title: Evaluation of parathyroid gland angiogenesis in chronic kidney disease associated with secondary hyperparathyroidism.
abstract: BACKGROUND
  Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease. Increased parathyroid hormone (PTH) synthesis and secretion is associated with parathyroid cell hyperplasia. The exact mechanisms involved in parathyroid gland (PTG) hyperplasia are still poorly understood. There is no available data on angiogenesis in PTG of patients with chronic kidney disease and SHPT. The aim of this study is to evaluate angiogenesis and expression of the angiogenic factors, basic fibroblastic growth factor (b-FGF) and vascular endothelial growth factor A (VEGF), in secondary PTG hyperplasia.
  
  
  METHODS
  This study was performed on formalin-fixed paraffin-embedded archival tissues of 21 SHPT glands from haemodialysis (n = 19) and kidney transplanted (n = 2) patients submitted to surgical parathyroidectomy. For control, eight normal human parathyroid glands (NPG) encountered in surgical specimens of total thyroidectomy were used. We evaluated the immunohistochemical expression of the proliferation cell marker Ki67. Angiogenesis was evaluated by immunohistochemistry staining with anti-endoglin (CD105) antibody in 21 SPH and 5 NPG by stereological analysis. Levels of b-FGF and VEGF were determined by semi-quantitative analysis in 21 SPH and 8 NPG.
  
  
  RESULTS
  The SHPT patients present a mean iPTH of 1314 +/- 750 pg/ml, a corrected serum calcium of 10.3 +/- 1.2 mg/dl and a serum phosphorus of 6.1 +/- 1.4 mg/dl. SHPT glands displayed a significantly higher immunoreactivity against Ki67, compared to NPG. With CD105, a significantly higher number and volume of microvessels were observed in SHPT compared to NPG. Both VEGF and b-FGF expression were increased in SHPT compared to NPG. Using the predefined subdivision into negative and positive only the b-FGF expression was significantly increased in the SHPT glands compared to NPG.
  
  
  CONCLUSIONS
  These results suggest that PTGs in this group of patients with SHPT have a significantly higher number of vessels expressing CD105, which has been reported to preferentially label activated endothelial cells associated with angiogenesis. SHPT glands have a significantly increased expression of b-FGF compared to NPG. VEGF-A expression is also increased in the examined SHPT glands but could be less relevant for angiogenesis.
authors.affiliation: Department of Nephrology, Hospital S. João, Al. Hernani Monteiro, 4200-319 Porto, Portugal. martinspatricia@netcabo.pt
authors.forename: Patrícia
authors.initials: P
authors.lastname: Martins
authors.forename: Fernando
authors.initials: F
authors.lastname: Schmitt
authors.forename: Henrique
authors.initials: H
authors.lastname: Almeida
authors.forename: João M
authors.initials: JM
authors.lastname: Frazão
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000071063:Endoglin; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010280:Parathyroid Glands / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D019394:Ki-67 Antigen; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2