Phosphorylated fetuin-A-containing calciprotein particles are associated with aortic stiffness and a procalcific milieu in patients with pre-dialysis CKD

Smith, Edwin R.; Ford, Martin; Tomlinson, Laurie; Rajkumar, Chakravarthi; McMahon, Lawrence P.; Holt, Stephen G

doi:10.1093/ndt/gfr609

Cited by 159 publications

(190 citation statements)

References 66 publications

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“…18 CPPs occur in vivo in pathologic situations like CKD, which are characterized by concentration changes of proteinaceous or mineral calcification inhibitors or promotors. [19][20][21] In analogy, fetuin-mineral complexes were found in bisphosphonate-treated hypercalcemic rats. 22 We assume that primary CPPs are the predominant form that can be isolated from freshly drawn blood 19 and that their occurrence reflects imminent or active ongoing pathologic calcification.…”

Section: Discussionmentioning

confidence: 94%

Nanoparticle-Based Test Measures Overall Propensity for Calcification in Serum

Pasch

Farese

Gräber

et al. 2012

Journal of the American Society of Nephrology

267

351

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Vascular and soft tissue calcification contributes to cardiovascular morbidity and mortality in both the general population and CKD. Because calcium and phosphate serum concentrations are near supersaturation, the balance of inhibitors and promoters critically influences the development of calcification. An assay that measures the overall propensity for calcification to occur in serum may have clinical use. Here, we describe a nanoparticle-based assay that detects, in the presence of artificially elevated calcium and phosphate concentrations, the spontaneous transformation of spherical colloidal primary calciprotein particles (CPPs) to elongate crystalline secondary CPPs. We used characteristics of this transition to describe the intrinsic capacity of serum to inhibit the precipitation of calcium and phosphate. Using this assay, we found that both the sera of mice deficient in fetuin-A, a serum protein that inhibits calcification, and the sera of patients on hemodialysis have reduced intrinsic properties to inhibit calcification. In summary, we developed a nanoparticle-based test that measures the overall propensity for calcification in serum. The clinical use of the test requires evaluation in a prospective study.

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Section: Discussionmentioning

confidence: 94%

Nanoparticle-Based Test Measures Overall Propensity for Calcification in Serum

Pasch

Farese

Gräber

et al. 2012

Journal of the American Society of Nephrology

267

351

View full text Add to dashboard Cite

show abstract

“…The levels of CPPs are related to inflammation (22,37), and secondary CPPs induce an inflammatory response when exposed to macrophages in vitro (38). An unexpected crude association between parathyroid hormone and T 50 and, similarly, between ionized calcium and T 50 may be related to tertiary hyperparathyroidism causing (relative) hypercalcemia.…”

Section: Discussionmentioning

confidence: 99%

Serum Calcification Propensity Is a Strong and Independent Determinant of Cardiac and All-Cause Mortality in Kidney Transplant Recipients

Dahle

Åsberg

Hartmann

et al. 2016

American Journal of Transplantation

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“…Therefore, fetuin A has dual inhibitory actions, one in circulation and the other in vascular walls. The levels of fetuin A are reduced in dialysis patients, and it might reflect the excessive CPP formation in dialysis patients [37][38][39][40].…”

Section: Inhibitory Factors (With Comment About the Risk Of Warfarin mentioning

confidence: 99%

Impact of vascular calcification on cardiovascular mortality in hemodialysis patients: clinical significance, mechanisms and possible strategies for treatment

Ohtake

Kobayashi

2017

Ren Replace Ther

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Vascular calcification has now been recognized as a major problem in dialysis patients because of its strong influence on the prognosis. Along with the regulatory failure of calcification-inhibitory system, active phenotypic change of vascular smooth muscle cells (VSMCs) to osteoblast-like cells is also involved in the progression of vascular calcification. Delaying or improving the vascular calcification is thought to be very important to improve the cardiovascular mortality in dialysis patients. Several interventional trials against vascular calcification using non-calcium-containing phosphate binders, low-dose active vitamin D plus cinacalcet, modification of dialysate calcium concentration, and sodium thiosulfate have been done, and some trials including non-calcium-containing phosphate binders showed beneficial effect on delaying vascular calcification in dialysis patients. However, delaying or improving vascular calcification has not been clearly proved to result in improved cardiovascular event and/or mortality rate by prospective interventional randomized controlled trials in dialysis patients. Whether the improvement of vascular calcification could directly lead to the improvement of survival is an urgent issue of clinical trials in dialysis patients.

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Phosphorylated fetuin-A-containing calciprotein particles are associated with aortic stiffness and a procalcific milieu in patients with pre-dialysis CKD

Abstract: Increased CPP fetuin-A levels reflect an increasingly procalcific milieu and are associated with increased aortic stiffness in patients with pre-dialysis CKD.

Cited by 159 publications

References 66 publications

Nanoparticle-Based Test Measures Overall Propensity for Calcification in Serum

Nanoparticle-Based Test Measures Overall Propensity for Calcification in Serum

Serum Calcification Propensity Is a Strong and Independent Determinant of Cardiac and All-Cause Mortality in Kidney Transplant Recipients

Impact of vascular calcification on cardiovascular mortality in hemodialysis patients: clinical significance, mechanisms and possible strategies for treatment

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