scholarly journals Platelets of patients with chronic kidney disease demonstrate deficient platelet reactivity in vitro

2012 ◽  
Vol 13 (1) ◽  
Author(s):  
Esther R van Bladel ◽  
Rosa L de Jager ◽  
Daisy Walter ◽  
Loes Cornelissen ◽  
Carlo A Gaillard ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Platelet Reactivity

scholarly journals Soluble Fas affects erythropoiesis in vitro and acts as a potential predictor of erythropoiesis-stimulating agent therapy in patients with chronic kidney disease

2020 ◽  
Vol 318 (4) ◽  
pp. F861-F869
Author(s):  
Daniela Mendes Chiloff ◽  
Danilo Candido de Almeida ◽  
Maria A. Dalboni ◽  
Maria Eugênia Canziani ◽  
Sunil K. George ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Dependent Manner ◽  
Potential Predictor ◽  
Soluble Fas ◽  
Esa Therapy

Serum soluble Fas (sFas) levels are associated with erythropoietin (Epo) hyporesponsiveness in patients with chronic kidney disease (CKD). Whether sFas could predict the need for erythropoiesis-stimulating agent (ESA) usage and its influence in erythropoiesis remain unclear. We evaluated the relation between sFas and ESA therapy in patients with CKD with anemia and its effect on erythropoiesis in vitro. First, we performed a retrospective cohort study with 77 anemic patients with nondialysis CKD. We performed in vitro experiments to investigate whether sFas could interfere with the behavior of hematopoietic stem cells (HSCs). HSCs were isolated from umbilical cord blood and incubated with recombinant sFas protein in a dose-dependent manner. Serum sFas positively correlated with Epo levels ( r = 0.30, P = 0.001) but negatively with hemoglobin ( r = −0.55, P < 0.001) and glomerular filtration rate ( r = −0.58, P < 0.001) in patients with CKD at baseline. Elevated sFas serum levels (4,316 ± 897 vs. 2,776 ± 749, P < 0.001) with lower estimated glomerular filtration rate (26.2 ± 10.1 vs. 33.5 ± 14.3, P = 0.01) and reduced hemoglobin concentration (11.1 ± 0.9 vs. 12.5 ± 1.2, P < 0.001) were identified in patients who required ESA therapy compared with patients with non-ESA. Afterward, we detected that the sFas level was slight correlated with a necessity of ESA therapy in patients with nondialysis CKD and anemia. In vitro assays demonstrated that the erythroid progenitor cell frequency negatively correlated with sFas concentration ( r = −0.72, P < 0.001). There was decreased erythroid colony formation in vitro when CD34+ HSCs were incubated with a higher concentration of sFas protein (1.56 ± 0.29, 4.33 ± 0.53, P < 0.001). Our findings suggest that sFas is a potential predictor for ESA therapy in patients with nondialysis CKD and that elevated sFas could affect erythropoiesis in vitro.

Nutritional compounds influence tissue factor expression and inflammation of chronic kidney disease patients in vitro

Nutrition ◽  
2011 ◽  
Vol 27 (9) ◽  
pp. 967-972 ◽  
Author(s):  
Cecilia M. Shing ◽  
Murray J. Adams ◽  
Robert G. Fassett ◽  
Jeff S. Coombes
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tissue Factor ◽  
Tissue Factor Expression ◽  
Factor Expression ◽  
Nutritional Compounds

scholarly journals Paracrine Proangiogenic Function of Human Bone Marrow-Derived Mesenchymal Stem Cells Is Not Affected by Chronic Kidney Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Femke C. C. van Rhijn-Brouwer ◽  
Bas W. M. van Balkom ◽  
Diana A. Papazova ◽  
Diënty H. M. Hazenbrink ◽  
Anke J. Meijer ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Bone Marrow ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Galactosidase Activity ◽  
Kidney Transplant Recipients ◽  
Paracrine Factors ◽  
Differentiation Capacity ◽  
Scratch Wound

Background. Cell-based therapies are being developed to meet the need for curative therapy in chronic kidney disease (CKD). Bone marrow- (BM-) derived mesenchymal stromal cells (MSCs) enhance tissue repair and induce neoangiogenesis through paracrine action of secreted proteins and extracellular vesicles (EVs). Administration of allogeneic BM MSCs is less desirable in a patient population likely to require a kidney transplant, but potency of autologous MSCs should be confirmed, given previous indications that CKD-induced dysfunction is present. While the immunomodulatory capacity of CKD BM MSCs has been established, it is unknown whether CKD affects wound healing and angiogenic potential of MSC-derived CM and EVs. Methods. MSCs were cultured from BM obtained from kidney transplant recipients (N=15) or kidney donors (N=17). Passage 3 BM MSCs and BM MSC-conditioned medium (CM) were used for experiments. EVs were isolated from CM by differential ultracentrifugation. BM MSC differentiation capacity, proliferation, and senescence-associated β-galactosidase activity was assessed. In vitro promigratory and proangiogenic capacity of BM MSC-derived CM and EVs was assessed using an in vitro scratch wound assay and Matrigel angiogenesis assay. Results. Healthy and CKD BM MSCs exhibited similar differentiation capacity, proliferation, and senescence-associated β-galactosidase activity. Scratch wound migration was not significantly different between healthy and CKD MSCs (P=0.18). Healthy and CKD BM MSC-derived CM induced similar tubule formation (P=0.21). There was also no difference in paracrine regenerative function of EVs (scratch wound: P=0.6; tubulogenesis: P=0.46). Conclusions. Our results indicate that MSCs have an intrinsic capacity to produce proangiogenic paracrine factors, including EVs, which is not affected by donor health status regarding CKD. This suggests that autologous MSC-based therapy is a viable option in CKD.

scholarly journals Relation of Functional Activity of Platelets to Prognosis of Unfavorable Cardiovascular Events in Patients with Acute Coronary Syndrome. Results of a Registry Study

Kardiologiia ◽  
2019 ◽  
Vol 59 (10) ◽  
pp. 5-13
Author(s):  
N. V. Lomakin ◽  
L. I. Buryachkovskaya ◽  
A. B. Sumarokov ◽  
Z. A. Gabbasov ◽  
A. N. Gerasimov
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Coronary Syndrome ◽  
Platelet Aggregation ◽  
Kidney Disease ◽  
Functional Activity ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Coronary Syndrome ◽  
C Statistic

Aim: to assess relation ofhigh functional activity ofplatelets to prognosis ofunfavorable cardiovascular events in patients with Acute Coronary Syndrome (ACS).Materials. The study was based on the data of a single center ACS registry conducted in the Central Clinical Hospital of the Presidential Affairs Department of Russian Federation. Of 529 included patients in 425 without contraindications to double antiplatelet therapy we carried out analysis of dependence of 30 days level of unfavorable events on parameters of functional activity of platelets.Results. High on-treatment platelet reactivity (HTPR) was found to be associated with 3.5 increase of mortality in the group of patients with high cardiovascular risk. Logistic model of prognosis of unfavorable events based on multifactorial analysis of data from patients with measured platelet aggregation included chronic kidney disease, type of myocardial infarction, and degree ofplatelet aggregation >45%. C -statistic was equal to 0.77. We also present in this paper discussion of problems related to studying approaches to individualization of anti-aggregation therapy in real clinical practice and problems of organization ofsimilar studies.Conclusion. The study showed that patients with ACS increased platelet aggregation, as well as chronic kidney disease and type 2 MI are associated with a 30 day prognosis of adverse events.

Receptor for advanced glycation end products: a key molecule in the genesis of chronic kidney disease vascular calcification and a potential modulator of sodium phosphate co-transporter PIT-1 expression

2019 ◽  
Vol 34 (12) ◽  
pp. 2018-2030 ◽  
Author(s):  
Karim Belmokhtar ◽  
Jeremy Ortillon ◽  
Stéphane Jaisson ◽  
Ziad A Massy ◽  
Camille Boulagnon Rombi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Advanced Glycation End Products ◽  
Mrna Levels ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
High Phosphate

Abstract Background Chronic kidney disease (CKD) is associated with increased cardiovascular mortality, frequent vascular calcification (VC) and accumulation of uraemic toxins. Advanced glycation end products and S100 proteins interact with the receptor for advanced glycation end products (RAGE). In the present work, we aimed to investigate the role(s) of RAGE in the CKD–VC process. Methods Apoe−/− or Apoe−/−Ager (RAGE)−/− male mice were assigned to CKD or sham-operated groups. A high-phosphate diet was given to a subgroup of Apoe−/−and Apoe−/−Ager−/− CKD mice. Primary cultures of Ager+/+ and Ager−/− vascular smooth muscle cells (VSMCs) were established and stimulated with either vehicle, inorganic phosphate (Pi) or RAGE ligands (S100A12; 20 µM). Results After 12 weeks of CKD we observed a significant increase in RAGE ligand (AGE and S100 proteins) concentrations in the serum of CKD Apoe−/− mice. Ager messenger RNA (mRNA) levels were 4-fold higher in CKD vessels of Apoe−/− mice. CKD Apoe−/− but not CKD Apoe−/− or Ager−/− mice displayed a marked increase in the VC surface area. Similar trends were found in the high-phosphate diet condition. mRNA levels of Runx2 significantly increased in the Apoe−/− CKD group. In vitro, stimulation of Ager+/+VSMCs with Pi or S100A12 induced mineralization and osteoblast transformation, and this was inhibited by phosphonoformic acid (Pi co-transporters inhibitor) and Ager deletion. In vivo and in vitro RAGE was necessary for regulation of the expression of Pit-1, at least in part through production of reactive oxygen species. Conclusion RAGE, through the modulation of Pit-1 expression, is a key molecule in the genesis of VC.

scholarly journals Calciprotein particle inhibition explains magnesium-mediated protection against vascular calcification

2019 ◽  
Vol 35 (5) ◽  
pp. 765-773 ◽  
Author(s):  
Anique D ter Braake ◽  
Coby Eelderink ◽  
Lara W Zeper ◽  
Andreas Pasch ◽  
Stephan J L Bakker ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Healthy Controls ◽  
Gene And Protein Expression ◽  
Calciprotein Particles

Abstract Background Phosphate (Pi) toxicity is a strong determinant of vascular calcification development in chronic kidney disease (CKD). Magnesium (Mg2+) may improve cardiovascular risk via vascular calcification. The mechanism by which Mg2+ counteracts vascular calcification remains incompletely described. Here we investigated the effects of Mg2+ on Pi and secondary crystalline calciprotein particles (CPP2)-induced calcification and crystal maturation. Methods Vascular smooth muscle cells (VSMCs) were treated with high Pi or CPP2 and supplemented with Mg2+ to study cellular calcification. The effect of Mg2+ on CPP maturation, morphology and composition was studied by medium absorbance, electron microscopy and energy dispersive spectroscopy. To translate our findings to CKD patients, the effects of Mg2+ on calcification propensity (T50) were measured in sera from CKD patients and healthy controls. Results Mg2+ supplementation prevented Pi-induced calcification in VSMCs. Mg2+ dose-dependently delayed the maturation of primary CPP1 to CPP2 in vitro. Mg2+ did not prevent calcification and associated gene and protein expression when added to already formed CPP2. Confirmatory experiments in human serum demonstrated that the addition of 0.2 mmol/L Mg2+ increased T50 from healthy controls by 51 ± 15 min (P &lt; 0.05) and CKD patients by 44 ± 13 min (P &lt; 0.05). Each further 0.2 mmol/L addition of Mg2+ led to further increases in both groups. Conclusions Our results demonstrate that crystalline CPP2 mediates Pi-induced calcification in VSMCs. In vitro, Mg2+ delays crystalline CPP2 formation and thereby prevents Pi-induced calcification.

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