title: Effect of Paricalcitol on FGF-23 and Klotho in Kidney Transplant Recipients.
abstract: BACKGROUND
  Paricalcitol decreases intact parathyroid hormone and the frequency of secondary hyperparathyroidism after kidney transplantation. This proof-of-concept study aimed to assess the effect of paricalcitol on fibroblast growth factor-23/KLOTHO axis in renal transplants.
  
  
  METHODS
  Twenty-nine subjects with secondary hyperparathyroidism received oral paricalcitol 1 μg/d for 3 months, and 8 patients matched by age, sex, and creatinine clearance, but with intact parathyroid hormone less than 100 pg/mL, were included as controls.
  
  
  RESULTS
  Intact parathyroid hormone decreased in paricalcitol-treated patients (P < 0.0001). Serum fibroblast growth factor-23 enhanced (P < 0.01), whereas KLOTHO concentrations showed a trend to increase (P = 0.067). KLOTHO gene expression in peripheral blood mononuclear cells increased by 45.7% in paricalcitol-treated patients (P < 0.01), without change in controls. Paricalcitol administration resulted in a median percent decrease of 56% in methylated DNA levels of KLOTHO promoter (P < 0.001). The ratio of the unmethylated/methylated KLOTHO promoter DNA did not change in controls, but it increased by 177% in paricalcitol-treated subjects (P < 0.0001). The increase in this ratio was independently associated with the change in serum KLOTHO (r = 0.55, P < 0.01) and messenger RNA expression levels (r = 0.40, P < 0.05).
  
  
  CONCLUSIONS
  Paricalcitol administration to renal transplant patients significantly reduced intact parathyroid hormone and increased fibroblast growth factor-23, with a trend to increase in serum KLOTHO. Paricalcitol-treated patients showed a decrease in the methylation of the KLOTHO promoter with an increment in the ratio of un-methyated/methylated DNA, which was associated with an increase of KLOTHO gene expression levels and serum KLOTHO concentrations. Long-term studies are needed to assess whether paricalcitol-induced increase in KLOTHO gene expression and serum concentrations may translate into beneficial clinical effects.
authors.affiliation: 1 Research Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain. 2 Nephrology Service, University Hospital de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain. 3 Clinical Biochemistry Service, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain. 4 Nephrology Service, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Donate-Correa
authors.forename: Fernando
authors.initials: F
authors.lastname: Henríquez-Palop
authors.forename: Ernesto
authors.initials: E
authors.lastname: Martín-Núñez
authors.forename: Nayra
authors.initials: N
authors.lastname: Pérez-Delgado
authors.forename: Mercedes
authors.initials: M
authors.lastname: Muros-de-Fuentes
authors.forename: Carmen
authors.initials: C
authors.lastname: Mora-Fernández
authors.forename: Juan F
authors.initials: JF
authors.lastname: Navarro-González
mesh_terms: D000368:Aged; D019175:DNA Methylation; D004872:Ergocalciferols / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005966:Glucuronidase / Q000097:blood* / Q000235:genetics; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy*; D016030:Kidney Transplantation; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011446:Prospective Studies
chemical_list: D004872:Ergocalciferols; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; C084656:paricalcitol; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins