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Early chronic kidney disease-mineral bone disorder stimulates vascular calcification.
Kidney Int. 2014 Jan; 85(1):142-50.KI

Abstract

The chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome is an extremely important complication of kidney diseases. Here we tested whether CKD-MBD causes vascular calcification in early kidney failure by developing a mouse model of early CKD in a background of atherosclerosis-stimulated arterial calcification. CKD equivalent in glomerular filtration reduction to human CKD stage 2 stimulated early vascular calcification and inhibited the tissue expression of α-klotho (klotho) in the aorta. In addition, osteoblast transition in the aorta was stimulated by early CKD as shown by the expression of the critical transcription factor Runx2. The ligand associated with the klotho-fibroblast growth factor receptor complex, FGF23, was found to be expressed in the vascular media of sham-operated mice. Its expression was decreased in early CKD. Increased circulating levels of the osteocyte-secreted proteins, FGF23, and sclerostin may have been related to increased circulating klotho levels. Finally, we observed low-turnover bone disease with a reduction in bone formation rates more than bone resorption. Thus, the CKD-MBD, characterized by cardiovascular risk factors, vascular calcification, increased circulating klotho, FGF23 and sclerostin levels, and low-turnover renal osteodystrophy, was established in early CKD. Early CKD caused a reduction of vascular klotho, stimulated vascular osteoblastic transition, increased osteocytic secreted proteins, and inhibited skeletal modeling producing the CKD-MBD.

Authors+Show Affiliations

Division of Pediatric Nephrology, Department of Pediatrics, Washington University, St Louis, Missouri, USA.Division of Pediatric Nephrology, Department of Pediatrics, Washington University, St Louis, Missouri, USA.Division of Pediatric Nephrology, Department of Pediatrics, Washington University, St Louis, Missouri, USA.Division of Nephrology, Department of Medicine, University of Kentucky, Lexington, Kentucky, USA.Division of Nephrology, Department of Medicine, University of Kentucky, Lexington, Kentucky, USA.Division of Pediatric Nephrology, Department of Pediatrics, Washington University, St Louis, Missouri, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23884339

Citation

Fang, Yifu, et al. "Early Chronic Kidney Disease-mineral Bone Disorder Stimulates Vascular Calcification." Kidney International, vol. 85, no. 1, 2014, pp. 142-50.
Fang Y, Ginsberg C, Sugatani T, et al. Early chronic kidney disease-mineral bone disorder stimulates vascular calcification. Kidney Int. 2014;85(1):142-50.
Fang, Y., Ginsberg, C., Sugatani, T., Monier-Faugere, M. C., Malluche, H., & Hruska, K. A. (2014). Early chronic kidney disease-mineral bone disorder stimulates vascular calcification. Kidney International, 85(1), 142-50. https://doi.org/10.1038/ki.2013.271
Fang Y, et al. Early Chronic Kidney Disease-mineral Bone Disorder Stimulates Vascular Calcification. Kidney Int. 2014;85(1):142-50. PubMed PMID: 23884339.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Early chronic kidney disease-mineral bone disorder stimulates vascular calcification. AU - Fang,Yifu, AU - Ginsberg,Charles, AU - Sugatani,Toshifumi, AU - Monier-Faugere,Marie-Claude, AU - Malluche,Hartmut, AU - Hruska,Keith A, Y1 - 2013/07/24/ PY - 2013/01/24/received PY - 2013/05/09/revised PY - 2013/05/16/accepted PY - 2013/7/26/entrez PY - 2013/7/26/pubmed PY - 2014/9/30/medline SP - 142 EP - 50 JF - Kidney international JO - Kidney Int VL - 85 IS - 1 N2 - The chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome is an extremely important complication of kidney diseases. Here we tested whether CKD-MBD causes vascular calcification in early kidney failure by developing a mouse model of early CKD in a background of atherosclerosis-stimulated arterial calcification. CKD equivalent in glomerular filtration reduction to human CKD stage 2 stimulated early vascular calcification and inhibited the tissue expression of α-klotho (klotho) in the aorta. In addition, osteoblast transition in the aorta was stimulated by early CKD as shown by the expression of the critical transcription factor Runx2. The ligand associated with the klotho-fibroblast growth factor receptor complex, FGF23, was found to be expressed in the vascular media of sham-operated mice. Its expression was decreased in early CKD. Increased circulating levels of the osteocyte-secreted proteins, FGF23, and sclerostin may have been related to increased circulating klotho levels. Finally, we observed low-turnover bone disease with a reduction in bone formation rates more than bone resorption. Thus, the CKD-MBD, characterized by cardiovascular risk factors, vascular calcification, increased circulating klotho, FGF23 and sclerostin levels, and low-turnover renal osteodystrophy, was established in early CKD. Early CKD caused a reduction of vascular klotho, stimulated vascular osteoblastic transition, increased osteocytic secreted proteins, and inhibited skeletal modeling producing the CKD-MBD. SN - 1523-1755 UR - https://www.unboundmedicine.com/medline/citation/23884339/Early_chronic_kidney_disease_mineral_bone_disorder_stimulates_vascular_calcification_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(15)56139-5 DB - PRIME DP - Unbound Medicine ER -