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- Title
Disturbances in Bone Largely Predict Aortic Calcification in an Alternative Rat Model Developed to Study Both Vascular and Bone Pathology in Chronic Kidney Disease.
- Authors
Neven, Ellen; Bashir-Dar, Rida; Dams, Geert; Behets, Geert J.; Verhulst, Anja; Elseviers, Monique; D'Haese, Patrick C.
- Abstract
Because current rat models used to study chronic kidney disease (CKD)-related vascular calcification show consistent but excessive vascular calcification and chaotic, immeasurable, bone mineralization due to excessive bone turnover, they are not suited to study the bone-vascular axis in one and the same animal. Because vascular calcification and bone mineralization are closely related to each other, an animal model in which both pathologies can be studied concomitantly is highly needed. CKD-related vascular calcification in rats was induced by a 0.25% adenine/low vitamin K diet. To follow vascular calcification and bone pathology over time, rats were killed at weeks 4,8,10,11,and 12. Both static and dynamic bone parameters were measured. Vascular calcification was quantified by histomorphometry and measurement of the arterial calcium content. Stable, severe CKD was induced along with hyper-phosphatemia, hypocalcemia as well as increased serum PTH and FGF23. Calcification in the aorta and peripheral arteries was present from week 8 of CKD onward. Four and 8 weeks after CKD, static and dynamic bone parameters were measurable in all animals, thereby presenting typical features of hyperparathyroid bone disease. Multiple regression analysis showed that the eroded perimeter and mineral apposition rate in the bone were strong predictors for aortic calcification. This rat model presents a stable CKD, moderate vascular calcification, and quantifiable bone pathology after 8 weeks of CKD and is the first model that lends itself to study these main complications simultaneously in CKD in mechanistic and intervention studies.
- Subjects
CALCIFICATION; CHRONIC kidney failure; BONE diseases; LABORATORY rats; HYPERPARATHYROIDISM; MULTIPLE regression analysis
- Publication
Journal of Bone & Mineral Research, 2015, Vol 30, Issue 12, p2313
- ISSN
0884-0431
- Publication type
Article
- DOI
10.1002/jbmr.2585