Bone and vascular effects of magnesium supplements in CKD patients (the MagicalBone Pilot Study).

Background And Objective: The progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3-4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC).

Uremic Toxins Induce THP-1 Monocyte Endothelial Adhesion and Migration through Specific miRNA Expression.

Atherosclerosis is initiated by the activation of endothelial cells that allows monocyte adhesion and transmigration through the vascular wall. The accumulation of uremic toxins such as indoxyl sulphate (IS) and p-cresol (PC) has been associated with atherosclerosis. Currently, miRNAs play a crucial role in the regulation of monocyte activation, adhesion, and trans-endothelial migration.

The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function.

Background: In chronic kidney disease (CKD) patients, increased levels of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality. The relationship between FGF23 and heart hypertrophy has been documented, however, it is not known whether FGF23 has an effect on vasculature. Vascular smooth muscle cells VSMCs may exhibit different phenotypes; our hypothesis is that FGF23 favours a switch from a contractile to synthetic phenotype that may cause vascular dysfunction.

Passage Number-Induced Replicative Senescence Modulates the Endothelial Cell Response to Protein-Bound Uremic Toxins.

Endothelial aging may be induced early in pathological situations. The uremic toxins indoxyl sulfate (IS) and p-cresol (PC) accumulate in the plasma of chronic kidney disease (CKD) patients, causing accelerated endothelial aging, increased cardiovascular events and mortality. However, the mechanisms by which uremic toxins exert their deleterious effects on endothelial aging are not yet fully known.

Predicting mortality in hemodialysis patients using machine learning analysis.

Background: Besides the classic logistic regression analysis, non-parametric methods based on machine learning techniques such as random forest are presently used to generate predictive models. The aim of this study was to evaluate random forest mortality prediction models in haemodialysis patients.

Methods: Data were acquired from incident haemodialysis patients between 1995 and 2015.

Assessment of Inorganic Phosphate Intake by the Measurement of the Phosphate/Urea Nitrogen Ratio in Urine.

In chronic kidney disease (CKD) patients, it would be desirable to reduce the intake of inorganic phosphate (P) rather than limit the intake of P contained in proteins. Urinary excretion of P should reflect intestinal absorption of P(inorganic plus protein-derived). The aim of the present study is to determine whether the ratio of urinary P to urinary urea nitrogen (P/UUN ratio) helps identify patients with a high intake of inorganic P.

Inflammation, Senescence and MicroRNAs in Chronic Kidney Disease.

Background: Patients with chronic kidney disease (CKD) show a chronic microinflammatory state that promotes premature aging of the vascular system. Currently, there is a growth interest in the search of novel biomarkers related to vascular aging to identify CKD patients at risk to develop cardiovascular complications.

Methods: Forty-five CKD patients were divided into three groups according to CKD-stages [predialysis (CKD4-5), hemodialysis (HD) and kidney transplantation (KT)].

Role of endothelial microvesicles released by p-cresol on endothelial dysfunction.

Protein bound uremic toxins, such as p-cresol, cannot be effectively removed by conventional dialysis techniques and are accumulated in plasma, thus contributing to progression of both chronic kidney disease (CKD) and cardiovascular disease (CVD). Pathological effects of uremic toxins include activation of inflammatory response, endothelial dysfunction and release of endothelial microvesicles. To date, the role of p-cresol in endothelial microvesicles formation has not been analyzed.

Hemodiafiltration with ultrafiltrate regeneration reduces free light chains without albumin loss in multiple myeloma patients.

Background: Acute kidney injury (AKI) occurs in 12-20% of multiple myeloma (MM) patients. Several studies have shown a reduction of free light chains (FLC) using hemodialysis with High-Cut-Off membranes. However, this technique entails albumin loss.

Phosphate control in reducing FGF23 levels in hemodialysis patients.

Background: In hemodialysis patients, high levels of Fibroblast Growth Factor 23 (FGF23) predict mortality. Our study was designed to test whether the control of serum phosphate is associated with a reduction in serum FGF23 levels. Additionally other variables with a potential effect on FGF23 levels were evaluated.

Hemodiafiltration With Endogenous Reinfusion Improved Microinflammation and Endothelial Damage Compared With Online-Hemodiafiltration: A Hypothesis Generating Study.

Hemodiafiltration with endogenous reinfusion (HFR) after ultrafiltrate passage through a resin cartridge combines adsorption, convection, and diffusion. Our prospective single-center crossover study compared HFR and online-hemodiafiltration (OLHDF) effects on two uremic toxins and 13 inflammatory, endothelial status, or oxidative stress markers. After an 8-week run-in period of high-flux hemodialysis, 17 eligible stable dialysis patients (median age 65 years, 10 male) without overt clinical inflammation were scheduled for four 8-week periods in the sequence: HFR/OLHDF/HFR/OLHDF.

Efficiency of Original versus Generic Intravenous Iron Formulations in Patients on Haemodialysis.

Aims: The appropriate use of intravenous (i.v.) iron is essential to minimise the requirements for erythropoiesis-stimulating agents (ESAs).

Endothelial damage and vascular calcification in patients with chronic kidney disease.

Vascular calcification (VC) is a frequent complication of chronic kidney disease (CKD) and is a predictor of cardiovascular morbidity and mortality. In the present study, we investigated the potential involvement of endothelial microparticles (MPs) and endothelial progenitor cells (EPCs) in the generation of VC in CKD patients. The number of circulating EMPs is greater in patients with VC than without VC (307 ± 167 vs.

Klotho Prevents NFκB Translocation and Protects Endothelial Cell From Senescence Induced by Uremia.

In patients with renal disease, uremia raises oxidative stress and senescence in endothelial cells, which can lead to endothelial dysfunction and cardiovascular disease. Klotho protein is a β-glucuronidase capable of hydrolyzing steroid β-glucuronides. This protein is recognized as an antiaging gene, that modulate both stress-induced senescence and functional response.

Cellular senescence determines endothelial cell damage induced by uremia.

Renal dysfunction is closely associated with endothelial damage leading to cardiovascular disease. However, the extent to which endothelial damage induced by uremia is modulated by aging is poorly known. Aging can render endothelial cells more susceptible to apoptosis through an oxidative stress-dependent pathway.

The effect of phosphate binders, calcium and lanthanum carbonate on FGF23 levels in chronic kidney disease patients.

Background: Recent publications show that elevation of FGF23 is independently associated with progression or renal disease, left ventricular hypertrophy and cardiovascular mortality. Dietary restriction of phosphate and phosphate binders are used for control phosphate balance and elevation of serum FGF23 levels. The aim of this study is to compare the effectiveness of calcium carbonate vs.

Effects of intravenous iron on mononuclear cells during the haemodialysis session.

Background: This study analysed, in vivo and in vitro, the effects of four different intravenous iron preparations (iron gluconate, iron sucrose, iron dextran and ferric carboxymaltose) on activation and damage of mononuclear cells.

Methods: A randomized prospective study was conducted in 10 haemodialysis (HD) patients. Blood samples were collected at baseline (T0); 1 h after starting HD, just before the iron or saline administration (T1); 30 min after the iron or saline infusion (T2) and at the end of HD (T3).

Tandem plasmapheresis and hemodialysis: efficacy and safety.

Background: Hemodialysis (HD) and plasmapheresis (PE) are usually performed independently on patients who require renal replacement therapy. We analyzed our experience using a technique that performs both modalities simultaneously.

Methods: Thirty-six patients who were treated with 287 tandem PE and HD (TPH) sessions (mean 7.

CD14+CD16+ monocytes from chronic kidney disease patients exhibit increased adhesion ability to endothelial cells.

Chronic kidney disease (CKD) patients present an inflammatory process that induces endothelial damage and therefore plays a role in the high rates of cardiovascular morbidity and mortality reported in these patients. Although new therapies have reduced the elevated serum levels of inflammatory mediators such as cytokines and CRP in CKD patients, the rise in the level of activated immunocompetent cells is maintained in peripheral blood, which appears to play a prominent role in the endothelial damage suffered by these patients. CD14+CD16+ monocytes are a subset of activated monocytes that are found in greater numbers in the peripheral blood of CKD patients.

Carbamylated low-density lipoprotein induces oxidative stress and accelerated senescence in human endothelial progenitor cells.

Carbamylated low-density lipoprotein (cLDL) plays a role in atherosclerosis. In this study we evaluate the effect of uremia on LDL carbamylation and the effect of cLDL and oxidized LDL (oxLDL; 200 μg/ml) on number, function, and genomic stability of endothelial progenitor cells (EPCs) obtained from healthy volunteers. cLDL was generated after incubation of native LDL (nLDL) with uremic serum from patients with chronic kidney disease (CKD) stages 2-4.

Replicative senescence in patients with chronic kidney failure.

Background: Chronic activation of immunocompetent cells may lead to stress-induced premature senescence (SIPS); these senescent cells are characterized by a decrease in telomere length. The present study evaluates SIPS in circulating immunocompetent cells from predialysis patients, patients on hemodialysis, and in renal transplant patients with normal renal function.

Methods: Determination of telomere length by flow-fluorescence in situ hybridization (FISH), expression of surface molecules, and evaluation of apoptosis was performed by flow cytometry.

Monocytes from dialysis patients exhibit characteristics of senescent cells: does it really mean inflammation?

Hemodialysis treatment induces mononuclear cell activation particularly if cellulosic hemodialysis membrane is used. In normal cells, repeated activation induce a process of accelerate cellular senescence. The aim of the present study was to evaluate whether the mononuclear cell activation associated to hemodialysis with cellulosic membranes favors a process of accelerate senescence in mononuclear cells.