title: Nanoparticle-based test measures overall propensity for calcification in serum.
abstract: 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.
authors.affiliation: Department of Nephrology and Hypertension, University Hospital and University of Bern, Inselspital, 3010 Bern, Switzerland. andreas.pasch@insel.ch
authors.forename: Andreas
authors.initials: A
authors.lastname: Pasch
authors.forename: Stefan
authors.initials: S
authors.lastname: Farese
authors.forename: Steffen
authors.initials: S
authors.lastname: Gräber
authors.forename: Johanna
authors.initials: J
authors.lastname: Wald
authors.forename: Walter
authors.initials: W
authors.lastname: Richtering
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.forename: Willi
authors.initials: W
authors.lastname: Jahnen-Dechent
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000097:blood*; D002118:Calcium / Q000097:blood*; D016022:Case-Control Studies; D011232:Chemical Precipitation; D003102:Colloids; D003460:Crystallization; D006801:Humans; D008027:Light; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D053758:Nanoparticles; D036103:Nanotechnology / Q000379:methods*; D009391:Nephelometry and Turbidimetry; D010710:Phosphates / Q000097:blood; D006435:Renal Dialysis; D012542:Scattering, Radiation; D012995:Solubility; D060749:alpha-2-HS-Glycoprotein / Q000172:deficiency / Q000235:genetics
chemical_list: C556357:Ahsg protein, mouse; D003102:Colloids; D010710:Phosphates; D060749:alpha-2-HS-Glycoprotein; D002118:Calcium