Kidney Week

Abstract: FR-PO482

The Phosphate Binding Therapy Fermagate Attenuates Vascular Calcification in Experimental Adenine-Induced CKD

Session Information

• Bone and Mineral Metabolism: Basic
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 401 Bone and Mineral Metabolism: Basic

Authors

• Pruss, Cynthia M., Queen's University, Kingston, Ontario, Canada

Cynthia M. Pruss,

• Jeronimo, Paul S., Queen's University, Kingston, Ontario, Canada

Paul S. Jeronimo,

• Laverty, Kimberly J., Queen's University, Kingston, Ontario, Canada

Kimberly J. Laverty,

• Ward, Emilie C., Queen's University, Kingston, Ontario, Canada

Emilie C. Ward,

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

Mandy E. Turner,

• Svajger, Bruno A., Queen's University, Kingston, Ontario, Canada

Bruno A. Svajger,

• Petkovich, Martin P., Queen's University, Kingston, Ontario, Canada

Martin P. Petkovich,

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

Rachel M. Holden,

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

Michael A. Adams,

Background

Hyperphosphatemia, common in chronic kidney disease (CKD), is linked to vascular calcification (VC), which further increases cardiovascular risk. Some evidence suggests oral magnesium (Mg) inhibits VC. Fermagate is a calcium-free, magnesium-releasing phosphate binder that controls hyperphosphatemia. This study determined if fermagate treatment compared to untreated control could impact VC in the adenine-induced CKD rat model.

Methods

Male Sprague Dawley rats were fed a 0.25% adenine, 0.5% phosphate (PO₄) diet to induce CKD (creatinine >250 uM) over 4-5 weeks, then fed 0.5% PO₄ without adenine diet. At 6 weeks CKD, two dietary PO₄ regimens were tested: moderate PO₄ (0.75%P) diet (5g 8AM and 4PM ±fermagate (FER n=9) untreated control (CON n=6), 10g diet overnight, or a combination of high and low PO₄ (1-0.5%P): high (1%P 5g 8AM, 4PM ±fermagate) and 10g low (0.5%P) PO₄ diet overnight (FER n=8, CON n=10) with the same amount of daily dietary PO₄. Serum calcium (Ca), magnesium (Mg), PO₄, FGF-23, parathyroid hormone (PTH), vitamin D metabolome, and tissue Ca and PO₄ were determined.

Results

In both studies, fermagate increased serum Mg (203% 0.75%P, p<0.0001; 163% 0.5-1%P, p<0.0001, % control, 2-way ANOVA) and had lower levels of serum PO₄ (67% 0.75%P, p<0.001; 64% 0.5-1%P, p<0.001), and PTH (31% 0.75%P, p<0.001; 16% 0.5-1%P, p<0.001). The proportion of VC was significantly reduced in arterial tissues with fermagate treatment (79%/65% in CON vs. 35% FER(0.75%P) and 13% FER(0.5-1%P), respectively, p<0.001). This inhibition was also evident on a per animal basis (100%/70% CON had VC vs. 33% FER(0.75%P) and 13%(FER 0.5-1%P), p<0.05, respectively). Fermagate treatment did not significantly alter Mg levels in the vasculature tissue, serum Ca, FGF-23, or serum vitamin D metabolome.

Conclusion

These results demonstrate that fermagate effectively reduces the bioavailability of dietary PO₄, decreases serum PO₄, increases serum Mg, and effectively limits the development and progression of CKD-induced vascular calcification.

Funding

• Commercial Support –