Differences in association between hypoalbuminaemia and mortality among younger versus older patients on haemodialysis.

Background: Ageing often affects biomarker production. Yet, clinical/optimal thresholds to guide clinical decisions do not consider this. Serum albumin decreases with age, but hypoalbuminaemia is defined as serum albumin <4.

RANKL, but Not R-Spondins, Is Involved in Vascular Smooth Muscle Cell Calcification through LGR4 Interaction.

Vascular calcification has a global health impact that is closely linked to bone loss. The Receptor Activator of Nuclear Factor Kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, fundamental for bone metabolism, also plays an important role in vascular calcification. The Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), a novel receptor for RANKL, regulates bone remodeling, and it appears to be involved in vascular calcification.

Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care.

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD ("Chronic Kidney Disease-Mineral and Bone Disorders") complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain.

Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease-Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows.

Shortly after the discovery of Klotho, interest grew in its potential role in chronic kidney disease (CKD). There are three isoforms of the Klotho protein: αKlotho, βKlotho and γKlotho. This review will focus on αKlotho due to its relevance as a biomarker in CKD.

Serum phosphate is associated with increased risk of bone fragility fractures in haemodialysis patients.

Background: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of chronic kidney disease-mineral and bone disorders (CKD-MBD) and bone fragility fractures in the COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) project.

Methods: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 haemodialysis patients (227 centres from 20 European countries).

Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis.

Chronic kidney disease (CKD) is a highly prevalent disease that has become a public health problem. Progression of CKD is associated with serious complications, including the CKD-mineral and bone disorder (CKD-MBD). Laboratory, bone and vascular abnormalities define this condition, and all have been independently related to cardiovascular disease and high mortality rates.

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.

Novel Immune Cell Subsets Exhibit Different Associations With Vascular Outcomes in Chronic Kidney Disease Patients-Identifying Potential Biomarkers.

Alterations in novel immune cell subsets, such as angiogenic T cells (Tang), senescent T cells (CD4CD28), and monocyte subsets are associated with impaired vascular homeostasis in several inflammatory conditions. However, mediators underlying vascular deterioration in chronic kidney disease (CKD) are poorly characterized. This study assessed their role in the vascular deterioration of CKD using a broad spectrum of surrogate markers ranging from altered functionality to overt calcification.

The Non-invasive Diagnosis of Bone Disorders in CKD.

Abnormal bone metabolism is an integral part of the chronic kidney disease-mineral bone disorder (CKD-MBD). For several reasons, the difficult bone compartment was neglected for some time, but there has been renewed interest as a result of the conception of bone as a new endocrine organ, the increasing recognition of the cross-talk between bone and vessels, and, especially, the very high risk of osteoporotic fractures (and associated mortality) demonstrated in patients with CKD. Therefore, it has been acknowledged in different guidelines that action is needed in respect of fracture risk assessment and the diagnosis and treatment of osteoporosis in the context of CKD and CKD-MBD, even beyond renal osteodystrophy.

The receptor activator of nuclear factor κΒ ligand receptor leucine-rich repeat-containing G-protein-coupled receptor 4 contributes to parathyroid hormone-induced vascular calcification.

Background: In chronic kidney disease, serum phosphorus (P) elevations stimulate parathyroid hormone (PTH) production, causing severe alterations in the bone-vasculature axis. PTH is the main regulator of the receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, which is essential for bone maintenance and also plays an important role in vascular smooth muscle cell (VSMC) calcification. The discovery of a new RANKL receptor, leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), which is important for osteoblast differentiation but with an unknown role in vascular calcification (VC), led us to examine the contribution of LGR4 in high P/high PTH-driven VC.

A subset of low density granulocytes is associated with vascular calcification in chronic kidney disease patients.

Inflammation is central to chronic kidney disease (CKD) pathogenesis and vascular outcomes, but the exact players remain unidentified. Since low density granulocytes (LDGs) are emerging mediators in inflammatory conditions, we aimed to evaluate whether LDGs may be altered in CKD and related to clinical outcomes as biomarkers. To his end, LDGs subsets were measured in peripheral blood by flow cytometry and confocal microscopy in 33 CKD patients undergoing peritoneal dialysis and 15 healthy controls (HC).

Osteoporosis, bone mineral density and CKD-MBD (II): Therapeutic implications.

Osteoporosis (OP) and chronic kidney disease (CKD) both independently affect bone health. A significant number of patients with CKD have decreased bone mineral density (BMD), are at high risk of fragility fractures and have an increased morbidity and mortality risk. With an ageing population, these observations are not only dependent on "renal osteodystrophy" but also on the associated OP.

Osteoporosis, bone mineral density and CKD-MBD complex (I): Diagnostic considerations.

Osteoporosis (OP) and chronic kidney disease (CKD) independently influence bone and cardiovascular health. A considerable number of patients with CKD, especially those with stages 3a to 5D, have a significantly reduced bone mineral density leading to a high risk of fracture and a significant increase in associated morbidity and mortality. Independently of classic OP related to age and/or gender, the mechanical properties of bone are also affected by inherent risk factors for CKD ("uraemic OP").

Improvement of mineral and bone metabolism markers is associated with better survival in haemodialysis patients: the COSMOS study.

Background: Abnormalities in serum phosphorus, calcium and parathyroid hormone (PTH) have been associated with poor survival in haemodialysis patients. This COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) analysis assesses the association of high and low serum phosphorus, calcium and PTH with a relative risk of mortality. Furthermore, the impact of changes in these parameters on the relative risk of mortality throughout the 3-year follow-up has been investigated.

[Cinacalcet in the management of normocalcaemic secondary hyperparathyroidism after kidney transplantation: one-year follow-up multicentre study].

Background: The effect of cinacalcet in patients with persistent secondary hyperparathyroidism (SHPT) after kidney transplantation (RT) has mainly been reported in patients with secondary hypercalcaemia.

Objectives: Our objective was to assess the long-term effect of cinacalcet on patients with a RT and normocalcaemic SHPT.

Methods: A one-year multicentre, observational, retrospective study that included kidney recipients with SHPT (intact parathyroid hormone [iPTH] >120 pg/ml) and calcium levels within the normal range (8.

Cinacalcet for hypercalcaemic secondary hyperparathyroidism after renal transplantation: a multicentre, retrospective, 3-year study.

Aims: Our aim was to evaluate the long-term effect of cinacalcet in patients with hypercalcaemic secondary hyperparathyroidism (SHPT) after renal transplantation (RT) in order to expand real-world data in this population.

Methods: We performed a multicentre, observational, retrospective study in 17 renal transplant units from Spain. We collected data from renal recipients with hypercalcaemic (calcium >10.

COSMOS: the dialysis scenario of CKD-MBD in Europe.

Background: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are important complications of CKD5D patients that are associated with mortality.

Methods: COSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005-07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions.

Osteoporosis and adynamic bone in chronic kidney disease.

Among the chronic kidney disease-mineral bone disease (CKD-MBD) disorders, osteoporosis and adynamic bone are highly prevalent, and they have been consistently associated with low bone mass, bone fractures, vascular calcifications and greater mortality in general and CKD populations. Despite the fact that osteoporosis and adynamic bone have similar clinical outcomes, they have different pathogeneses and clinical management. In osteoporosis, there is a lack of balance between bone formation and bone resorption, and less new bone is formed to replace bone losses.

Vascular calcification in patients with chronic kidney disease: types, clinical impact and pathogenesis.

Vascular calcification plays a major role in cardiovascular disease, which is one of the main causes of mortality in chronic kidney disease patients. Vascular calcification is determined by prevalent traditional and uraemia-related (non-traditional) risk factors. It occurs mainly in the arteries, which are classified into three types according to their size and structural characteristics.

New therapies: calcimimetics, phosphate binders and vitamin D receptor activators.

At present, new compounds are available to treat secondary hyperparathyroidism, namely calcimimetics, novel phosphorus binders and also novel vitamin D receptor activators. Calcimimetics increase the sensitivity of the parathyroid gland to calcium through spatial configurational changes of the calcium-sensing receptor. In addition, experimental studies have demonstrated that calcimimetics also upregulate both the calcium-sensing receptor and the vitamin D receptor.

Vascular calcifications, vertebral fractures and mortality in haemodialysis patients.

Background: Vascular calcifications and the bone fractures caused by abnormal bone fragility, also called osteoporotic fractures, are frequent complications associated with chronic kidney diseases (CKD). The aim of this study was to investigate the association between vascular calcifications, osteoporotic bone fractures and survival in haemodialysis (HD) patients.

Methods: A total of 193 HD patients were followed up to 2 years.

Vascular calcifications: pathogenesis, management, and impact on clinical outcomes.

The predisposition to vascular calcifications in patients with chronic kidney disease (CKD) has gained great interest in recent years as many studies have described its likely impact on morbidity and mortality. The mechanism by which the process of vascular calcification is produced is complex, and it does not consist in a simple precipitation of calcium and phosphate but is instead an active and modifiable process. Several "modifiable and nonmodifiable" factors that are able to promote vascular calcification are extremely frequent in patients with CKD.

Advantages of adjusting the initial dose of intravenous calcitriol according to PTH levels.

Background: To assess the usefulness of starting calcitriol therapy with a dose proportional to the degree of hyperparathyroidism, 141 patients from 28 centers were treated with intravenous calcitriol for 6 months. The aim was to achieve a final PTH between 125 and 250 pg/mL. Patients with serum PTH>250 pg/mL were included in the study and divided into 4 groups according to baseline PTH levels.

Hyperphosphataemia as a cardiovascular risk factor -- how to manage the problem.

Hyperphosphataemia is a frequent and important cardiovascular risk factor in patients with chronic kidney disease (CKD). High phosphate levels may influence vascular calcifications by two separate mechanisms: by worsening secondary hyperparathyroidism, which in turn facilitates calcification, and by promoting calcium phosphate deposition in pre-formed endothelial plaques and in the arterial wall. Recent studies have shown that hyperphosphataemia induces the proliferation and differentiation of endothelial vascular cells into osteoblast-like cells, promoting vascular calcification.