NDT Advance Access published online on April 8, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn150
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Evaluation of parathyroid gland angiogenesis in chronic kidney disease associated with secondary hyperparathyroidism
1 Nephrology Research and Development Unit, Nephrology Department Hospital S. João 2 Institute of Molecular Pathology and Immunology of Porto University 3 Molecular and Cell Biology Laboratory, School of Medicine, Porto University, Portugal
Correspondence and offprint requests to: Patrícia Martins, Department of Nephrology, Hospital S. João, Al. Hernani Monteiro, 4200-319 Porto, Portugal. E-mail: martinspatricia{at}netcabo.pt
 |
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.
Conclusion. 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.
Keywords: angiogenesis; chronic kidney disease; parathyroid gland; secondary hyperparathyroidism
Received for publication: 29. 5.07
Accepted in revised form: 26. 2.08