title: Pathophysiology of the chronic kidney disease-mineral bone disorder.
abstract: OBJECTIVE
  The causes of excess cardiovascular mortality associated with chronic kidney disease (CKD) have been attributed in part to the CKD-mineral bone disorder syndrome (CKD-MBD), wherein, novel cardiovascular risk factors have been identified. The causes of the CKD-MBD are not well known and they will be discussed in this review
  
  
  RESULTS
  The discovery of WNT (portmanteau of wingless and int) inhibitors, especially Dickkopf 1, produced during renal repair and participating in the pathogenesis of the vascular and skeletal components of the CKD-MBD implied that additional pathogenic factors are critical, leading to the finding that activin A is a second renal repair factor circulating in increased levels during CKD. Activin A derives from peritubular myofibroblasts of diseased kidneys, where it stimulates fibrosis, and decreases tubular klotho expression. The type 2 activin A receptor, ActRIIA, is decreased by CKD in atherosclerotic aortas, specifically in vascular smooth muscle cells (VSMC). Inhibition of activin signaling by a ligand trap inhibited CKD induced VSMC dedifferentiation, osteogenic transition and atherosclerotic calcification. Inhibition of activin signaling in the kidney decreased renal fibrosis and proteinuria.
  
  
  CONCLUSIONS
  These studies demonstrate that circulating renal repair factors are causal for the CKD-MBD and CKD associated cardiovascular disease, and identify ActRIIA signaling as a therapeutic target in CKD that links progression of renal disease and vascular disease.
authors.affiliation: aDepartment of Pediatrics, Nephrology bDepartments of Medicine and Cell Biology Washington University Saint Louis, Saint Louis, Missouri cDepartment of Pediatrics, Nephrology, Southern Illinois University, Springfield, Illinois, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hruska
authors.forename: Michael
authors.initials: M
authors.lastname: Seifert
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Sugatani
mesh_terms: D000818:Animals; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D008903:Minerals / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000503:physiopathology*; D061205:Vascular Calcification / Q000503:physiopathology*
chemical_list: D008903:Minerals