title: Analysis of α-klotho, fibroblast growth factor-, vitamin-D and calcium-sensing receptor in 70 patients with secondary hyperparathyroidism.
abstract: OBJECTIVE
  Secondary hyperparathyroidism (sHPT) is known as a very common complication in patients with chronic kidney disease, and G-protein-coupled calcium-sensing receptor (CaSR), Vitamin D receptor (VDR) and Fibroblast growth factor receptor (FGFR)/Klotho complexes seem to be involved in its development.
  
  
  METHODS
  Hyperplastic parathyroid glands from 70 sHPT patients and normal parathyroid tissue from 7 patients were obtained during parathyroidectomy. Conventional morphological and immunohistochemical analysis of parathyroid glands was performed after dividing each slide in a 3x3 array.
  
  
  RESULTS
  The presence of lipocytes in the normal parathyroid gland and tissue architecture (nodal in patients with sHPT) allows for discrimination between normal parathyroid glands and parathyroid glands of patients with sHPT. Protein expression of Klotho, FGFR, CaSR and VDR was higher in the normal parathyroid glands compared to the sHPT group (p<0.001, p=0.07, p =0.01 and p=0.001). The variability of each protein expression within each tissue slide was high. Therefore correlations between the different immunohistochemical variables were analyzed for each of the nine fields and than analyzed for all patients. Using this analysis, a highly significant positive correlation could be found between the expression of FGFR and VDR (p=0.0004). Interestingly, in terms of VDR we found a shift to a more mixed nuclear/cytoplasmic staining in the HPT group compared to normal parathyroid gland cells, which showed solitary nuclear staining for VDR (p>0.05).
  
  
  CONCLUSIONS
  CaSR, VDR and an impaired Klotho-FGFR-axis seem to be the major players in the development of sHPT. Whether the detected correlation between FGFR and VDR and the shift to a more mixed nuclear/cytoplasmic staining of VDR will yield new insights into the pathogenesis of the disease has to be evaluated in further studies.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Robert Bosch Hospital, Stuttgart, Germany. Joerg.Latus@rbk.de
authors.forename: Joerg
authors.initials: J
authors.lastname: Latus
authors.forename: Renate
authors.initials: R
authors.lastname: Lehmann
authors.forename: Meike
authors.initials: M
authors.lastname: Roesel
authors.forename: Peter
authors.initials: P
authors.lastname: Fritz
authors.forename: Niko
authors.initials: N
authors.lastname: Braun
authors.forename: Christoph
authors.initials: C
authors.lastname: Ulmer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Steurer
authors.forename: Dagmar
authors.initials: D
authors.lastname: Biegger
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Juergen
authors.initials: J
authors.lastname: Dippon
authors.forename: M Dominik
authors.initials: MD
authors.lastname: Alscher
authors.forename: Martin
authors.initials: M
authors.lastname: Kimmel
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005966:Glucuronidase / Q000096:biosynthesis*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism* / Q000473:pathology; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000378:metabolism* / Q000473:pathology; D018167:Receptors, Calcitriol / Q000096:biosynthesis*; D044169:Receptors, Calcium-Sensing / Q000096:biosynthesis*; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis*
chemical_list: D015415:Biomarkers; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D017468:Receptors, Fibroblast Growth Factor; D005966:Glucuronidase; D000090265:Klotho Proteins