title: Serum levels of soluble secreted α-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis.
abstract: BACKGROUND
  α-Klotho was first identified as an aging gene and was later shown to be a regulator of phosphate metabolism. Fibroblast growth factor 23 (FGF23) is the key regulator of phosphate metabolism. Serum levels of soluble α-Klotho in chronic kidney disease (CKD) patients have not previously been determined, especially in relation with FGF23 and creatinine levels. This study was designed to investigate whether serum soluble α-Klotho levels are modulated by renal function, age, and FGF23 level in CKD patients. This study is the first report on the utility of measuring soluble α-Klotho levels in human CKD.
  
  
  METHODS
  A total of 292 CKD patients were enrolled. Serum samples were collected, and FGF23 and soluble α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. In addition, serum creatinine, hemoglobin, albumin, calcium, and phosphate levels were measured.
  
  
  RESULTS
  Serum soluble α-Klotho levels were associated positively with estimated glomerular filtration rate (eGFR) (P < 0.0001) and inversely with serum creatinine level (P < 0.01). Interestingly, α-Klotho levels were significantly decreased in stage 2 CKD compared with stage 1 (P = 0.0001). Serum FGF23 levels were associated positively with serum creatinine and negatively with eGFR. FGF23 levels were significantly increased in stage 5 compared with stage 1 CKD. Soluble α-Klotho was associated inversely with log-transformed FGF23 level (P < 0.01).
  
  
  CONCLUSIONS
  Our data indicate that soluble α-Klotho levels are significantly decreased in stage 2 CKD compared to stage 1, and not only in the advanced stages of the disease. Soluble α-Klotho may thus represent a new biomarker for the diagnosis of CKD, especially in the early stage.
authors.affiliation: Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohashu, Oko-cho, Nankoku 783-8505, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Shimamura
authors.forename: Kazu
authors.initials: K
authors.lastname: Hamada
authors.forename: Kosuke
authors.initials: K
authors.lastname: Inoue
authors.forename: Koji
authors.initials: K
authors.lastname: Ogata
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishihara
authors.forename: Toru
authors.initials: T
authors.lastname: Kagawa
authors.forename: Mari
authors.initials: M
authors.lastname: Inoue
authors.forename: Shimpei
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Mika
authors.initials: M
authors.lastname: Ikebe
authors.forename: Kenji
authors.initials: K
authors.lastname: Yuasa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yamanaka
authors.forename: Teturo
authors.initials: T
authors.lastname: Sugiura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Terada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005919:Glomerular Filtration Rate; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood*
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins