Kidney Week

Abstract: SA-PO249

Calciprotein Particles (CPPs) Are Cleared Predominantly by Liver, Spleen, and Bone in a Rat Model of CKD

Session Information

• CKD-MBD: Basic and Translational
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 501 Bone and Mineral Metabolism: Basic

Authors

• De Baaij, Jeroen H.F., Radboud Universitair Medisch Centrum, Nijmegen, Netherlands

Jeroen H.F. De Baaij, PhD

• Zeper, Lara W., Radboud Universitair Medisch Centrum, Nijmegen, Netherlands

Lara W. Zeper, MS

• Leermakers, Pieter A., Radboud Universitair Medisch Centrum, Nijmegen, Netherlands

Pieter A. Leermakers, PhD

• Bos, Caro, Radboud Universitair Medisch Centrum, Nijmegen, Netherlands

Caro Bos

• Hoenderop, Joost, Radboud Universitair Medisch Centrum, Nijmegen, Netherlands

Joost Hoenderop, PhD

Background

Calciprotein particles (CPPs) provide an efficient mineral buffering system to prevent the complexation of phosphate and calcium in the circulation. However, in chronic kidney disease (CKD), the phosphate load exceeds the mineral buffering capacity, resulting in the formation of crystalline CPP2 particles. CPP2 have been associated with cardiovascular events and mortality. Moreover, CPP2 have been demonstrated to induce calcification in vitro. In this study, we examined the fate of CPP2 in a rat model of CKD.

Methods

Calcification was induced in Sprague Dawley rats by a 5/6-nephrectomy (5/6-Nx) combined with a high phosphate diet. Control rats received a sham surgery and high phosphate diet. Twelve weeks after surgery kidney failure was significantly induced in 5/6-Nx rats as determined by enhanced creatinine and urea plasma levels and abnormal kidney histological architecture. Subsequently, radioactive and fluorescent (FITC)-labeled CPP2 ([⁸⁹Zr]Zr-CPP2-FITC) were injected i.v. to determine clearance in vivo.

Results

Using positron emission tomography scans and radioactive biodistribution measurements, it was demonstrated that [⁸⁹Zr]Zr-CPP2-FITC are mainly present in the liver, spleen, and bones in both 5/6-Nx and sham rats. Immunohistochemistry showed that [⁸⁹Zr]Zr-CPP2-FITC are predominantly taken up by Kupffer cells and macrophages. However, [⁸⁹Zr]Zr-CPP2-FITC could also be detected in hepatocytes. In the different parts of the aorta and in the blood, low values of [⁸⁹Zr]Zr-CPP2-FITC were detectable, independent of the presence of calcification.

Conclusion

CPP2 are cleared rapidly from the circulation by the liver, bones, and spleen in a rat model of CKD. In the liver, Kupffer cells, macrophages, and hepatocytes contribute to CPP2 clearance. Our results suggest that targeting liver CPP clearance may reduce the burden of crystalline CPP in the development of vascular calcification.