2008•Clinical Kidney JournalOpen access

Cellular changes following direct vitamin D injection into the uraemia-induced hyperplastic parathyroid gland

Kazuhiro Shiizaki, Ikuji Hatamura, Shigeo Negi, Eiko Nakazawa, Ryuichi Tozawa, Shoichiro Izawa, Tadao Akizawa, Eiji Kusano

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Abstract

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).

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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).

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Available abstract

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 concepts: Medicine, Parathyroid gland, Vitamin D and neurology, Endocrinology, Internal medicine, Pathology, Parathyroid hormone, Calcium

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