title: Circulating Klotho Associates With Cardiovascular Morbidity and Mortality During Hemodialysis.
abstract: Klotho gene was identified as an aging suppressor. In animals, klotho overexpression extends life span, and defective klotho results in rapid aging and early death. The kidney is the main contributor to circulating klotho levels, and, during chronic kidney disease, renal klotho gene expression is drastically reduced in animals and humans as well.
  
  
  
  We aimed to determine the consequences of a serum klotho (seKL) defect on cardiovascular morbidity and mortality during chronic dialysis.
  
  
  
  The ARNOGENE study was designed to prospectively follow a cohort of hemodialysis patients for 2 years without specific intervention. A total of 769 patients was recruited and followed from the end of 2008 until January 2011. A total of 238 patients was analyzed due to a technical sample conservation issue with other samples.
  
  
  
  The median seKL was markedly reduced, 360.4 ng/L (interquartile range 176.5) as compared with nondialysis chronic kidney disease patients or healthy volunteers. Patients with a seKL above the first quartile (≥280 ng/L) had a significantly reduced occurrence of outcome combining cardiovascular events and cardiovascular death [odds ratio (OR) = 0.39; 0.19 to 0.78, P = 0.008] compared with patient with klotho <280 ng/L. This effect persisted (OR = 0.86; 0.76 to 0.99, P = 0.03) after adjustment on age, sex, diabetes, cardiac insufficiency, dialysis vintage, and serum hemoglobin, albumin, fibroblast growth factor-23, phosphate, and calcium.
  
  
  
  These results suggest that, during chronic hemodialysis, conservation of seKL >280 ng/L is associated with a better 2-year cardiovascular protection. Thus, a preserved klotho function supports cardiovascular protection and may represent a prognostic tool and therapeutic target for cardiovascular disease.
authors.affiliation: University Lyon, UCBL, Service de Biochimie et Biologie Moléculaire, Centre Hospitalier Lyon Sud, CarMeN, CENS, F-69495 Pierre Bénite, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Marçais
authors.affiliation: University Lyon, UCBL, CNRS Laboratoire de Biométrie et Biologie Evolutive, Service de Biostatistique, Hospices Civils de Lyon, F-69495 Pierre Bénite, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Maucort-Boulch
authors.affiliation: University Lyon, UCBL, Service de Biochimie et Biologie Moléculaire, Centre Hospitalier Lyon Sud, CarMeN, CENS, F-69495 Pierre Bénite, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Drai
authors.affiliation: University Lyon, UCBL, CNRS Laboratoire de Biométrie et Biologie Evolutive, Service de Biostatistique, Hospices Civils de Lyon, F-69495 Pierre Bénite, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Dantony
authors.affiliation: University Lyon, UCBL, Service de Biochimie et Biologie Moléculaire, Centre Hospitalier Lyon Sud, CarMeN, CENS, F-69495 Pierre Bénite, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Carlier
authors.affiliation: University Lyon, UCBL, Service de Biochimie et Biologie Moléculaire, Centre Hospitalier Lyon Sud, CarMeN, CENS, F-69495 Pierre Bénite, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Blond
authors.affiliation: Service de Néphrologie Nutrition Dialyse, Centre Hospitalier Lyon Sud, F-69495 Pierre-Bénite, France.
authors.forename: Leslie
authors.initials: L
authors.lastname: Genet
authors.affiliation: Centre de Dialyse des Eaux Claires, AGDUC, F-38000 Grenoble, France.
authors.forename: François
authors.initials: F
authors.lastname: Kuentz
authors.affiliation: Clinique Edouard Rist, F-75016 Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Lataillade
authors.affiliation: Service de Néphrologie Hémodialyse, Centre Hospitalier Ardèche Nord, F-07010 Annonay, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Legrand
authors.affiliation: Centre de Dialyse AGDUC, Centre Hospitalier Général, F-26200 Montélimar, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Moreau-Gaudry
authors.affiliation: Nephrocare, F-69110 Ste Foy-les-Lyon, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jean
authors.affiliation: University Lyon, UCBL, CarMeN, CENS, Service de Néphrologie-Nutrition-Dialyse, Centre Hospitalier Lyon Sud, F-69495 Pierre Bénite, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Fouque
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D000090265:Klotho Proteins; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods* / Q000401:mortality; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000401:mortality / Q000628:therapy*; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005966:Glucuronidase; D000090265:Klotho Proteins