Association between amorphous calcium-phosphate ratios in circulating calciprotein particles and prognostic biomarkers in hemodialysis patients

Abstract

Calciprotein particles (CPPs) are circulating colloidal mineral-protein complexes containing crystalline and/or non-crystalline (amorphous) calcium-phosphate (CaPi). Serum CPP levels correlate with vascular stiffness and calcification in patients with chronic kidney disease (CKD). In vitro studies showed that CPPs containing crystalline CaPi were more arteriosclerogenic and inflammogenic than CPPs without containing crystalline CaPi. Thus, we hypothesized that not only the quantity but also the quality of CPPs (the phase of CaPi) might affect clinical outcomes. To test this hypothesis, we quantified amorphous CaPi ratio defined as the ratio of the amorphous CaPi amount to the total CaPi amount in serum CPPs from 183 hemodialysis patients and explored its possible correlation with serum parameters associated with prognosis of hemodialysis patients. Multivariate analysis revealed that the amorphous CaPi ratio correlated positively with hemoglobin and negatively with fibroblast growth factor-21 (FGF21), which remained significant after adjusting for the total CaPi amount. Because low hemoglobin and high FGF21 are associated with increased mortality, the present study warrants further studies to determine whether low amorphous CaPi ratio in circulating CPPs may be associated with poor prognosis in hemodialysis patients.

Association of calciprotein particles with serum phosphorus among patients undergoing conventional and extended-hours haemodialysis

“…Multivariate analysis showed a stronger effect of phosphorus on plasma CPP (CPP-II) and serum CPP (CPP-I + II) than calcium, and the relationship between CPP and phosphorus levels differed among HD groups. Plasma CPP (CPP-II) levels, which have pathogenic activity by inducing calcification and immune responses [ 14 ], increased more gradually with increasing phosphorus levels in the extended-hours HD group than in the conventional HD group. These results suggest that phosphorus-induced vascular calcification is less likely to occur in patients on extended-hours HD, which may partially explain their favourable clinical outcomes.…”

“…In contrast, CPP levels in serum samples represent total CPP levels (CPP-I and CPP-II) because blood coagulation accelerates the amorphous-to-crystalline phase transition of CaPi in CPP-I (Fig. 1 ) [ 14 , 25 ].…”

Chronic Kidney Disease with Mineral Bone Disorder and Vascular Calcification: An Overview

“…CPPs, as already mentioned, can be distinguished in two sequential forms: primary CPPs, small complexes of amorphous calcium phosphate, and secondary CPPs, containing a needle-shaped crystallized complex of calcium phosphate [ 135 ]. CPPs’ serum levels increase CKD progression [ 136 ]. A recently developed in vitro assay can identify the propensity of VC formation and overall calcification by measuring the semi maximal conversion time (T50, in minutes) from primary to secondary CPPs when given additional calcium and phosphate [ 137 ].…”

Small organic molecules containing amorphous calcium phosphate: synthesis, characterization and transformation

“…Considering this, numerous attempts have been undertaken in the development of ACP composite materials using macromolecules such as osteopontin, osteocalcin, dentin matrix protein, bone sialoprotein, dentin phosphoprotein, matrix extracellular protein, connexin 43, casein phospho-peptide, α 2 HS-glycoproteins, fibrin, and albumin (Reynolds, 1998;Makowski and Ramsby, 2001;Gajjeraman et al, 2007;Yang et al, 2010;Yarbrough et al, 2010;Syed-Picard et al, 2013;Padovano et al, 2015;Zhao et al, 2018;Iline-Vul et al, 2020;Erceg and Dutour Sikirić, 2022;Nakamura et al, 2022;Indurkar et al, 2023a). However, Becher et al have identified that many biological ubiquitous small organic molecules can inhibit the conversion of ACP to HAp at their respective tissue concentration (Becker, 1977).…”