News on Biomarkers in CKD‐MBD

Mazzaferro, Sandro; Tartaglione, Lida; Rotondi, Silverio; Bover, Jordi; Goldsmith, David; Pasquali, Marzia

doi:10.1016/j.semnephrol.2014.09.006

Cited by 43 publications

(36 citation statements)

References 135 publications

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“…In haemodialysis patients the imbalance of osteoprotegerin (OPG)-RANKL system, whatever the cause may be, are involved in HSC egress from the bone marrow [8, 27]. …”

Section: Discussionmentioning

confidence: 99%

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Is chronic kidney disease-mineral and bone disorder associated with the presence of endothelial progenitor cells with a calcifying phenotype?

Cianciolo

Capelli

Cappuccilli

et al. 2017

Clinical Kidney Journal

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Background: Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been implicated in vascular calcification pathogenesis. CKD-MBD results in alterations in the number and function of circulating endothelial progenitor cells (EPCs), physiological regulators of angiogenesis and vessel repair, commonly defined as proangiogenic progenitor cells (PACs) by the antigen pattern CD34+CD133+KDR+CD45– and putative EPCs by the pattern CD34+CD133−KDR+CD45–. These cells might acquire a calcifying phenotype in CKD-MBD, expressing mineralization biomarkers. We investigated the expression of vitamin D receptor (VDR) and osteocalcin (OC) on EPCs of healthy individuals and haemodialysis patients, and their possible associations with circulating biomarkers of inflammation and vascular calcification. Methods: We compared EPC counts, expressing VDR or OC, in 23 healthy subjects versus 53 haemodialysis patients, 17 of them without vitamin D receptor agonist (VDRA) therapy and 35 treated with calcitriol (n = 17) or paricalcitol (n = 18). The correlations with serum levels of inflammatory and calcification indexes were also analysed. Results: All subsets expressing VDR or OC were significantly higher in haemodialysis patients compared with healthy controls, but PACs were increased only in VDRA treatment subgroup, while putative EPCs showed a similar rise also in untreated patients. In VDRA-untreated patients, OC+ PACs correlated positively with calcium levels, while in VDRA-treated patients, VDR+ PACs correlated positively with interleukin 6 levels, and OC+ PACs correlated positively 25-hydroxyvitamin D levels. Conclusions: Our data suggest that in CKD-MBD, EPCs undergo an endothelial-to-procalcific shift, representing a risk factor for vascular calcification. A link between mineral disorders and vitamin D replacement therapy emerged, with potential adverse effects for CKD patients.

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“…In haemodialysis patients the imbalance of osteoprotegerin (OPG)-RANKL system, whatever the cause may be, are involved in HSC egress from the bone marrow [8, 27]. …”

Section: Discussionmentioning

confidence: 99%

“…OC is a noncollagenous bone protein implicated in bone mineralization and calcium homeostasis, while BAP is a glycoprotein found on osteoblast surface, essential for mineralization process [8]. …”

Section: Introductionmentioning

confidence: 99%

Is chronic kidney disease-mineral and bone disorder associated with the presence of endothelial progenitor cells with a calcifying phenotype?

Cianciolo

Capelli

Cappuccilli

et al. 2017

Clinical Kidney Journal

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“…Therefore, the clinical use of PTH (PTH monitoring and goals) is controversial (86,87). Nevertheless, because maintenance of appropriate PTH levels remains one of the main goals in contemporary nephrology practice, it probably should be monitored not only on a regular basis but also more frequently, at least until more specific new biomarkers and/or drugs with different targets demonstrate clinical superiority over current standard nephrology protocols (4,30).…”

Section: Pth Oversuppressionmentioning

confidence: 99%

“…Multiple CKD-related derangements may account for the extremely high mortality observed in these patients (1) and, among these disturbances, CKD-related mineral and bone disorders (CKD-MBDs) seem to play an important role (1)(2)(3). Classic biochemical alterations of calcium (Ca), phosphate (P), Ca 3 P product, parathyroid hormone (PTH), and other bone-related biomarkers have been increasingly associated, although not uniformly, with prediction of bone disease and also with CV events and survival (2)(3)(4)(5). On the other hand, it has been suggested that patients with CKD stages 3-5D, with known vascular or valvular calcifications, should be considered at the highest CV risk; therefore, it seems reasonable to use this information to guide the management of CKD-MBD (3,(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism

Bover

Ureña

Ruiz-García

et al. 2016

Clinical Journal of the American Society of Nephrology

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CKD and CKD-related mineral and bone disorders (CKD-MBDs) are associated with high cardiovascular and mortality risks. In randomized clinical trials (RCTs), no single drug intervention has been shown to reduce the high mortality risk in dialysis patients, but several robust secondary analyses point toward important potential beneficial effects of controlling CKD-MBD-related factors and secondary hyperparathyroidism. The advent of cinacalcet, which has a unique mode of action at the calcium-sensing receptor, represented an important step forward in controlling CKD-MBD. In addition, new RCTs have conclusively shown that cinacalcet improves achievement of target levels for all of the metabolic abnormalities associated with CKD-MBD and may also attenuate the progression of vascular and valvular calcifications in dialysis patients. However, a final conclusion on the effect of cinacalcet on hard outcomes remains elusive. Tolerance of cinacalcet is limited by frequent secondary side effects such as nausea, vomiting, hypocalcemia and oversuppression of parathyroid hormone, which may cause some management difficulties, especially for those lacking experience with the drug. Against this background, this review aims to summarize the results of studies on cinacalcet, up to and including the publication of the recent ADVANCE and EVOLVE RCTs, as well as recent post hoc analyses, and to offer practical guidance on how to improve the clinical management of the most frequent adverse events associated with cinacalcet, based on both currently available information and personal experience. In addition, attention is drawn to less common secondary effects of cinacalcet treatment and advisable precautions.

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“…A great number of other classic markers of bone metabolism like parathyroid hormone (PTH), OC and also vitamin K, MGP and many other noncollagenous bone proteins take a significant part in the process of calcification [43]. However, their diagnostic role and potential implications in clinical practice need further assessments.…”

Section: Role Of Bone Biologymentioning

confidence: 99%

Osteoporosis and cardiovascular disease: an update

Lello

Capozzi

Scambia

2015

Gynecological Endocrinology

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Osteoporosis (OP) and cardiovascular diseases (CVD) are the most important causes of mortality and morbility in the elderly. Lots of studies showed a correlation between bone loss and cardiovascular risk mediated by the vascular calcification. The relationship between OP and CVD could be firstly explained by their common risk factors such as age, smoking, alcohol consumption, physical activity and menopause. However, other different hypotheses were proposed to clarify this link. Multiple factors, for example bone morphogenetic proteins, osteoprotegerin, receptor activator of nuclear factor κB ligand, parathyroid hormone, phosphate, oxidized lipids and vitamins D and K seemed to be involved in both conditions, indicating a possible common pathophysiologic mechanism. We review and discuss the available data describing this association. Further studies are necessary to better investigate similarities between OP and CVD.

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News on Biomarkers in CKD‐MBD

Cited by 43 publications

References 135 publications

Is chronic kidney disease-mineral and bone disorder associated with the presence of endothelial progenitor cells with a calcifying phenotype?

Is chronic kidney disease-mineral and bone disorder associated with the presence of endothelial progenitor cells with a calcifying phenotype?

Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism

Osteoporosis and cardiovascular disease: an update

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