Newly Developed Rat Model of Chronic Kidney Disease-Mineral Bone Disorder.

Abstract

AIM:

Chronic kidney disease-mineral bone disorder (CKD-MBD) is associated with all-cause and cardiovascular morbidity and mortality in patients with CKD. Thus, elucidating its pathophysiological mechanisms is essential for improving the prognosis. We evaluated characteristics of CKD-MBD in a newly developed CKD rat model.

METHODS:

We used male Sprague-Dawley (SD) rats and spontaneously diabetic Torii (SDT) rats, which are used as models for nonobese type 2 diabetes. CKD was induced by 5/6 nephrectomy (Nx). At 10 weeks, the rats were classified into six groups and administered with a vehicle or a low- or high-dose paricalcitol thrice a week. At 20 weeks, the rats were sacrificed; blood and urinary biochemical analyses and histological analysis of the aorta were performed.

RESULTS:

At 20 weeks, hemoglobin A1c (HbA1c) levels, blood pressure, and renal function were not significantly different among the six groups. Serum calcium and phosphate levels tended to be higher in SDT-Nx rats than in SD-Nx rats. The urinary excretion of calcium and phosphate was significantly greater in SDT-Nx rats than in SD-Nx rats. After administering paricalcitol, serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels were significantly higher in SDT-Nx rats than in SD-Nx rats. The degree of aortic calcification was significantly more severe and the aortic calcium content was significantly greater in SDT-Nx rats than in SD-Nx rats.

CONCLUSIONS:

We suggest that our new CKD rat model using SDT rats represents a useful CKD-MBD model, and this model was greatly influenced by paricalcitol administration. Further studies are needed to clarify the detailed mechanisms underlying this model.

• Authors: Kentaro Watanabe, Hideki Fujii, Shunsuke Goto, Kentaro Nakai, Keiji Kono, Shuhei Watanabe, Masami Shinohara, Shinichi Nishi
• Journal: Journal of atherosclerosis and thrombosis (J Atheroscler Thromb) Vol. 25 Issue 2 Pg. 170-177 (Feb 01 2018) ISSN: 1880-3873 [Electronic] Japan
• PMID: 28674323 (Publication Type: Journal Article)

Topics

• Animals
• Blood Pressure
• Chronic Kidney Disease-Mineral and Bone Disorder (etiology, metabolism, pathology)
• Diabetes Mellitus, Type 2 (complications)
• Disease Models, Animal
• Male
• Rats
• Rats, Sprague-Dawley
• Vascular Calcification