Abstract: TH-PO1056

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

Session Information

Category: Mineral Disease

  • 1201 Mineral Disease: Ca/Mg/PO4

Authors

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

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
PO4 DietPO4 (mM)Ca (mM)PTH (ng/ml)FGF23 (ng/ml)
0.52.2±0.32.6±0.30.41±0.183.1±2.7
1.05.0 ±1.02.2±0.12.4 ±1.347±18
1.55.8 ±1.42.0±.13.1 ±0.635 ±17

Funding

  • Commercial Support