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Abstract: FR-PO288

Calcitriol at Therapeutic Doses for SHPT Promotes Vascular Calcification in Experimental CKD

Session Information

Category: Mineral Disease

  • 1202 Mineral Disease: Vitamin D, PTH, FGF-23

Authors

  • Svajger, Bruno A., Queen's University, Kingston, Ontario, Canada
  • Pruss, Cynthia M., Queen's University, Kingston, Ontario, Canada
  • Laverty, Kimberly J., Queen's University, Kingston, Ontario, Canada
  • Zelt, Jason, None, Kingston, Ontario, Canada
  • Petkovich, Martin P., None, Kingston, Ontario, Canada
  • Holden, Rachel M., Queen's University, Kingston, Ontario, Canada
  • Adams, Michael A., Queen's University, Kingston, Ontario, Canada
Background

Vitamin D deficiency is common in CKD and leads to SHPT. Calcitriol (CAL) and active vitamin D analogs are often used to treat SHPT. CAL use has been associated with improved patient survival; however, it has also been linked with PTH over-suppression and increased risk of vascular calcification (VC). This study examined the effects of CAL dose frequency and magnitude on bone and mineral status (PTH, FGF23), endothelial function (von Willebrand Factor–VWF) and VC in experimental CKD.

Methods

CKD was induced by 0.25% dietary adenine in adult male Sprague-Dawley rats (n=42). At 4 weeks (W), CKD rats were divided into 4 groups and treated with CAL as follows: 0ng/kg (CKD control (Ctl), n=8), 5ng/kg QID (therapeutic dose divided, n=9), 20ng/kg SID (therapeutic dose, n=8), 20ng/kg QID (high dose divided, n=9), or 80ng/kg SID (high dose, n=8). After 3W treatment, rats were sacrificed, tissues and blood were collected and assessed for VC, PTH, FGF-23, and VWF.

Results

PTH therapeutic target levels (2-9x control) were achieved at some point during all CAL treatments. After 1W treatment, both 20 and 80ng/kg/day reduced PTH (-72%) relative to CKD Ctl (p<0.05). However, at 3W, CAL-induced PTH suppression was less effective (-41%). At 3W, PTH suppression (-55% vs -29%) and FGF-23 elevation (20x vs 10x) was greater in 80ng/kg/day compared to 20ng/kg/day (p<0.05). Increased serum calcium (+40%) and VC (94% vs 29%) was evident in all CAL treatments vs CKD Ctl (p<0.05), and VWF was significantly elevated in CAL treatment groups vs CKD Ctl at 1W (2x, p<0.05) and 3W(1.5x, p<0.05). Sub-analysis showed PTH suppression status (therapeutic, over-suppressed, no response) did not alter negative outcomes (FGF-23, VC).

Conclusion

CAL suppressed PTH as expected although the suppression effect was attenuated over time. All CAL treatment groups exhibited similar increases in FGF-23, VC, and endothelial dysfunction independent of dosing regimen. Importantly, mineral bone disorder occurrence was not corrected regardless of calcitriol treatment success (based on PTH response).

Funding

  • Commercial Support