Abstract: TH-PO0019
A Longitudinal Study on Uremic Vasculopathy and Calcification in Rats with CKD
Session Information
- Mineral Balance: Physiology and Pathophysiology
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 501 Bone and Mineral Metabolism: Basic
Authors
- El-Haj, Lama L., Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark
- Mace, Maria Lerche, Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark
- Hornum, Mads, Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark
- Nordholm, Anders, Herlev Hospital, Herlev, Capital Region of Denmark, Denmark
- Hansen, Ditte, Kobenhavns Universitet, Copenhagen, Capital Region of Denmark, Denmark
Background
The aim of the study is to characterize the induction and potential secretion of signal molecules from the vasculature in CKD and the association with the concomitant disturbed bone metabolism.
Methods
Male Wistar rats underwent 5/6 nephrectomy (n=24). The rats were fed a high 1.4% phosphorus diet from one week after surgery and treated with the active vitamin D analog alfacalcidol 80 ng intraperitoneally 3 times weekly from 8 weeks after surgery. To induce vascular calcification. All uremic rats were compared to age-matched normal controls, on standard diet (n=24). The rats were terminated after 4, 8, 10 and 14 weeks of uremia (n=8/control n=4). Plasma was collected and creatinine, urea, ionized calcium, phosphate and PTH were measured. The abdominal and thoracal aorta were removed. The aortic calcium content was measured and RNA sequencing performed. A subsection of the aorta was cut into 1mm aortic rings and placed in DMEM high glucose supplemented with 10% FBS and 1% P/S, and incubated ex vivo for 24 hours. The media was collected and the secretion of activin-A, sclerostin, and FGF-23 were analyzed by ELISA. Bone was analyzed by microCT.
Results
Plasma creatinine was significantly elevated in CKD rats. Aortic secretion of activin-A increased from 5992±351 pg/mL in controls to 13176±3094 pg/mL at week 8 (p<0.01), with a slightly decrease in week 10 CKD rats. Sclerostin secretion increased from 41.7±58.8 pg/mL in controls to 477±336 pg/mL at week 8 (p<0.05). FGF23 secretion increased from 0.5±1 in controls to 223,1±318 in week 10 CKD rats. Aortic calcium content was significantly higher at week 10 (CKD rats; 0.125±0.079 mmol/L vs. 0.026±0.006 mmol/L; controls, p=0.034) compared to the control group, indicating active mineral deposition.
RNA sequencing analysis showed an early osteogenic transition and a highly varied gene expression along the progression of CKD.
Bone microCT showed no significant difference in trabecular TMD or bone volume, in the control groups compared to the CKD groups.
Conclusion
The present findings strengthen the hypothesis that the vascular calcification in CKD may induce an active secretion of endocrine factors from the vasculature, such as activin-A, sclerostin, and FGF-23. These may be of importance for the bone disease in CKD.