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Kidney Week

Abstract: TH-PO1059

Vessels Are an Important Depot for Phosphate in Response to an Oral Load in an Experimental Model of CKD

Session Information

Category: Mineral Disease

  • 1201 Mineral Disease: Ca/Mg/PO4

Authors

  • Turner, Mandy E., Queen's University, Kingston, Ontario, Canada
  • Jeronimo, Paul S., Queen's University, Kingston, Ontario, Canada
  • Ward, Emilie C., Queen's University, Kingston, Ontario, Canada
  • Laverty, Kimberly J., 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

Dysregulated phosphate (PO4) homeostasis contributes to increased cardiovascular risk in CKD patients, in part due to vascular calcification. We sought to determine if tissue deposition of PO4 following an oral PO4 load was altered by level of kidney function and changes in dietary PO4.

Methods

CKD was induced in rats using dietary adenine (0.25%, 0.5% PO4). At 6 weeks, adenine was stopped and animals were fed either low phosphate (LP) (0.5%, N=48) or high phosphate (HP) (1.0%, N=24) diet for 2 weeks. Non-CKD animals followed a parallel protocol (0.5%, N=12 and 1.0%, N=12). Prior to sacrifice, 6 hr fasted animals consumed 0.1g of PO4 spiked with ~5mil CPM of 33PO4. Blood samples were drawn at 20 min up to 6 hrs after the PO4 load for measurement of 33PO4 and phosphate. Animals were sacrificed at 0, 2, and 6 hrs post-oral load. Various tissues were collected for radioactivity and PO4 measurement.

Results

The pattern of tissue disposition of PO4 was altered by kidney function and pre-existing level of dietary PO4. An HP diet produced a greater increase in serum PO4, parathyroid hormone and fibroblast growth factor 23 than the LP diet. Serum 33PO4 was detectable within 20 min following the oral load. In control animals, vascular tissue levels of 33PO4 fell between 2 hrs and 6 hrs indicating lack of retention. In contrast, in CKD rats, vascular tissue levels of 33PO4 were markedly higher at 6 hrs compared to 2 hrs, indicating substantial accrual and retention of phosphate. Although both bone and blood vessels had greater phosphate accrual in CKD, only the HP diet induced a vascular-selective deposition. That is, the vascular tissue:bone ratio was more than twice that found in either controls or LP CKD (bone:vessel CPM, 2hr: 1.7±0.8 vs. 0.6±0.2, p=0.003; 6hr: 1.2±0.9 vs. 0.4±0.1, p=0.008). CKD rats exposed to the HP diet had higher levels of phosphate in arteries compared to the LP diet (74±176 v. 715±624 nmol/mg of tissue, p<0.0001) consistent with more severe vascular calcification.

Conclusion

Changing from an LP to a HP diet in experimental CKD produces maladaptive responses in vascular tissue resulting in preferential and sustained vascular deposition of phosphate that likely associates with the vascular calcification phenotype.

Funding

  • Government Support - Non-U.S.