title: The role of bone in CKD-mediated mineral and vascular disease.
abstract: Cardiovascular disease is the leading cause of death in pediatric patients with chronic kidney disease (CKD), and vascular calcifications start early in the course of CKD. Based on the growing body of evidence that alterations of bone and mineral metabolism and the therapies designed to treat the skeletal consequences of CKD are linked to cardiovascular calcifications, the Kidney Disease, Improving Global Outcomes (KDIGO) working group redefined renal osteodystrophy as a systemic disorder of mineral and bone metabolism due to CKD, and this newly defined disorder is now known as "chronic kidney disease-mineral bone disorder (CKD-MBD)". Elevated fibroblast growth factor 23 (FGF23), a bone-derived protein, is the first biochemical abnormality to be associated with CKD-MBD, and high FGF23 levels correlate with increased cardiovascular morbidity and mortality, suggesting that bone is central to both initiating and perpetuating the abnormal mineral metabolism and vascular disease in CKD. The current standard therapies for CKD-MBD affect FGF23 levels differently; non-calcium-based binders with or without concurrent use of dietary phosphate restriction reduce FGF23 levels, while calcium-based binders seem to either increase or have no effect on FGF23 levels. Active vitamin D sterols increase FGF23 levels, whereas therapy with calcimimetics decreases FGF23 levels. Thus, the appropriate therapy that will minimize the rise in FGF23 and prevent cardiovascular morbidity remains to be defined.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Khouzam
authors.forename: Katherine
authors.initials: K
authors.lastname: Wesseling-Perry
authors.forename: Isidro B
authors.initials: IB
authors.lastname: Salusky
mesh_terms: D001851:Bone Diseases, Metabolic / Q000150:complications / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D002648:Child; D019468:Disease Management; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism / Q000628:therapy; D061205:Vascular Calcification / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23