title: Soluble klotho and autosomal dominant polycystic kidney disease.
abstract: OBJECTIVE
  Fibroblast growth factor 23 (FGF23) levels are elevated in patients with autosomal dominant polycystic kidney disease (ADPKD) and X-linked hypophosphatemia (XLH), but only the latter is characterized by a renal phosphate wasting phenotype. This study explored potential mechanisms underlying resistance to FGF23 in ADPKD.
  
  
  METHODS
  FGF23 and klotho levels were measured, and renal phosphate transport was evaluated by calculating the ratio of the maximum rate of tubular phosphate reabsorption to GFR (TmP/GFR) in 99 ADPKD patients, 32 CKD patients, 12 XLH patients, and 20 healthy volunteers. ADPKD and CKD patients were classified by estimated GFR (CKD stage 1, ≥90 ml/min per 1.73 m(2); CKD stage 2, 60-89 ml/min per 1.73 m(2)).
  
  
  RESULTS
  ADPKD patients had 50% higher FGF23 levels than did XLH patients; TmP/GFR was near normal in most ADPKD patients and very low in XLH patients. Serum klotho levels were lowest in the ADPKD group, whereas the CKD and XLH groups and volunteers had similar levels. ADPKD patients with an apparent renal phosphate leak had two-fold higher klotho levels than those without. Serum klotho values correlated inversely with cyst volume and kidney growth.
  
  
  CONCLUSIONS
  Loss of klotho might be a consequence of cyst growth and constrain the phosphaturic effect of FGF23 in most patients with ADPKD. Normal serum klotho levels were associated with normal FGF23 biologic activity in all XLH patients and a minority of ADPKD patients. Loss of klotho and FGF23 increase appear to exceed and precede the changes that can be explained by loss of GFR in patients with ADPKD.
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: Diane
authors.initials: D
authors.lastname: Poster
authors.forename: Fabienne
authors.initials: F
authors.lastname: Krauer
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Kistler
authors.forename: Katharina
authors.initials: K
authors.lastname: Rentsch
authors.forename: Gustav
authors.initials: G
authors.lastname: Andreisek
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Wüthrich
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmid
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Serra
mesh_terms: D000328:Adult; D001692:Biological Transport; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D053098:Familial Hypophosphatemic Rickets / Q000097:blood / Q000235:genetics; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D040181:Genetic Diseases, X-Linked; D005919:Glomerular Filtration Rate; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism / Q000503:physiopathology; D000090265:Klotho Proteins; D016018:Least-Squares Analysis; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010710:Phosphates / Q000378:metabolism; D016891:Polycystic Kidney, Autosomal Dominant / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000235:genetics; D013557:Switzerland; D055815:Young Adult
chemical_list: C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins