title: Circulating α-klotho levels in CKD and relationship to progression.
abstract: BACKGROUND
  α-Klotho is reported to have protective effects against kidney injury, and its renal expression is decreased in many experimental models of kidney disease. However, circulating α-klotho levels in human chronic kidney disease (CKD) and the relationship to progression are unknown.
  
  
  METHODS
  Post hoc analysis of a prospective cohort study.
  
  
  METHODS
  243 of 301 participants from a CKD cohort at our institution between January 2006 and December 2011 were eligible for the study.
  
  
  METHODS
  Baseline α-klotho levels.
  
  
  RESULTS
  Primary outcome was the composite of doubling of baseline serum creatinine concentration, end-stage renal disease, or death. End-stage renal disease was defined as onset of treatment by renal replacement therapy.
  
  
  METHODS
  Serum α-klotho and fibroblast growth factor 23 (FGF-23) were measured using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Lower serum α-klotho levels were associated with more severe CKD stage in the cross-sectional analysis of the baseline data (P for trend < 0.001). In the adjusted multivariable linear regression model, log(α-klotho) was associated independently with estimated glomerular filtration rate (β = 0.154; P = 0.001). Cox regression analysis showed that baseline α-klotho level independently predicted the composite outcome after adjustment for age, diabetes, blood pressure, estimated glomerular filtration rate, proteinuria, parathyroid hormone level, and FGF-23 level (HR per 10-pg/mL increase, 0.96; 95% CI, 0.94-0.98; P < 0.001). When patients were categorized into 2 groups according to baseline median α-klotho value, 43 (35.2%) patients with α-klotho levels ≤396.3 pg/mL reached the primary composite outcome compared with 19 (15.7%) with α-klotho levels >396.3 pg/mL (HR, 2.03; 95% CI, 1.07-3.85; P = 0.03).
  
  
  CONCLUSIONS
  Uncontrolled dietary phosphorus intake and use of frozen samples.
  
  
  CONCLUSIONS
  This observational study showed that low circulating α-klotho levels were associated with adverse kidney disease outcome, suggesting that α-klotho is a novel biomarker for CKD progression. More data from larger prospective longitudinal studies are required to validate our findings.
authors.affiliation: Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Hyoung Rae
authors.initials: HR
authors.lastname: Kim
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Nam
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Min Woong
authors.initials: MW
authors.lastname: Kang
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Han
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Shin
authors.forename: Fa Mee
authors.initials: FM
authors.lastname: Doh
authors.forename: Hyang Mo
authors.initials: HM
authors.lastname: Koo
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Ko
authors.forename: Chan Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Hyung Jung
authors.initials: HJ
authors.lastname: Oh
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Yoo
authors.forename: Shin-Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Dae Suk
authors.initials: DS
authors.lastname: Han
authors.forename: Seung Hyeok
authors.initials: SH
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D018450:Disease Progression; 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; D007676:Kidney Failure, Chronic / Q000097:blood; D000090265:Klotho Proteins; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D003404:Creatinine; D005966:Glucuronidase; D000090265:Klotho Proteins