title: Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study.
abstract: BACKGROUND
  Klotho and fibroblast growth factor 23 (FGF23) are key regulators of mineral metabolism in renal insufficiency. FGF23 levels have been shown to increase early in chronic kidney disease (CKD); however, the corresponding soluble Klotho levels at the different CKD stages are not known.
  
  
  METHODS
  Soluble Klotho, FGF23, parathyroid hormone (PTH), 1,25-dihydroxy vitamin D(3) (1,25D) and other parameters of mineral metabolism were measured in an observational cross-sectional study in 87 patients. Locally weighted scatter plot smoothing function of these parameters were plotted versus estimated glomerular filtration rate (eGFR) to illustrate the pattern of the relationship. Linear and non-linear regression analyses were performed to estimate changes in mineral metabolism parameters per 1mL/min/1.73 m(2) decline.
  
  
  RESULTS
  In CKD 1-5, Klotho and 1,25D linearly decreased, whereas both FGF23 and PTH showed a baseline at early CKD stages and then a curvilinear increase. Crude mean Klotho level declined by 4.8 pg/mL (95% CI 3.5-6.2 pg/mL, P < 0.0001) and 1,25D levels by 0.30 ng/L (95% CI 0.18-0.41 ng/L, P < 0.0001) as GFR declined by 1 mL/min/1.73 m(2). After adjustment for age, gender, serum 25-hydroxyvitamin D levels and concomitant medications (calcium, supplemental vitamin D and calcitriol), we estimated that the mean Klotho change was 3.2 pg/mL (95% CI 1.2-5.2 pg/mL, P = 0.0019) for each 1 mL/min/1.73 m(2) GFR change. FGF23 departed from the baseline at an eGFR of 47 mL/min/1.73 m(2) (95% CI 39-56 mL/min/1.73 m(2)), whereas PTH departed at an eGFR of 34 mL/min/1.73 m(2) (95% CI 19-50 mL/min/1.73 m(2)).
  
  
  CONCLUSIONS
  Soluble Klotho and 1,25D levels decrease and FGF23 levels increase at early CKD stages, whereas PTH levels increase at more advanced CKD stages.
authors.affiliation: Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland.
authors.forename: Ivana
authors.initials: I
authors.lastname: Pavik
authors.forename: Philippe
authors.initials: P
authors.lastname: Jaeger
authors.forename: Lena
authors.initials: L
authors.lastname: Ebner
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
authors.forename: Katja
authors.initials: K
authors.lastname: Petzold
authors.forename: Daniela
authors.initials: D
authors.lastname: Spichtig
authors.forename: Diane
authors.initials: D
authors.lastname: Poster
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Wüthrich
authors.forename: Stefan
authors.initials: S
authors.lastname: Russmann
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Serra
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; 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; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D008903:Minerals / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology*; D012720:Severity of Illness Index; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D008903:Minerals; D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D002118:Calcium