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Abstract: TH-PO546

ASARM Peptide Reverses Hyperphosphatemia; Prevents Calciphylaxis-Like Lesions; and Corrects Renal, Bone, Brain, and Cardiovascular Calcification in a Rat Model of CKD

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Rowe, Peter S. N., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Stubbs, Jason R., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Yu, Alan S.L., University of Kansas Medical Center, Kansas City, Kansas, United States
  • McCarthy, Ellen T., University of Kansas Medical Center, Kansas City, Kansas, United States
Background

Abnormalities in mineral metabolism, bone and vascular calcification occur in Chronic Kidney Disease (CKD-MBD). Cognitive function also declines as the disease progresses. Bone ASARM peptides are strong inhibitors of mineralization and induce hypophosphatemia by inhibiting phosphate uptake from the gut. We hypothesize treatment of CKD-MBD rats with ASARM peptides will reverse hyperphosphatemia, correct mineralization defects and improve mortality.

Methods

To test our hypothesis, we used a rat 5/6 Nephrectomy experimental model (NEPHREX) and sham operated rats (SHAM) as controls. Male rats (16 wk, 250 gm) were fed a high phosphate diet to worsen mineral metabolism defects (2% P, 2000 IU Vit D and 0.8% Ca; TEKLAD 170496). ASARM peptide was infused continuously for 4 weeks using subcutaneous implantation of Alzet osmotic pumps. Sera collections were taken at the beginning and end of the study.

Results

NEPHREX rats treated with ASARM-peptide showed major reductions in hyperphosphatemia, and improved renal, bone, brain and cardiovascular calcification compared to controls treated with vehicle (Figure 1). Also, the high phosphate diet NEPHREX rats developed sub-dermal medial blood vessel calcification and calciphylaxis like lesions. The subdermal blood vessel calcifications did not occur in 56-NEPHREX rats treated with ASARM-peptide.

Conclusion

In summary our study shows ASARM peptides infused into a rat model with CKD corrects hyperphosphatemia and improves bone and renal mineralization abnormalities. These findings also confirm our hypothesis and supports the utility of ASARM peptide treatment in patients with CKD-MBD.

Figure 1: ASARM peptide corrects CKD-MBD mineralization abnormalities as measured using μCT: A. Heart, B. Cortical femur diaphysis, C. Skin, and D. graphical representation of MV/TV (mineral volume/total volume) and BV/TV (Bone /Total volume).

Funding

  • NIDDK Support