsu Ubukata ◽  
Nobuyuki Amemiya ◽  
Kosaku Nitta ◽  
Takashi Takei
Keyword(s):  
Thiamine Deficiency ◽  
Risk Index ◽  
Nutritional Risk ◽  
Maintenance Hemodialysis ◽  
Dialysis Patients ◽  
Significant Difference ◽  
Nutritional Risk Index ◽  
Serum Aspartate Aminotransferase ◽  
Stage Renal Disease ◽  
End Stage

Abstract. Objective: Hemodialysis patients are prone to malnutrition because of diet or many uremic complications. The objective of this study is to determine whether thiamine deficiency is associated with regular dialysis patients. Methods: To determine whether thiamine deficiency is associated with regular dialysis patients, we measured thiamine in 100 patients undergoing consecutive dialysis. Results: Average thiamine levels were not low in both pre-hemodialysis (50.1 ± 75.9 ng/mL; normal range 24 - 66 ng/mL) and post-hemodialysis (56.4 ± 61.7 ng/mL). In 18 patients, post-hemodialysis levels of thiamine were lower than pre-hemodialysis levels. We divided the patients into two groups, the decrease (Δthiamine/pre thiamine < 0; - 0.13 ± 0.11) group (n = 18) and the increase (Δthiamine/pre thiamine> 0; 0.32 ± 0.21)) group (n = 82). However, there was no significance between the two groups in Kt/V or type of dialyzer. Patients were dichotomized according to median serum thiamine level in pre-hemodialysis into a high-thiamine group (≥ 35.5 ng/mL) and a low-thiamine group (< 35.4 ng/mL), and clinical characteristics were compared between the two groups. The low-thiamine value group (< 35.4 ng/ml; 26.8 ± 5.3 ng/ml) exhibited lower levels of serum aspartate aminotransferase and alanine aminotransferase than the high-thiamine value group (≥ 35.4 ng/ml; 73.5 ± 102.5 ng/ml) although there was no significance in nutritional marker, Alb, geriatric nutritional risk index , protein catabolic rate and creatinine generation rate. Conclusion: In our regular dialysis patients, excluding a few patients, we did not recognize thiamine deficiency and no significant difference in thiamine value between pre and post hemodialysis.

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