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Abstract: FR-PO482

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

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Pruss, Cynthia M., Queen's University, Kingston, Ontario, Canada
  • Jeronimo, Paul S., Queen's University, Kingston, Ontario, Canada
  • Laverty, Kimberly J., Queen's University, Kingston, Ontario, Canada
  • Ward, Emilie C., Queen's University, Kingston, Ontario, Canada
  • Turner, Mandy E., Queen's University, Kingston, Ontario, Canada
  • Svajger, Bruno A., Queen's University, Kingston, Ontario, Canada
  • Petkovich, Martin P., Queen's University, Kingston, Ontario, Canada
  • Holden, Rachel M., Queen's University, Kingston, Ontario, Canada
  • Adams, Michael A., Queen's University, Kingston, Ontario, Canada
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