Kidney Week

Abstract: TH-PO1056

Transition from Low to High Dietary Phosphate Reduces Serum Calcium but Increases Vascular Calcification in Experimental CKD

Session Information

• Mineral Disease: Ca/Mg/PO4
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Mineral Disease

• 1201 Mineral Disease: Ca/Mg/PO4

Authors

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

Cynthia M. Pruss,

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

Kimberly J. Laverty,

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

Emilie C. Ward,

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

Bruno A. Svajger,

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

Paul S. Jeronimo,

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

Mandy E. Turner,

• 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

Chronic kidney disease (CKD) impairs phosphate (PO₄) homeostasis resulting in hyperphosphatemia, which is associated with cardiovascular events and vascular calcification (VC). Animal models of CKD demonstrate pathologies and outcomes similar to those of CKD patients. We examined the impact of dietary phosphate loading on markers of mineral metabolism in controlled adenine-induced CKD.

Methods

Sprague Dawley rats were fed a 0.25% adenine, 0.5% PO₄ diet for 4-5 weeks to induce stable CKD (creatinine >250 uM) , then fed 0.5% PO₄ diet without adenine. At 5.5 weeks, rats were fed either s 0.5%, 1% or 1.5% PO₄ diet, N=9, 10, 6, while another group (N=21) was fed increasing dietary PO₄ every 4 days (0.5%→0.75%→1%→1.5%). Controls were fed 0.5% PO₄ diet (N=8). Serum calcium (Ca), PO₄, FGF-23, PTH, and tissue Ca and PO₄ were determined.

Results

At 5 weeks, CKD rats vs control had 3.2±0.6 vs 2.5±0.3 mM PO₄ and 2.8±0.2 vs 2.4±0.1 mM Ca. Off adenine, the 0.5% group was at control PO₄ levels but had elevated Ca at 6.5 weeks. At 7 weeks, the 1.0 and 1.5% groups had marked increases in PO₄, PTH, and FGF-23, while serum Ca dropped (table 1). VC was observed in 80% of high PO₄ rats (1 or 1.5%). In the increasing dietary PO₄ group, serum PO₄ (mM) increased with dietary PO₄: baseline(2.1±.3), 0.5%(2.7±0.7), 1%(4.2±0.5), 1.5%(4.8±1.3) PO₄. Fasting serum Ca (mM) increased in CKD rats given 0.5% PO₄ (2.1±0.2→3.1±0.3), but significantly declined when fed 1%(2.4±0.7) and 1.5%(2.2±0.9) dietary PO₄. PTH and FGF-23 both increased (4x, 2x) with the increased dietary PO₄ and VC was observed in all rats.

Conclusion

In our CKD model, 0.5% PO₄ diet increased serum Ca but did not induce VC. In contrast, dietary PO₄ of 1% or more led to significant decreases in serum Ca, but generated high serum PO₄, FGF-23, PTH and VC. These findings uncover a new link between dietary PO₄ and serum Ca.

Rat Serum Levels at 7 Weeks

Funding

• Commercial Support –