Special Issue "The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD)"

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Uremic Toxins".

Deadline for manuscript submissions: closed (30 June 2019).

Special Issue Editors

Prof. Dr. Marc G. Vervloet
E-Mail Website
Guest Editor
Department of Nephrology and Institute of Cardiovascular Research, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
Prof. Dr. Mario Cozzolino
E-Mail Website
Guest Editor
Department of Health Sciences, Renal Division, San Paolo Hospital, University of Milan, Milan, Italy

Special Issue Information

Dear Colleagues,

For long times the field of CKD-MBD has been dominated by abnormalities in the concentrations of PTH, vitamin D, phosphate, FGF23 and calcium. Direct associations between these factors in isolation have been described, usually pointing to u-shaped associations with clinical endpoints. These observational data form base of current treatment guidelines.

Recently, rapidly expanding insights are changing the landscape of CKD-MBD. Novel insights point to more complex pathological mechanisms that connect classical biomarkers, in particular PTH and phosphate to clinical disease. Phosphate emerges as an integral component of a specific uremic milieu that drives vascular disease, suggesting that targeting phosphate toxicity is more than targeting hyperphosphatemia. In addition, the perspective on both PTH and bone is shifting from isolated factors to complex regulatory systems, which may culminate in different treatment paradigms for the future. In addition to changing views on classical biomarkers, more components appear to contribute to the syndrome of CKD-MBD. Among those are disturbed homeostasis of Magnesium, the role of macrophages in uremia-associated vascular disease, and recently discovered humoral systems like activin-activation in CKD

These exciting new aspects are all covered in this Special Issue of Toxins, entirely dedicated to the moving field of CKD-MBD. This issue is created in close collaboration with the ERA-EDTA working group on CKD-MBD and is Guest-Edited by Professors Mario Cozzolino and Professor Marc Vervloet.

Prof. Dr. Marc G. Vervloet
Prof. Dr. Mario Cozzolino
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CKD-MBD
  • Phosphate
  • PTH
  • Cardiovascular disease
  • Macrophages
  • Bone disease
  • Senescence

Published Papers (5 papers)

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Research

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Article
Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis
Toxins 2019, 11(7), 428; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11070428 - 21 Jul 2019
Cited by 21 | Viewed by 2114
Abstract
Sclerostin is a well-known inhibitor of bone formation that acts on Wnt/β-catenin signaling. This manuscript considers the possible role of sclerostin in vascular calcification, a process that shares many similarities with physiological bone formation. Rats were exposed to a warfarin-containing diet to induce [...] Read more.
Sclerostin is a well-known inhibitor of bone formation that acts on Wnt/β-catenin signaling. This manuscript considers the possible role of sclerostin in vascular calcification, a process that shares many similarities with physiological bone formation. Rats were exposed to a warfarin-containing diet to induce vascular calcification. Vascular smooth muscle cell transdifferentiation, vascular calcification grade, and bone histomorphometry were examined. The presence and/or production of sclerostin was investigated in serum, aorta, and bone. Calcified human aortas were investigated to substantiate clinical relevance. Warfarin-exposed rats developed vascular calcifications in a time-dependent manner which went along with a progressive increase in serum sclerostin levels. Both osteogenic and adipogenic pathways were upregulated in calcifying vascular smooth muscle cells, as well as sclerostin mRNA and protein levels. Evidence for the local vascular action of sclerostin was found both in human and rat calcified aortas. Warfarin exposure led to a mildly decreased bone and mineralized areas. Osseous sclerostin production and bone turnover did not change significantly. This study showed local production of sclerostin in calcified vessels, which may indicate a negative feedback mechanism to prevent further calcification. Furthermore, increased levels of serum sclerostin, probably originating from excessive local production in calcified vessels, may contribute to the linkage between vascular pathology and impaired bone mineralization. Full article
(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))
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Review

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Review
New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease
Toxins 2019, 11(9), 529; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11090529 - 12 Sep 2019
Cited by 9 | Viewed by 1963
Abstract
Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney disease (CKD), and cardiovascular calcification (CVC) is one of the strongest predictors of CVD in this population. Cardiovascular calcification results from complex cellular interactions involving the endothelium, vascular/valvular cells [...] Read more.
Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney disease (CKD), and cardiovascular calcification (CVC) is one of the strongest predictors of CVD in this population. Cardiovascular calcification results from complex cellular interactions involving the endothelium, vascular/valvular cells (i.e., vascular smooth muscle cells, valvular interstitial cells and resident fibroblasts), and monocyte-derived macrophages. Indeed, the production of pro-inflammatory cytokines and oxidative stress by monocyte-derived macrophages is responsible for the osteogenic transformation and mineralization of vascular/valvular cells. However, monocytes/macrophages show the ability to modify their phenotype, and consequently their functions, when facing environmental modifications. This plasticity complicates efforts to understand the pathogenesis of CVC—particularly in a CKD setting, where both uraemic toxins and CKD treatment may affect monocyte/macrophage functions and thereby influence CVC. Here, we review (i) the mechanisms by which each monocyte/macrophage subset either promotes or prevents CVC, and (ii) how both uraemic toxins and CKD therapies might affect these monocyte/macrophage functions. Full article
(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))
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Review
Modifying Phosphate Toxicity in Chronic Kidney Disease
Toxins 2019, 11(9), 522; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11090522 - 09 Sep 2019
Cited by 8 | Viewed by 1963
Abstract
Phosphate toxicity is a well-established phenomenon, especially in chronic kidney disease (CKD), where hyperphosphatemia is a frequent occurrence when CKD is advanced. Many therapeutic efforts are targeted at phosphate, and comprise dietary intervention, modifying dialysis schemes, treating uncontrolled hyperparathyroidism and importantly, phosphate binder [...] Read more.
Phosphate toxicity is a well-established phenomenon, especially in chronic kidney disease (CKD), where hyperphosphatemia is a frequent occurrence when CKD is advanced. Many therapeutic efforts are targeted at phosphate, and comprise dietary intervention, modifying dialysis schemes, treating uncontrolled hyperparathyroidism and importantly, phosphate binder therapy. Despite all these interventions, hyperphosphatemia persists in many, and its pathological influence is ongoing. In nephrological care, a somewhat neglected aspect of treatment—when attempts fail to lower exposure to a toxin like phosphate—is to explore the possibility of “anti-dotes”. Indeed, quite a long list of factors modify, or are mediators of phosphate toxicity. Addressing these, especially when phosphate itself cannot be sufficiently controlled, may provide additional protection. In this narrative overview, several factors are discussed that may qualify as either such a modifier or mediator, that can be influenced by other means than simply lowering phosphate exposure. A wider scope when targeting phosphate-induced comorbidity in CKD, in particular cardiovascular disease, may alleviate the burden of disease that is the consequence of this potentially toxic mineral in CKD. Full article
(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))
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Review
The Key Role of Phosphate on Vascular Calcification
Toxins 2019, 11(4), 213; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11040213 - 09 Apr 2019
Cited by 37 | Viewed by 2922
Abstract
Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD [...] Read more.
Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD patients, although it has not been proven. There are more than one type of VC and every form represents a marker of systemic vascular disease and is associated with a higher prevalence of CVD in CKD patients, as shown by several clinical studies. Major risk factors for VC in CKD include: Increasing age, dialysis vintage, hyperphosphatemia (particularly in the setting of intermittent or persistent hypercalcemia), and a positive net calcium and phosphate balance. Excessive oral calcium intake, including calcium-containing phosphate binders, increases the risk for VC. Moreover, it has been demonstrated that there is less VC progression with non-calcium-containing phosphate binders. Unfortunately, until now, a specific therapy to prevent progression or to facilitate regression of VC has been found, beyond careful attention to calcium and phosphate balance. Full article
(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))
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Review
Senescent Cells in Early Vascular Ageing and Bone Disease of Chronic Kidney Disease—A Novel Target for Treatment
Toxins 2019, 11(2), 82; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11020082 - 01 Feb 2019
Cited by 12 | Viewed by 2348
Abstract
Together with bone-mineral disorders, premature vascular ageing is a common feature of the uremic phenotype. A detailed understanding of mechanisms involved remains unclear and warrants further research. Available treatment options for end stage renal disease are principally dialysis and organ transplantation, as other [...] Read more.
Together with bone-mineral disorders, premature vascular ageing is a common feature of the uremic phenotype. A detailed understanding of mechanisms involved remains unclear and warrants further research. Available treatment options for end stage renal disease are principally dialysis and organ transplantation, as other treatment alternatives have proven insufficient. Chronic kidney disease (CKD) has been proposed as a model of early vascular and bone ageing, with accumulating evidence supporting the contribution of cellular senescence and the senescence-associated secretory phenotype (SASP) to cardiovascular pathology in CKD. Correspondingly, novel therapies based around the use of senolytic compounds and nuclear factor-erythroid-2-related factor 2 (Nrf2) agonists, have been suggested as attractive novel treatment options. In this review, we detail the contribution of the uremic environment to these processes underpinning ageing and how these relate to vascular health. Full article
(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))
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