This article appears in the following NDT Plus issue: Parathyroid Intervention - Current themes and future perspectives [View the issue table of contents]
Cellular changes following direct vitamin D injection into the uraemia-induced hyperplastic parathyroid gland
1 Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke 329-0498
2 The First Department of Pathology
3 Division of Nephrology and Blood Purification Medicine, Wakayama Medical University, Wakayama 641-0012
4 Department of Nephrology, Showa University School of Medicine, Tokyo 142-0064, Japan
Correspondence: Kazuhiro Shiizaki, Division of Nephrology, Department of Internal Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. Tel: +81-285-58-7346; Fax: +81-285-44-4869; E-mail: shiizaki{at}jichi.ac.jp
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Abstract |
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Background. Hyperplasia of the parathyroid gland (PTG) is associated not only with excessive secretion of parathyroid hormone (PTH) but also with changes in the parathyroid cell (PTC) characteristics (i.e. hyperproliferative activity and low contents of vitamin D and calcium-sensing receptors). The control of PTG hyperplasia is most important in the management of secondary hyperparathyroidism (SHPT), because the advanced stage of hyperplasia is considered irreversible. For the better control of the PTH level in dialysis patients with such advanced SHPT, percutaneous vitamin D injection therapy (PDIT) under ultrasonographic guidance was developed and various cellular changes caused by this treatment were also investigated using an animal model.
Methods. The PTGs of Sprague–Dawley rats, which had been 5/6-nephrectomized and fed a high-phosphate diet, were treated with the direct injections of vitamin D agents, and cellular effects focusing the above-mentioned characters were investigated.
Results. An adequacy of the direct injection technique into the rats’ PTGs and the successful effects of this treatment in various biochemical parameters were confirmed. Such characteristics of advanced SHPT were simultaneously improved; in particular, it was confirmed that this treatment may be effective in controlling PTG hyperplasia by, at least in part, apoptosis-induced cell death.
Conclusions. A locally high level of vitamin D strongly may suppress PTH secretion and regress hyperplasia, which is involved in the induction of apoptosis in PTCs, based on the simultaneous improvements of cellular characters of advanced SHPT. The PTH control introduced by this treatment successfully ameliorated osteitis fibrosa (high bone turnover rate).
Key Words: apoptosis • Ca-sensing receptor (CaSR) • parathyroid hyperplasia • percutaneous vitamin D injection therapy (PDIT) • secondary hyperparathyroidism • vitamin D receptor (VDR)
Received for publication February 26, 2008. Accepted for publication March 7, 2008.