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).

Hemodiafiltration with endogenous reinfusion of the regenerated ultrafiltrate (HFR): towards a convective, diffusive, and adsorptive dialysis.

Hemodiafiltration with endogenous reinfusion of the ultrafiltrate (HFR) is a dialysis technique characterized by a resin cartridge with adsorptive properties that combines the mechanisms of diffusion, convection, and adsorption in a single therapeutic regimen. After nearly 20 years of clinical experience with HFR, this article reviews the accumulated evidence with this technique, considering whether adsorption reduction, as a third purification mechanism, should be the next step in the treatment of hemodialysis patients. HFR, beyond producing an extensive removal of uremic toxins, has demonstrated to reduce the loss of nutrients and other physiological components during the dialysis session as compared to online hemodiafiltration, ameliorating the inflammatory state and oxidative stress in this population.

Unresolved aspects in the management of renal anemia, a Delphi consensus of the Anemia Group of the S.E.N.

Anemia is a common complication of chronic kidney disease (CKD) and is associated with a decrease in quality of life and an increased risk of transfusions, morbidity and mortality, and progression of CKD. The Anemia Working Group of the Sociedad Española de Nefrología conducted a Delphi study among experts in anemia in CKD to agree on relevant unanswered questions by existing evidence. The RAND/UCLA consensus methodology was used.

A selenoureido-iminoglycolipid transported by zeolitic-imidazolate framework nanoparticles: a novel antioxidant therapeutic approach.

A selenium-containing metal-organic framework with remarkable antioxidant capacity and ROS-scavenging activity was constructed by a controlled encapsulation approach of a glycoconjugate mimetic, specifically a sp-iminoglycolipid bearing a selenoureido fragment (DSeU), within a zeolitic-imidazolate framework exoskeleton. Biocompatible and homogeneous nanosized particles of ∼70 nm (DSeU@ZIF8) were obtained, which could be efficiently internalized in cells, overcoming the poor solubility in biological media and limited bioavailability of glycolipids. The ZIF-particle served as nanocarrier for the intracellular delivery of the selenocompound to cells, promoted by the acidic pH inside endosomes/lysosomes.

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.

Silver jubilee: 25 years of the first demonstration of the direct effect of phosphate on the parathyroid cell.

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism (SHPT) in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr.

Safety and effectiveness of sucroferric oxyhydroxide in Spanish patients on dialysis: sub-analysis of the VERIFIE study.

Background And Aims: In this study, we show the results of the subset of Spanish patients of the VERIFIE study, the first post-marketing study assessing the long-term safety and effectiveness of sucroferric oxyhydroxide (SFOH) in patients with hyperphosphatemia undergoing dialysis during clinical practice.

Patients And Methods: Patients undergoing hemodialysis and peritoneal dialysis with indication of SFOH treatment were included. Follow-up duration was 12-36 months after SFOH initiation.

Incorporating zeolitic-imidazolate framework-8 nanoparticles into kidney scaffolds: a first step towards innovative renal therapies.

We demonstrate for the first time the potential of zeolitic-imidazolate framework-8 nanoparticles to be incorporated within a renal scaffold while retaining their ability to remove uremic toxins (mainly hydrophobic toxins like -cresol) under flow conditions. This work may pave the way for the future development of novel adsorbents for dialysis and/or artificial kidneys.

Hyporesponsiveness or resistance to the action of parathyroid hormone in chronic kidney disease.

Secondary hyperparathyroidism (SHPT) is an integral component of the chronic kidney disease-mineral and bone disorder (CKD-MBD). Many factors have been associated with the development and progression of SHPT but the presence of skeletal or calcemic resistance to the action of PTH in CKD has often gone unnoticed. The term hyporesponsiveness to PTH is currently preferred and, in this chapter, we will not only review the scientific timeline but also some of the molecular mechanisms behind.

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.

Survival with low- and high-flux dialysis.

Background: Besides advances in haemodialysis (HD), mortality rates are still high. The effect of the different types of HD membranes on survival is still a controversial issue. The aim of this COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) analysis was to survey, in HD patients, the relationship between the use of conventional low- or high-flux membranes and all-cause and cardiovascular mortality.

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.

Control of phosphorus and prevention of fractures in the kidney patient.

Patients with chronic kidney disease have a higher risk of fractures than the general population due to the added factor of uraemia. Although the mechanisms behind uraemia-associated fractures are not fully understood, it is widely accepted that the decrease in bone mineral content and alteration in bone architecture both increase bone fragility. As chronic kidney disease progresses, the risk of fracture increases, especially once the patient requires dialysis.

The Role of Disturbed Mg Homeostasis in Chronic Kidney Disease Comorbidities.

Some of the critical mechanisms that mediate chronic kidney disease (CKD) progression are associated with vascular calcifications, disbalance of mineral metabolism, increased oxidative and metabolic stress, inflammation, coagulation abnormalities, endothelial dysfunction, or accumulation of uremic toxins. Also, it is widely accepted that pathologies with a strong influence in CKD progression are diabetes, hypertension, and cardiovascular disease (CVD). A disbalance in magnesium (Mg) homeostasis, more specifically hypomagnesemia, is associated with the development and progression of the comorbidities mentioned above, and some mechanisms might explain why low serum Mg is associated with negative clinical outcomes such as major adverse cardiovascular and renal events.

Control of phosphorus and prevention of fractures in the kidney patient.

Patients with chronic kidney disease have a higher risk of fractures than the general population due to the added factor of uraemia. Although the mechanisms behind uraemia-associated fractures are not fully understood, it is widely accepted that the decrease in bone mineral content and alteration in bone architecture both increase bone fragility. As chronic kidney disease progresses, the risk of fracture increases, especially once the patient requires dialysis.

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.

Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease.

Fibroblast Growth Factor 23 (FGF23) and Klotho play an essential role in the regulation of mineral metabolism, and both are altered as a consequence of renal failure. FGF23 increases to augment phosphaturia, which prevents phosphate accumulation at the early stages of chronic kidney disease (CKD). This effect of FGF23 requires the presence of Klotho in the renal tubules.