title: Soluble α-klotho and its relation to kidney function and fibroblast growth factor-23.
abstract: BACKGROUND
  Relations between fibroblast growth factor-23 (FGF-23), soluble α-klotho (s-α-klotho), and kidney function in chronic kidney disease (CKD) are still unclear. Especially the role of s-α-klotho requires further study.
  
  
  OBJECTIVE
  Our objectives were to analyze the relation of s-α-klotho to estimated glomerular filtration rate (eGFR), FGF-23, and other parameters of calcium-phosphate metabolism and to investigate the response of s-α-klotho to cholecalciferol.
  
  
  METHODS
  Twenty-four CKD (stage 1-5) patients participated in this 8-week randomized controlled trial (vitamin D and chronic renal insufficiency).
  
  
  METHODS
  Interventions included 40 000 IU cholecalciferol or placebo weekly.
  
  
  METHODS
  S-α-klotho was determined by ELISA with antihuman klotho antibodies 67G3 and 91F1.
  
  
  RESULTS
  For all patients, s-α-klotho concentrations did not differ between CKD stages. When patients were subdivided based on FGF-23 concentrations, a positive association of s-α-klotho with eGFR became apparent in patients with lower than median FGF-23 concentrations but not in those above median value. Patients with s-α-klotho below 204 pg/mL showed higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase compared with patients with higher s-α-klotho. Treatment with cholecalciferol significantly increased 1,25-dihydroxyvitamin D. The increase of FGF-23 had only borderline significance. There was no significant effect of high-dose cholecalciferol administration for 8 weeks on plasma s-α-klotho.
  
  
  CONCLUSIONS
  CKD patients with s-α-klotho below 204 pg/mL had higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase. An association of s-α-klotho with eGFR was observed only in the presence of close to normal, but not high, FGF-23 concentrations. Cholecalciferol treatment did not change s-α-klotho concentrations.
authors.affiliation: Clinical Research Unit (A.S., M.T.), Department of Nephrology, and Centre for Individualized Medicine in Arterial Diseases (L.P., L.M.R.), Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000 Odense C, Denmark; Institute of Clinical Research (A.S., M.T.) and Institute of Molecular Medicine (Y.L., S.X., M.T.), Cardiovascular and Renal Research, University of Southern Denmark, 5000 Odense C, Denmark; Labor Dr Limbach und Kollegen (H.J.R.), Medizinisches Versorgungszentrum, 69126 Heidelberg, Germany; and Institute of Nutritional Science (B.H.), University of Potsdam, 14558 Nuthetal/Potsdam, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Scholze
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Lise
authors.initials: L
authors.lastname: Pedersen
authors.forename: Shengqiang
authors.initials: S
authors.lastname: Xia
authors.forename: Heinz J
authors.initials: HJ
authors.lastname: Roth
authors.forename: Berthold
authors.initials: B
authors.lastname: Hocher
authors.forename: Lars Melholt
authors.initials: LM
authors.lastname: Rasmussen
authors.forename: Martin
authors.initials: M
authors.lastname: Tepel
mesh_terms: D000367:Age Factors; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate / Q000502:physiology; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: C000717427:FGF23 protein, human; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; D000469:Alkaline Phosphatase; D005966:Glucuronidase; D000090265:Klotho Proteins