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.
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 hyperphosphatemia, 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.
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Neven
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Belgium.
authors.forename: Rida
authors.initials: R
authors.lastname: Bashir-Dar
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Dams
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Belgium.
authors.forename: Geert J
authors.initials: GJ
authors.lastname: Behets
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Belgium.
authors.forename: Anja
authors.initials: A
authors.lastname: Verhulst
authors.affiliation: Department of Nursing Sciences, Faculty of Medicine and Public Health, University of Antwerp, Belgium.
authors.forename: Monique
authors.initials: M
authors.lastname: Elseviers
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Belgium.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: D'Haese
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology*; D016723:Bone Remodeling; D001842:Bone and Bones / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006934:Hypercalcemia / Q000097:blood; D054559:Hyperphosphatemia / Q000097:blood; D008297:Male; D010012:Osteogenesis; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D061205:Vascular Calcification / Q000503:physiopathology*; D014812:Vitamin K / Q000378:metabolism
chemical_list: C505605:Fgf23 protein, rat; D010281:Parathyroid Hormone; D014812:Vitamin K; D005346:Fibroblast Growth Factors
keywords: BONE DISEASE; CHRONIC KIDNEY DISEASE; MINERAL ABNORMALITIES; RAT MODEL; VASCULAR CALCIFICATION