Calcitriol combined with high‐calcium and high‐phosphorus diet induces vascular calcification model in chronic kidney disease rats

Abstract

AbstractBackgroundCardiovascular diseases represent a significant complication arising from chronic kidney disease (CKD). Vascular calcification is an important risk factor for cardiovascular diseases. Reducing vascular calcification is therefore critical to reducing mortality in CKD patients.HypothesisThis study aims to establish a vascular calcification model in rats with CKD by administering subcutaneous injections of calcitriol in combination with a high‐calcium and high‐phosphorus diet.MethodsThe rats were divided into the CKD vascular calcification model group (subtotal nephrectomy+ [SNx+]) and the sham‐operated control group (subtotal nephrectomy− [SNx−]). The rats in the SNx(+) group were administered high‐calcium and high‐phosphorus feeds following a 5/6 nephrectomy. Calcitriol (1 μg/kg, three times a week) was injected subcutaneously at weeks 0, 4, 8, and 12 after the operation. Measurements of body weight, urine, serum biochemical indicators and vascular calcification level were conducted in rats.Results(1) Compared with the SNx(−) group, rats in the SNx(+) group experienced an increase in 24‐h urine output, urinary phosphorus, and urinary microprotein excretion, along with the development of severe anemia. Additionally, there was a notable elevation in serum phosphorus, blood urea nitrogen, blood creatinine, fibroblast growth factor 23 (FGF‐23), and intact parathyroid hormone levels, accompanied by severe hypoproteinemia at week 12. (2) The results of micro‐compuyed tomography (μCT) and alizarin S staining of the thoracic aorta demonstrated an increase in vascular calcification in the SNx(+) group. (3) The expression levels of vascular calcification‐related proteins were increased.ConclusionsThe administration of calcitriol combined with a high‐calcium and high‐phosphorus diet was found to induce vascular calcification in CKD rats, leading to a disturbance in mineral metabolism. Vascular calcification was effectively induced in CKD rats after 12 weeks of modeling, thereby presenting a novel approach for establishing a vascular calcification model in CKD rats, helping to elucidate this clinical condition and its underlying molecular mechanisms.