title: Soluble Klotho and intact fibroblast growth factor 23 in long-term kidney transplant patients.
abstract: BACKGROUND
  Controversies exist whether disturbances in mineral and bone disorder (MBD) normalise or persist after kidney transplantation. We assessed markers of MBD in patients with well-functioning kidney transplants to minimise confounding by reduced transplant function.
  
  
  METHODS
  In this cross-sectional study, 40 patients aged ≥18 years who received a first kidney transplant more than 10 years ago were included. A well-functioning transplant was defined as an estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m(2).
  
  
  RESULTS
  Median time since transplantation was 18.3 years (inter quartile range (IQR) 12.2-26.2). Albumin-corrected serum calcium levels were above upper limit of normal in 15% of the transplanted patients, and serum phosphate levels below lower limit of normal in 31%. The median levels of intact parathyroid hormone (iPTH) and intact fibroblast growth factor 23 (iFGF23) were significantly higher than that in a group of healthy volunteers (11.3 pmol/l (IQR: 8.7-16.2) vs 4.4 pmol/l (IQR: 3.8-5.9), P<0.001 and 75.0 pg/ml (IQR: 53.3-108.0) vs 51.3 pg/ml (IQR: 36.3-67.6), P=0.004 respectively). There was a non-significant reduction in soluble Klotho (sKlotho) levels (605 pg/ml (IQR: 506-784) vs 692 pg/ml (IQR: 618-866)). When compared with a control group matched for eGFR, levels of iPTH were significantly higher (P<0.001), iFGF23 had a non-significant trend towards higher levels and sKlotho towards lower levels.
  
  
  CONCLUSIONS
  In long-term kidney transplant patients with well-functioning kidney transplants, we found inappropriately high levels of iPTH and iFGF23 consistent with a state of persistent hyperparathyroidism. We speculate that the primary defect, FGF23 resistance, has evolved in the parathyroid gland before transplantation, and persists due to long half-life of the parathyroid cells.
authors.affiliation: Departments of Internal MedicineMedical BiochemistryStavanger University Hospital, PO Box 8100, N-4068 Stavanger, NorwayDepartment of Clinical MedicineUniversity of Bergen, Bergen, Norway inger.hjoerdis.bleskestad@sus.no.
authors.forename: Inger H
authors.initials: IH
authors.lastname: Bleskestad
authors.affiliation: Departments of Internal MedicineMedical BiochemistryStavanger University Hospital, PO Box 8100, N-4068 Stavanger, NorwayDepartment of Clinical MedicineUniversity of Bergen, Bergen, Norway.
authors.forename: Inga Strand
authors.initials: IS
authors.lastname: Thorsen
authors.affiliation: Departments of Internal MedicineMedical BiochemistryStavanger University Hospital, PO Box 8100, N-4068 Stavanger, NorwayDepartment of Clinical MedicineUniversity of Bergen, Bergen, Norway.
authors.forename: Grete
authors.initials: G
authors.lastname: Jonsson
authors.affiliation: Departments of Internal MedicineMedical BiochemistryStavanger University Hospital, PO Box 8100, N-4068 Stavanger, NorwayDepartment of Clinical MedicineUniversity of Bergen, Bergen, Norway.
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Skadberg
authors.affiliation: Departments of Internal MedicineMedical BiochemistryStavanger University Hospital, PO Box 8100, N-4068 Stavanger, NorwayDepartment of Clinical MedicineUniversity of Bergen, Bergen, Norway Departments of Internal MedicineMedical BiochemistryStavanger University Hospital, PO Box 8100, N-4068 Stavanger, NorwayDepartment of Clinical MedicineUniversity of Bergen, Bergen, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Bergrem
authors.affiliation: Departments of Internal MedicineMedical BiochemistryStavanger University Hospital, PO Box 8100, N-4068 Stavanger, NorwayDepartment of Clinical MedicineUniversity of Bergen, Bergen, Norway Departments of Internal MedicineMedical BiochemistryStavanger University Hospital, PO Box 8100, N-4068 Stavanger, NorwayDepartment of Clinical MedicineUniversity of Bergen, Bergen, Norway.
authors.forename: Lasse G
authors.initials: LG
authors.lastname: Gøransson
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000097:blood / Q000503:physiopathology / Q000628:therapy; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D016030:Kidney Transplantation / Q000706:statistics & numerical data; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D007690:Polycystic Kidney Diseases / Q000097:blood / Q000503:physiopathology / Q000628:therapy; D013997:Time Factors
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins