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Abstract: SA-PO007

Quantifying Composition Changes in Serum Biomarkers of Vascular Calcification in CKD

Session Information

Category: Bioengineering

  • 400 Bioengineering

Authors

  • Pence, Isaac, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Reneau, James A., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Moe, Orson W., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background

Vascular calcification (VC) is a strong predictor of cardiovascular morbidity and mortality for chronic kidney disease (CKD). Cardiovascular disease (CVD) is the leading cause of death for patients with CKD worldwide. Despite its importance in CVD/CKD, there are no tools to noninvasively diagnose VC, monitor progression, or prognosticate outcomes. Calciprotein particles (CPPs) are circulating biological nanoparticles composed of minerals, lipids, and proteins, and represent a novel biomarker of CVD. When CKD disrupts serum mineral and protein balance, CPPs mature into pathogenic secondary CPPs, which initiate tissue calcification. Here, we present the development of a new technology to assess VC risk: Raman Trapping Analysis (RTA), a quantitative label-free optical technique, is used to quantify composition of healthy and uremic patient derived serum.

Methods

Serum collected from healthy and uremic patients was processed to isolate CPPs and initiator components. Size exclusion was used to separate soluble CPP constituents and incubation in FBS supplemented with Ca and PO4 was used to generate mature CPPs. The gel-filtration method using OsteoSence reporter was used to quantify CPP levels, and dynamic light scattering (DLS) and transmission electron microscopy (TEM) to assess particle size and morphology. RTA of CPPs was acquired during maturation (24 hr) and after incubation (72 hr). Particle spectra were analyzed to investigate compositional differences between disease groups and time points.

Results

Analysis validated the formation of secondary CPPs. DLS/TEM confirmed particle maturation, and the OsteoSense assay indicated increased CPP levels between uremic vs healthy samples. RTA obtained particle spectra from CPPs comprising Ca-PO4 mineral, lipid, and protein signatures. A spectral model of chemical constituents was developed, and signatures were extracted for further statistical analysis.

Conclusion

RTA is capable of noninvasive label-free chemical characterization of CPPs derived from patient serum and provides novel information regarding dynamic changes in the composition and heterogeneity of these biomarkers. Precise evaluation of these signatures may provide new insights into serum biomarkers that can differentiate innate mineralization propensity and prognosticate patient risk for VC.

Funding

  • NIDDK Support