title: A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease.
abstract: BACKGROUND
  Klotho was originally identified in a mutant mouse strain unable to express the gene that consequently showed shortened life spans. In humans, low serum Klotho levels are related to the prevalence of cardiovascular diseases in community-dwelling adults. However, it is unclear whether the serum Klotho levels are associated with signs of vascular dysfunction such as arterial stiffness, a major determinant of prognosis, in human subjects with chronic kidney disease (CKD).
  
  
  METHODS
  We determined the levels of serum soluble Klotho in 114 patients with CKD using ELISA and investigated the relationship between the level of Klotho and markers of CKD-mineral and bone disorder (CKD-MBD) and various types of vascular dysfunction, including flow-mediated dilatation, a marker of endothelial dysfunction, ankle-brachial pulse wave velocity (baPWV), a marker of arterial stiffness, intima-media thickness (IMT), a marker of atherosclerosis, and the aortic calcification index (ACI), a marker of vascular calcification.
  
  
  RESULTS
  The serum Klotho level significantly correlated with the 1,25-dihydroxyvitamin D level and inversely correlated with the parathyroid hormone level and the fractional excretion of phosphate. There were significant decreases in serum Klotho in patients with arterial stiffness defined as baPWV≥1400 cm/sec, atherosclerosis defined as maximum IMT≥1.1 mm and vascular calcification scores of ACI>0%. The serum Klotho level was a significant determinant of arterial stiffness, but not endothelial dysfunction, atherosclerosis or vascular calcification, in the multivariate analysis in either metabolic model, the CKD model or the CKD-MBD model. The adjusted odds ratio of serum Klotho for the baPWV was 0.60 (p = 0.0075).
  
  
  CONCLUSIONS
  Decreases in the serum soluble Klotho levels are independently associated with signs of vascular dysfunction such as arterial stiffness in patients with CKD. Further research exploring whether therapeutic approaches to maintain or elevate the Klotho level could improve arterial stiffness in CKD patients is warranted.
authors: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Masashi
authors: M
authors: Kitagawa
authors: Hitoshi
authors: H
authors: Sugiyama
authors: Hiroshi
authors: H
authors: Morinaga
authors: Tatsuyuki
authors: T
authors: Inoue
authors: Keiichi
authors: K
authors: Takiue
authors: Ayu
authors: A
authors: Ogawa
authors: Toshio
authors: T
authors: Yamanari
authors: Yoko
authors: Y
authors: Kikumoto
authors: Haruhito Adam
authors: HA
authors: Uchida
authors: Shinji
authors: S
authors: Kitamura
authors: Yohei
authors: Y
authors: Maeshima
authors: Kazufumi
authors: K
authors: Nakamura
authors: Hiroshi
authors: H
authors: Ito
authors: Hirofumi
authors: H
authors: Makino
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005260:Female; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D063177:Pulse Wave Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology; D012307:Risk Factors; D061205:Vascular Calcification / Q000097:blood; D059289:Vascular Stiffness
chemical_list: D015415:Biomarkers; D005966:Glucuronidase; D000090265:Klotho Proteins