Kidney Week

Abstract: SA-PO251

An Oral Phosphate Challenge in Experimental CKD Reveals the Scope of Deficit in Calciprotein-Based Mineral Buffering Only If Both OsteoSense and T50 Are Used

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

• Fernandes, Eric Brian Peter, Queen's University, Kingston, Ontario, Canada

Eric Brian Peter Fernandes, BHSc

• Rowsell, Tyler, Queen's University, Kingston, Ontario, Canada

Tyler Rowsell, MSc

• Turner, Mandy E., Queen's University, Kingston, Ontario, Canada

Mandy E. Turner, PhD

• Holden, Rachel M., Queen's University, Kingston, Ontario, Canada

Rachel M. Holden, MD

• Adams, Michael A., Queen's University, Kingston, Ontario, Canada

Michael A. Adams, PhD

Background

In chronic kidney disease (CKD), disturbed phosphate (PO₄) homeostasis is linked to morbidity and mortality. Fetuin-based calciprotein particles (CPPs) are key to mineral buffering yet their role in health and disease is unclear. This study characterized the phenotype of CPPs in response to acute oral PO₄ challenges in both health and experimental CKD using a multi-modal approach.

Methods

CPPs were profiled in male Sprague-Dawley rats before and after CKD induction (n=10, 0.25% adenine, 6wks). After collecting fasted serum, animals rapidly ate a 1% PO₄ diet (10g, TD.08670) with serum collected at 2 and 6hrs. Serum minerals and OsteoSense detectable CPPs (OS-CPPs) were measured throughout, while type II CPP formation was assessed at 0 and 6hrs via T50 following an ex vivo mineral challenge. To contextualize OS-CPP observations, changes in OS-CPP detection versus in vitro T50-based CPP synthesis were compared. All differences stated are p<0.05.

Results

In CKD, both serum [PO₄] and total OS-CPPs increased by 12% at 2hrs post-challenge and by 30% and 16.6% at 6hrs. In contrast, in healthy rats at 2hrs, serum [PO₄] decreased (-8.7%) and OS-CPPs were elevated (11.5%), though by 6hrs no significant differences remained. Low-density OS-CPPs were much more prevalent than high-density forms in CKD (93±1%) vs healthy (56±8%) across all time points. The overall OS-CPP profile also revealed type II CPPs are poorly detected by OS. The T50 time was decreased in CKD rats (19%) vs healthy (6%) after mineral challenge.

Conclusion

The CPP profile in fasted rats showed near saturation of mineral buffering in experimental CKD as detected by the OS-CPP profile, but not by T50. The acute oral mineral challenge further revealed this near saturation of CPPs via a marked reduction in the T50 time. Given the issues regarding the detection of different forms of CPPs, these findings emphasize the critical need to use multiple protocols to properly evaluate changes in the CPP-based mineral buffering system.